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155-997: A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or double vision , halos around light, trouble with bright lights, and difficulty seeing at night . This may result in trouble driving, reading, or recognizing faces. Poor vision caused by cataracts may also result in an increased risk of falling and depression . Cataracts cause 51% of all cases of blindness and 33% of visual impairment worldwide. Cataracts are most commonly due to aging but may also occur due to trauma or radiation exposure, be present from birth , or occur following eye surgery for other problems. Risk factors include diabetes , longstanding use of corticosteroid medication, smoking tobacco , prolonged exposure to sunlight , and alcohol . The underlying mechanism involves accumulation of clumps of protein or yellow-brown pigment in

310-503: A reduction of vision . Nuclear cataracts typically cause greater impairment of distance vision than of near vision. Those with posterior subcapsular cataracts usually complain of glare as their major symptom. The severity of cataract formation, assuming no other eye disease is present, is judged primarily by a visual acuity test. Other symptoms include frequent changes of glasses and colored halos due to hydration of lens. Congenital cataracts can result in amblyopia if not treated in

465-458: A spin trapping compound caused a decrease in the level of oxidized proteins in older gerbils but did not have an effect on younger gerbils. In addition, older gerbils performed cognitive tasks better during treatment but ceased functional capacity when treatment was discontinued, causing oxidized protein levels to increase. This led researchers to conclude that oxidation of cellular proteins is potentially important for brain function. According to

620-526: A vitrectomy —without ever having had cataract surgery—will experience progression of nuclear sclerosis after the operation. This may be because the native vitreous humor is different from the solutions used to replace the vitreous (vitreous substitutes), such as BSS Plus . This may also be because the native vitreous humour contains ascorbic acid which helps neutralize oxidative damage to the lens and because conventional vitreous substitutes do not contain ascorbic acid. Accordingly, for phakic patients requiring

775-504: A better strategy for enhancing cancer cell cytotoxicity. James Watson and others have proposed that lack of intracellular ROS due to a lack of physical exercise may contribute to the malignant progression of cancer, because spikes of ROS are needed to correctly fold proteins in the endoplasmatic reticulum and low ROS levels may thus aspecifically hamper the formation of tumor suppressor proteins. Since physical exercise induces temporary spikes of ROS, this may explain why physical exercise

930-551: A biological context, ROS are byproducts of the normal metabolism of oxygen . ROS have roles in cell signaling and homeostasis . ROS are intrinsic to cellular functioning, and are present at low and stationary levels in normal cells. In plants, ROS are involved in metabolic processes related to photoprotection and tolerance to various types of stress. However, ROS can cause irreversible damage to DNA as they oxidize and modify some cellular components and prevent them from performing their original functions. This suggests that ROS has

1085-460: A broad range of microbes including Salmonella enterica , Staphylococcus aureus , Serratia marcescens , and Aspergillus spp. Studies on the homeostasis of the Drosophila melanogaster ' s intestines have shown the production of ROS as a key component of the immune response in the gut of the fly. ROS acts both as a bactericide, damaging the bacterial DNA, RNA and proteins, as well as

1240-500: A constant flow of fluid from the anterior/posterior poles of the lens and out of the equatorial regions, a dynamic that is maintained by the Na /K -ATPase pumps located in the equatorially positioned cells of the lens epithelium. The interaction of these pumps with water channels into cells called aquaporins, molecules less than 100 daltons in size among cells via gap junctions, and calcium using transporters/regulators (TRPV channels) results in

1395-483: A corrected vision of 20/40 or better after surgery. Several recent evaluations found that cataract surgery can meet expectations only when significant functional impairment due to cataracts exists before surgery. Visual function estimates such as VF-14 have been found to give more realistic estimates than visual acuity testing alone. In some developed countries, a trend to overuse cataract surgery has been noted, which may lead to disappointing results. Phacoemulsification

1550-423: A correlation seen between excessive amounts of ROS leading to apoptosis. The depolarization of the mitochondrial membrane is also characteristic of the initiation of autophagy. When mitochondria are damaged and begin to release ROS, autophagy is initiated to dispose of the damaging organelle. If a drug targets mitochondria and creates ROS, autophagy may dispose of so many mitochondria and other damaged organelles that

1705-720: A dual role; whether they will act as harmful, protective or signaling factors depends on the balance between ROS production and disposal at the right time and place. In other words, oxygen toxicity can arise both from uncontrolled production and from the inefficient elimination of ROS by the antioxidant system. ROS were also demonstrated to modify the visual appearance of fish . This potentially affects their behavior and ecology, such as their temperature control, their visual communication, their reproduction and survival. During times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. Cumulatively, this

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1860-807: A flow of nutrients throughout the lens. Glucose is the primary energy source for the lens. As mature lens fibers do not have mitochondria , approximately 80% of the glucose is metabolized via anaerobic metabolism . The remaining fraction of glucose is shunted primarily down the pentose phosphate pathway . The lack of aerobic respiration means that the lens consumes very little oxygen. Reactive oxygen species In chemistry and biology , reactive oxygen species ( ROS ) are highly reactive chemicals formed from diatomic oxygen ( O 2 ), water , and hydrogen peroxide . Some prominent ROS are hydroperoxide (O 2 H), superoxide (O 2 ), hydroxyl radical (OH ), and singlet oxygen . ROS are pervasive because they are readily produced from O 2 , which

2015-430: A large incision while pressure is applied to the vitreous membrane . The surgery has a high rate of complications. The postoperative recovery period (after removing the cataract) is usually short. The patient is usually ambulatory on the day of surgery, but is advised to move cautiously and avoid straining or heavy lifting for about a month. The eye is usually patched on the day of surgery and use of an eye shield at night

2170-418: A layering in the lens that may allow for different refractive plans within it. The refractive index of human lens varies from approximately 1.406 in the central layers down to 1.386 in less dense layers of the lens. This index gradient enhances the optical power of the lens. As more is learned about mammalian lens structure from in situ Scheimpflug photography , MRI and physiological investigations it

2325-407: A lens (a condition known as aphakia ) perceive ultraviolet light as whitish blue or whitish-violet. The lens is metabolically active and requires nourishment in order to maintain its growth and transparency. Compared to other tissues in the eye, however, the lens has considerably lower energy demands. By nine weeks into human development, the lens is surrounded and nourished by a net of vessels,

2480-509: A mature cataract, all the lens protein is opaque. In a hypermature or Morgagnian cataract, the lens proteins have become liquid. Congenital cataract, which may be detected in adulthood, has a different classification and includes lamellar, polar, and sutural cataracts. Cataracts can be classified by using the lens opacities classification system LOCS III. In this system, cataracts are classified based on type as nuclear, cortical, or posterior. The cataracts are further classified based on severity on

2635-486: A methyl group can be added, by a DNA methyltransferase , to the 5th carbon of cytosine to form 5mC (see red methyl group added to form 5mC near the top of the first figure). The DNA methyltransferases most often form 5mC within the dinucleotide sequence "cytosine-phosphate-guanine" to form 5mCpG. This addition is a major type of epigenetic alteration and it can silence gene expression . Methylated cytosine can also be demethylated , an epigenetic alteration that can increase

2790-423: A model for land based vertebrates that was not well received. The theory allows mathematical modeling to more accurately reflect the way the lens focuses while also taking into account the complexities in the suspensory ligaments and the presence of radial as well as circular muscles in the ciliary body. In this model the ligaments may pull to varying degrees on the lens at the equator using the radial muscles while

2945-426: A muscle projects from a vascular structure in the floor of the eye, called the falciform process , and serves to pull the lens backwards from the relaxed position to focus on distant objects. While amphibians move the lens forward, as do cartilaginous fish, the muscles involved are not similar in either type of animal. In frogs , there are two muscles, one above and one below the lens, while other amphibians have only

3100-465: A needle-shaped instrument, Galen attempted to remove the cataract-affected lens of the eye. Muslim ophthalmologist Ammar Al-Mawsili , in his The Book of Choice in Ophthalmology , written circa 1000 CE, wrote of his invention of a syringe and the technique of cataract extraction while experimenting with it on a patient. In 1468 Abiathar Crescas , a Jewish physician and astrologer of

3255-468: A rat model of premature aging found increased oxidative stress , reduced antioxidant enzyme activity and substantially greater DNA damage in the brain neocortex and hippocampus of the prematurely aged rats than in normally aging control rats. The DNA damage 8-OHdG is a product of ROS interaction with DNA. Numerous studies have shown that 8-OHdG increases with age (see DNA damage theory of aging ). ROS are constantly generated and eliminated in

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3410-423: A result, production of NADPH is greatly enhanced, which functions as a cofactor to provide reducing power in many enzymatic reactions for macromolecular biosynthesis and at the same time rescuing the cells from excessive ROS produced during rapid proliferation. Cells counterbalance the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX), which rely on

3565-446: A scale from 1 to 5. The LOCS III system is highly reproducible. Risk factors such as UVB exposure and smoking can be addressed. Although no means of preventing cataracts has been scientifically proven, wearing sunglasses that block ultraviolet light may slow their development. While adequate intake of vitamins A , C , and E may protect against the risk of cataracts, clinical trials have shown no benefit from supplements, although

3720-559: A signalling molecule that induces repair mechanisms of the epithelium . The uracil released by microorganism triggers the production and activity of DUOX, the ROS-producing enzyme in the intestine. DUOX activity is induced according to the level of uracil in the gut; under basal conditions, it is down-regulated by the protein kinase MkP3 . The tight regulation of DUOX avoids excessive production of ROS and facilitates differentiation between benign and damage-inducing microorganisms in

3875-533: A single cell. 8-oxoguanine is the most abundant among various oxidized nitrogeneous bases observed. During DNA replication, DNA polymerase mispairs 8-oxoguanine with adenine, leading to a G→T transversion mutation. The resulting genomic instability directly contributes to carcinogenesis. Cellular transformation leads to cancer and interaction of atypical PKC-ζ isoform with p47phox controls ROS production and transformation from apoptotic cancer stem cells through blebbishield emergency program . Uncontrolled proliferation

4030-413: A smooth, transparent basement membrane that completely surrounds the lens. The capsule is elastic and its main structural component is collagen . It is presumed to be synthesized by the lens epithelium and its main components in order of abundance are heparan sulfate proteoglycan (sulfated glycosaminoglycans (GAGs)), entactin , type IV collagen and laminin . The capsule is very elastic and so allows

4185-435: A sphere of cells formed by budding of the inner embryo layers comes close to the embyro's outer skin. The sphere of cells induces nearby outer skin to start changing into the lens placode . The lens placode is the first stage of transformation of a patch of skin into the lens. At this early stage, the lens placode is a single layer of cells . As development progresses, the lens placode begins to deepen and bow inwards. As

4340-441: A timely manner. Age is the most common cause of cataracts. Lens proteins denature and degrade over time, and this process is accelerated by diseases such as diabetes mellitus and hypertension . Environmental factors, including toxins, radiation, and ultraviolet light have cumulative effects which are worsened by the loss of protective and restorative mechanisms due to alterations in gene expression and chemical processes within

4495-453: A variety of inflammatory responses including cardiovascular disease . They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels , in ototoxicity of drugs such as cisplatin , and in congenital deafness in both animals and humans. ROS are also implicated in mediation of apoptosis or programmed cell death and ischaemic injury. Specific examples include stroke and heart attack . In general,

4650-428: A vitrectomy it is becoming increasingly common for ophthalmologists to offer the vitrectomy combined with prophylactic cataract surgery to prevent cataract formation. Hyperbaric oxygen therapy (HBOT) is the administration of 100% oxygen at pressures greater than one-atmosphere absolute pressure (1 ATA) for a therapeutic purpose. HBOT can have several side effects, including the long-term development of cataracts. This

4805-401: A younger human lens in its natural environment is approximately 18 dioptres , roughly one-third of the eye's total power of about 60 dioptres. By 25 years of age the ability of the lens to alter the light path has reduced to 10 dioptres and accommodation continues to decline with age. The lens is located towards the front part of the vertebrate eye, called the anterior segment , which includes

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4960-413: Is hydrogen peroxide (H 2 O 2 ), which is converted from superoxide that leaks from the mitochondria. Catalase and superoxide dismutase ameliorate the damaging effects of hydrogen peroxide and superoxide, respectively, by converting these compounds into oxygen and hydrogen peroxide (which is later converted to water), resulting in the production of benign molecules . However, this conversion

5115-407: Is a condition in which months or years after successful cataract surgery, vision deteriorates or problems with glare and light scattering recur, usually due to thickening of the back or posterior capsule surrounding the implanted lens, so-called 'posterior lens capsule opacification'. Growth of natural lens cells remaining after the natural lens was removed may be the cause, and the younger the patient,

5270-458: Is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction, as demonstrated in a study in which old rats were given mitochondrial metabolites and then given cognitive tests . Results showed that the rats performed better after receiving the metabolites, suggesting that the metabolites reduced oxidative damage and improved mitochondrial function. Accumulating oxidative damage can then affect

5425-501: Is a double-edged sword. On one hand, at low levels, ROS facilitates cancer cell survival since cell-cycle progression driven by growth factors and receptor tyrosine kinases (RTK) require ROS for activation and chronic inflammation, a major mediator of cancer, is regulated by ROS. On the other hand, a high level of ROS can suppress tumor growth through the sustained activation of cell-cycle inhibitor and induction of cell death as well as senescence by damaging macromolecules. In fact, most of

5580-584: Is a driving force behind apoptosis, but in even higher amounts, ROS can result in both apoptosis and necrosis, a form of uncontrolled cell death, in cancer cells. Numerous studies have shown the pathways and associations between ROS levels and apoptosis, but a newer line of study has connected ROS levels and autophagy. ROS can also induce cell death through autophagy, which is a self-catabolic process involving sequestration of cytoplasmic contents (exhausted or damaged organelles and protein aggregates) for degradation in lysosomes. Therefore, autophagy can also regulate

5735-820: Is a hallmark of cancer cells. Both exogenous and endogenous ROS have been shown to enhance proliferation of cancer cells. The role of ROS in promoting tumor proliferation is further supported by the observation that agents with potential to inhibit ROS generation can also inhibit cancer cell proliferation. Although ROS can promote tumor cell proliferation, a great increase in ROS has been associated with reduced cancer cell proliferation by induction of G2/M cell cycle arrest; increased phosphorylation of ataxia telangiectasia mutated (ATM), checkpoint kinase 1 (Chk 1), Chk 2; and reduced cell division cycle 25 homolog c (CDC25). A cancer cell can die in three ways: apoptosis , necrosis , and autophagy . Excessive ROS can induce apoptosis through both

5890-596: Is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O 2 , which is central to fuel cells . ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations. ROS are not uniformly defined. All sources include superoxide, singlet oxygen, and hydroxyl radical. Hydrogen peroxide

6045-454: Is also known as the caspase cascade and is induced through mitochondrial damage which triggers the release of cytochrome c. DNA damage, oxidative stress, and loss of mitochondrial membrane potential lead to the release of the pro-apoptotic proteins mentioned above stimulating apoptosis. Mitochondrial damage is closely linked to apoptosis and since mitochondria are easily targeted there is potential for cancer therapy. The cytotoxic nature of ROS

6200-656: Is an autosomal recessive disorder associated with cuneiform cataracts and nuclear sclerosis. Basal-cell nevus and pemphigus have similar associations. Cigarette smoking has been shown to increase the risk of age-related cataract and nuclear cataract. Evidence is conflicting over the effect of alcohol. Some surveys have shown a link, but others that followed people over longer terms have not. Low vitamin C intake and serum levels have been associated with greater cataract rates. However, use of supplements of vitamin C has not demonstrated benefit. Some medications, such as systemic, topical, or inhaled corticosteroids , may increase

6355-630: Is an overall increase in endogenous ROS, which when above a cellular tolerability threshold, may induce cell death. On the other hand, normal cells appear to have, under lower basal stress and reserve, a higher capacity to cope with additional ROS-generating insults than cancer cells do. Therefore, the elevation of ROS in all cells can be used to achieve the selective killing of cancer cells. Radiotherapy also relies on ROS toxicity to eradicate tumor cells. Radiotherapy uses X-rays, γ-rays as well as heavy particle radiation such as protons and neutrons to induce ROS-mediated cell death and mitotic failure. Due to

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6510-460: Is associated only with infection by non-virulent pathogens and is an induced response dependent on increased mRNA transcription encoding enzymes. Superoxide dismutases (SOD) are a class of enzymes that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen. In mammals and most chordates, three forms of superoxide dismutase are present. SOD1

6665-457: Is becoming apparent the lens itself is not responding entirely passively to the surrounding ciliary muscle but may be able to change its overall refractive index through mechanisms involving water dynamics in the lens still to be clarified. The accompanying micrograph shows wrinkled fibers from a relaxed sheep lens after it is removed from the animal indicating shortening of the lens fibers during near focus accommodation. The age related changes in

6820-442: Is beneficial for cancer patient prognosis. Moreover, high inducers of ROS such as 2-deoxy-D-glucose and carbohydrate-based inducers of cellular stress induce cancer cell death more potently because they exploit the cancer cell's high avidity for sugars. ROS are critical in memory formation. ROS also have a central role in epigenetic DNA demethylation , which is relevant to learning and memory In mammalian nuclear DNA,

6975-441: Is commonly co-observed. Thus, once a more in-depth understanding of autophagic cell death is attained and its relation to ROS, this form of programmed cell death may serve as a future cancer therapy. Autophagy and apoptosis are distinct mechanisms for cell death brought on by high levels of ROS. Aautophagy and apoptosis, however, rarely act through strictly independent pathways. There is a clear connection between ROS and autophagy and

7130-451: Is extremely reactive and immediately removes electrons from any molecule in its path, turning that molecule into a free radical and thus propagating a chain reaction. However, hydrogen peroxide is actually more damaging to DNA than the hydroxyl radical, since the lower reactivity of hydrogen peroxide provides enough time for the molecule to travel into the nucleus of the cell, subsequently reacting with macromolecules such as DNA. In plants,

7285-404: Is generated from PSII, instead of PSI; QB is shown as the location for the generation of O 2 •-. The formation of ROS can be stimulated by a variety of agents such as pollutants, heavy metals , tobacco , smoke, drugs, xenobiotics , microplastics , or radiation. In plants, in addition to the action of dry abiotic factors , high temperature, interaction with other living beings can influence

7440-465: Is known as oxidative stress . The production of ROS is strongly influenced by stress factor responses in plants, these factors that increase ROS production include drought, salinity, chilling, defense of pathogens, nutrient deficiency, metal toxicity and UV-B radiation. ROS are also generated by exogenous sources such as ionizing radiation generating irreversible effects in the development of tissues in both animals and plants. ROS are produced during

7595-405: Is less curved than the back. In a human adult, the lens is typically about 10mm in diameter and 4mm thick, though its shape changes with accommodation and its size grows throughout a person's lifetime. The lens has three main parts: the lens capsule , the lens epithelium, and the lens fibers. The lens capsule is a relatively thick basement membrane forming the outermost layer of the lens. Inside

7750-454: Is located primarily in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first is a dimer (consists of two units), while the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc ions, while SOD2 has a manganese ion in its reactive centre. The genes are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1). The SOD-catalysed dismutation of superoxide may be written with

7905-532: Is made here of the convergent evolution of vertebrate and Molluscan eyes . The most complex Molluscan eye is the Cephalopod eye which is superficially similar structure and function to a vertebrate eye, including accommodation, while differing in basic ways such as having a two part lens and no cornea. The fundamental requirements of optics must be filled by all eyes with lenses using the tissues at their disposal so superficially eyes all tend to look similar. It

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8060-474: Is not 100% efficient, and residual peroxides persist in the cell. While ROS are produced as a product of normal cellular functioning, excessive amounts can cause deleterious effects. Memory capabilities decline with age, evident in human degenerative diseases such as Alzheimer's disease , which is accompanied by an accumulation of oxidative damage. Current studies demonstrate that the accumulation of ROS can decrease an organism's fitness because oxidative damage

8215-429: Is not nearly as reactive as these species, but is readily activated and is thus included. Peroxynitrite and nitric oxide are reactive oxygen-containing species as well. In its fleeting existence, the hydroxyl radical reacts rapidly irreversibly with all organic compounds. Competing with its formation, superoxide is destroyed by the action of superoxide dismutases , enzymes that catalyze its disproportionation: In

8370-421: Is often suggested for several days after surgery. In all types of surgery, the cataractous lens is removed and replaced with an artificial lens, known as an intraocular lens , which stays in the eye permanently. Intraocular lenses are usually monofocal, correcting for either distance or near vision. Multifocal lenses may be implanted to improve near and distance vision simultaneously, but these lenses may increase

8525-448: Is present in mitochondria, a cell undergoes apoptosis or programmed cell death. In addition, ROS are produced in immune cell signaling via the NOX pathway. Phagocytic cells such as neutrophils , eosinophils , and mononuclear phagocytes produce ROS when stimulated. In chloroplasts , the carboxylation and oxygenation reactions catalyzed by rubisco ensure that the functioning of

8680-553: Is rare and generally associated with multiple HBOT exposures over a long period. As it does not usually become symptomatic during HBOT, it may often go unrecognised and is probably under-reported. Evidence is emerging that lifetime dosage of oxygen may be a precipitating factor in the development of age-related cataracts. Nuclear cataracts have been hypothesized to be the end stage of the far better known phenomenon of hyperbaric myopic shift. Cataracts may be partial or complete, stationary or progressive, hard or soft. Histologically,

8835-445: Is shown by micro-injection to form a stratified syncytium in whole lens cultures. Development of the vertebrate lens begins when the human embryo is about 4mm long. The accompanying picture shows the process in a more easily studied chicken embryo. Unlike the rest of the eye which is derived mostly from the inner embryo layers , the lens is derived from the skin around the embryo . The first stage of lens formation takes place when

8990-431: Is the most widely used cataract surgery in the developed world. This procedure uses ultrasonic energy to emulsify the cataract lens. Phacoemulsification typically comprises six steps: A Cochrane review found little to no difference in visual acuity as a function of the size of incisions made for phacoemulsification in the range from ≤ 1.5 mm to 3.0 mm. Extracapsular cataract extraction (ECCE) consists of removing

9145-551: Is the only effective treatment. Cataract surgery is not readily available in many countries, and surgery is needed only if the cataracts are causing problems and generally results in an improved quality of life . About 20 million people worldwide are blind due to cataracts. It is the cause of approximately 5% of blindness in the United States and nearly 60% of blindness in parts of Africa and South America. Blindness from cataracts occurs in about 10 to 40 per 100,000 children in

9300-422: Is the way optical requirements are met using different cell types and structural mechanisms that varies among animals. Crystallins are water-soluble proteins that compose over 90% of the protein within the lens. The three main crystallin types found in the human eye are α-, β-, and γ-crystallins. Crystallins tend to form soluble, high-molecular weight aggregates that pack tightly in lens fibers, thus increasing

9455-581: The Crown of Aragon , famously removed the cataracts of King John II of Aragon , restoring his eyesight. "Cataract" is derived from the Latin cataracta , meaning "waterfall", and from the Ancient Greek καταρράκτης ( katarrhaktēs ), "down-rushing", from καταράσσω ( katarassō ) meaning "to dash down" (from kata -, "down"; arassein , "to strike, dash"). As rapidly running water turns white, so

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9610-447: The Wnt signaling components BCL9 and Pygo2 . The whole process of differentiation of the epithelial cells into crystallin filled fiber cells without organelles occurs within the confines of the lens capsule. Older cells cannot be shed and are instead internalized towards the center of the lens. This process results in a complete temporally layered record of the differentiation process from

9765-500: The cornea and iris positioned in front of the lens. The lens is held in place by the suspensory ligaments (Zonule of Zinn) , attaching the lens at its equator to the rest of the eye through the ciliary body . Behind the lens is the jelly-like vitreous body which helps hold the lens in place. At the front of the lens is the liquid aqueous humor which bathes the lens with nutrients and other things. Land vertebrate lenses usually have an ellipsoid , biconvex shape. The front surface

9920-516: The developing world , and 1 to 4 per 100,000 children in the developed world . Cataracts become more common with age . In the United States, cataracts occur in 68% of those over the age of 80 years. Additionally they are more common in women, and less common in Hispanic and Black people. Signs and symptoms vary depending on the type of cataract, though considerable overlap occurs. People with nuclear sclerotic or brunescent cataracts often notice

10075-445: The electron transport chain . In the electron transport chain, electrons are passed through a series of proteins via oxidation-reduction reactions, with each acceptor protein along the chain having a greater reduction potential than the previous. The last destination for an electron along this chain is an oxygen molecule. In normal conditions, the oxygen is reduced to produce water; however, in about 0.1–2% of electrons passing through

10230-420: The free radical theory of aging , oxidative damage initiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. While studies in invertebrate models indicate that animals genetically engineered to lack specific antioxidant enzymes (such as SOD), in general, show a shortened lifespan (as one would expect from the theory), the converse manipulation, increasing

10385-466: The tunica vasculosa lentis , which is derived from the hyaloid artery . Beginning in the fourth month of development, the hyaloid artery and its related vasculature begin to atrophy and completely disappear by birth. In the postnatal eye, Cloquet's canal marks the former location of the hyaloid artery. After regression of the hyaloid artery, the lens receives all its nourishment from the aqueous humor. Nutrients diffuse in and waste diffuses out through

10540-574: The DNA of lens cells. Ultraviolet light, specifically UVB , has also been shown to cause cataracts, and some evidence indicates sunglasses worn at an early age can slow its development in later life. Microwaves , a type of nonionizing radiation , may cause harm by denaturing protective enzymes (e.g., glutathione peroxidase ), by oxidizing protein thiol groups (causing protein aggregation ), or by damaging lens cells via thermoelastic expansion. The protein coagulation caused by electric and heat injuries whitens

10695-515: The Na /K -ATPases keeps water and current flowing through the lens from the poles and exiting through the equatorial regions. The cells of the lens epithelium also divide into new lens fibers at the lens equator. The lens lays down fibers from when it first forms in embryo until death. The lens fibers form the bulk of the lens. They are long, thin, transparent cells, firmly packed, with diameters typically 4–7 micrometres and lengths of up to 12mm long in humans. The lens fibers stretch lengthwise from

10850-415: The advent of other ways of looking at cellular structures of lenses while still in the living animal it became apparent that regions of fiber cells, at least at the lens anterior, contain large voids and vacuoles. These are speculated to be involved in lens transport systems linking the surface of the lens to deeper regions. Very similar looking structures also indicate cell fusion in the lens. The cell fusion

11005-509: The ages of 75 and 85. Cataracts affect nearly 22 million Americans age 40 and older. By age 80, more than half of all Americans have cataracts. Direct medical costs for cataract treatment are estimated at $ 6.8 billion annually. In the eastern Mediterranean region, cataracts are responsible for over 51% of blindness. Access to eye care in many countries in this region is limited. Childhood-related cataracts are responsible for 5–20% of world childhood blindness. Vision loss due to cataracts increases

11160-433: The appearance is similar to white spokes of a wheel. Symptoms often include problems with glare and light scatter at night. Posterior subcapsular cataracts are cloudy at the back of the lens adjacent to the capsule (or bag) in which the lens sits. Because light becomes more focused toward the back of the lens, they can cause disproportionate symptoms for their size. An immature cataract has some transparent protein, but with

11315-428: The benefit of many later discoveries and techniques. Membrane proteins such as aquaporins which allow water to flow into and out of cells are the most abundant membrane protein in the lens. Connexins which allow electrical coupling of cells are also prevalent. Electron microscopy and immunofluorescent microscopy show fiber cells to be highly variable in structure and composition. Magnetic resonance imaging confirms

11470-550: The biological system and are required to drive regulatory pathways. Under normal physiological conditions, cells control ROS levels by balancing the generation of ROS with their elimination by scavenging systems. But under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids and DNA, leading to fatal lesions in the cell that contribute to carcinogenesis. Cancer cells exhibit greater ROS stress than normal cells do, partly due to oncogenic stimulation, increased metabolic activity and mitochondrial malfunction. ROS

11625-425: The capsule, much thinner lens fibers form the bulk of the lens. The cells of the lens epithelium form a thin layer between the lens capsule and the outermost layer of lens fibers at the front of the lens but not the back. The lens itself lacks nerves, blood vessels, or connective tissue. Anatomists will often refer to positions of structures in the lens by describing it like a globe of the world. The front and back of

11780-494: The case of neurofibromatosis type 2 , juvenile cataract on one or both sides may be noted. Examples of single-gene disorder include Alport's syndrome , Conradi's syndrome , cerebrotendineous xanthomatosis , myotonic dystrophy , and oculocerebrorenal syndrome or Lowe syndrome . The skin and the lens have the same embryological origin and so can be affected by similar diseases. Those with atopic dermatitis and eczema occasionally develop shield ulcer cataracts. Ichthyosis

11935-580: The cell is no longer viable. The extensive amount of ROS and mitochondrial damage may also signal for apoptosis. The balance of autophagy within the cell and the crosstalk between autophagy and apoptosis mediated by ROS is crucial for a cell's survival. This crosstalk and connection between autophagy and apoptosis could be a mechanism targeted by cancer therapies or used in combination therapies for highly resistant cancers. After growth factor stimulation of RTKs, ROS can trigger activation of signaling pathways involved in cell migration and invasion such as members of

12090-413: The cell wall. This prevents the spread of the pathogen to other parts of the plant, essentially forming a net around the pathogen to restrict movement and reproduction. In the mammalian host, ROS is induced as an antimicrobial defense. To highlight the importance of this defense, individuals with chronic granulomatous disease who have deficiencies in generating ROS, are highly susceptible to infection by

12245-515: The cell's health in times of oxidative stress. Autophagy can be induced by ROS levels through many pathways in the cell in an attempt to dispose of harmful organelles and prevent damage, such as carcinogens, without inducing apoptosis. Autophagic cell death can be prompted by the over expression of autophagy where the cell digests too much of itself in an attempt to minimize the damage and can no longer survive. When this type of cell death occurs, an increase or loss of control of autophagy regulating genes

12400-448: The cells that resemble "ball and socket" forms. The lens is split into regions depending on the age of the lens fibers of a particular layer. Moving outwards from the central, oldest layer, the lens is split into an embryonic nucleus, the fetal nucleus, the adult nucleus, the inner and outer cortex. New lens fibers, generated from the lens epithelium, are added to the outer cortex. Mature lens fibers have no organelles or nuclei . With

12555-403: The chain (this number derives from studies in isolated mitochondria, though the exact rate in live organisms is yet to be fully agreed upon), oxygen is instead prematurely and incompletely reduced to give the superoxide radical ( O 2 ), most well documented for Complex I and Complex III . Another source of ROS production in animal cells is the electron transfer reactions catalyzed by

12710-411: The chance of unsatisfactory vision. Serious complications of cataract surgery include retinal detachment and endophthalmitis . In both cases, patients notice a sudden decrease in vision. In endophthalmitis, patients often describe pain. Retinal detachment frequently presents with unilateral visual field defects, blurring of vision, flashes of light, or floating spots. The risk of retinal detachment

12865-529: The chemotherapeutic and radiotherapeutic agents kill cancer cells by augmenting ROS stress. The ability of cancer cells to distinguish between ROS as a survival or apoptotic signal is controlled by the dosage, duration, type, and site of ROS production. Modest levels of ROS are required for cancer cells to survive, whereas excessive levels kill them. Metabolic adaptation in tumours balances the cells' need for energy with equally important need for macromolecular building blocks and tighter control of redox balance. As

13020-426: The dual role of ROS, both prooxidant and antioxidant-based anticancer agents have been developed. However, modulation of ROS signaling alone seems not to be an ideal approach due to adaptation of cancer cells to ROS stress, redundant pathways for supporting cancer growth and toxicity from ROS-generating anticancer drugs. Combinations of ROS-generating drugs with pharmaceuticals that can break the redox adaptation could be

13175-486: The efficiency of mitochondria and further increase the rate of ROS production. The accumulation of oxidative damage and its implications for aging depends on the particular tissue type where the damage is occurring. Additional experimental results suggest that oxidative damage is responsible for age-related decline in brain functioning. Older gerbils were found to have higher levels of oxidized protein in comparison to younger gerbils. Treatment of old and young mice with

13330-571: The electron transport chain (ETC) occurs in an environment rich in O 2 . The leakage of electrons in the ETC will inevitably produce ROS within the chloroplasts. ETC in photosystem I (PSI) was once believed to be the only source of ROS in chloroplasts. The flow of electrons from the excited reaction centers is directed to the NADP and these are reduced to NADPH, and then they enter the Calvin cycle and reduce

13485-474: The energy needed to fuel biological functions is produced in the mitochondria via the electron transport chain . Reactive oxygen species (ROS) with the potential to cause cellular damage are produced along with the release of energy. ROS can damage lipids, DNA , RNA , and proteins, which, in theory, contributes to the physiology of aging . ROS are produced as a normal product of cellular metabolism . In particular, one major contributor to oxidative damage

13640-506: The energy of the reactive peroxides to a sulfur-containing tripeptide called glutathione . The sulfur contained in these enzymes acts as the reactive center, carrying reactive electrons from the peroxide to the glutathione. Peroxiredoxins also degrade H 2 O 2 , within the mitochondria, cytosol, and nucleus. Effects of ROS on cell metabolism are well documented in a variety of species. These include not only roles in apoptosis (programmed cell death) but also positive effects such as

13795-451: The evidence is mixed, but weakly positive, for a potential protective effect of the carotenoids , lutein and zeaxanthin . The appropriateness of surgery depends on a person's particular functional and visual needs and other risk factors. Cataract removal can be performed at any stage and no longer requires ripening of the lens. Surgery is usually outpatient and usually performed using local anesthesia . About 9 of 10 patients can achieve

13950-453: The expression of a gene. A major enzyme involved in demethylating 5mCpG is TET1 . However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form 8-hydroxy-2'-deoxyguanosine (8-OHdG), resulting in a 5mCp-8-OHdG dinucleotide . However, TET1 is only able to act on the 5mC part of the dinucleotide when the base excision repair enzyme OGG1 binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to

14105-406: The expression of nucleus genes leading to chlorosis and programmed cell death . In cases of biotic stress, the generation of ROS occurs quickly and weakly initially and then becomes more solid and lasting. The first phase of ROS accumulation is associated with plant infection and is probably independent of the synthesis of new ROS-generating enzymes . However, the second phase of ROS accumulation

14260-614: The expression of various tumor suppressor genes such as p53, retinoblastoma gene (Rb), and phosphatase and tensin homolog (PTEN). ROS-related oxidation of DNA is one of the main causes of mutations, which can produce several types of DNA damage, including non-bulky (8-oxoguanine and formamidopyrimidine) and bulky (cyclopurine and etheno adducts) base modifications, abasic sites, non-conventional single-strand breaks, protein-DNA adducts, and intra/interstrand DNA crosslinks. It has been estimated that endogenous ROS produced via normal cell metabolism modify approximately 20,000 bases of DNA per day in

14415-579: The extrinsic and intrinsic pathways. In the extrinsic pathway of apoptosis, ROS are generated by Fas ligand as an upstream event for Fas activation via phosphorylation, which is necessary for subsequent recruitment of Fas-associated protein with death domain and caspase 8 as well as apoptosis induction. In the intrinsic pathway, ROS function to facilitate cytochrome c release by activating pore-stabilizing proteins (Bcl-2 and Bcl-xL) as well as inhibiting pore-destabilizing proteins (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer). The intrinsic pathway

14570-679: The eye and covering the eye with warm butter . References to cataracts and their treatment in Ancient Rome are also found in 29 AD in De Medicinae , the work of the Latin encyclopedist Aulus Cornelius Celsus . Archaeological evidence of eye surgery in the Roman era also exists. Galen of Pergamon (ca. 2nd century CE), a prominent Greek physician , surgeon and philosopher , performed an operation similar to modern cataract surgery. Using

14725-507: The eye. Lens (anatomy) Along with the cornea , aqueous , and vitreous humours , the lens refracts light, focusing it onto the retina . In many land animals the shape of the lens can be altered, effectively changing the focal length of the eye, enabling them to focus on objects at various distances. This adjustment of the lens is known as accommodation (see also below ). In many fully aquatic vertebrates, such as fish, other methods of accommodation are used, such as changing

14880-426: The eye. Oxidative stress associated with lipid peroxidation is an important pathogenic mechanism in cataract formation. Senile cataracts are associated with a decrease in antioxidant capacity in the lens. An increase in oxidative stress in the lens or a decrease in the ability to remove reactive oxygen species can lead to the lens becoming more opaque. Blunt trauma causes swelling, thickening, and whitening of

15035-541: The final electron acceptor, CO 2 . In cases where there is an ETC overload, part of the electron flow is diverted from ferredoxin to O 2 , forming the superoxide free radical (by the Mehler reaction ). In addition, electron leakage to O 2 can also occur from the 2Fe-2S and 4Fe-4S clusters in the PSI ETC. However, PSII also provides electron leakage locations (QA, QB) for O 2 -producing O 2 -. Superoxide (O 2 -)

15190-451: The following half-reactions: where M =  Cu ( n = 1 ); Mn ( n = 2 ); Fe ( n = 2 ); Ni ( n = 2 ). In this reaction the oxidation state of the metal cation oscillates between n and n + 1 . Catalase , which is concentrated in peroxisomes located next to mitochondria, reacts with the hydrogen peroxide to catalyze the formation of water and oxygen. Glutathione peroxidase reduces hydrogen peroxide by transferring

15345-449: The former being predominantly used. Cancer cells with elevated ROS levels depend heavily on the antioxidant defense system. ROS-elevating drugs further increase cellular ROS stress level, either by direct ROS-generation (e.g. motexafin gadolinium, elesclomol) or by agents that abrogate the inherent antioxidant system such as SOD inhibitor (e.g. ATN-224, 2-methoxyestradiol) and GSH inhibitor (e.g. PEITC, buthionine sulfoximine (BSO)). The result

15500-419: The greater the chance of this occurring. Management involves cutting a small, circular area in the posterior capsule with targeted beams of energy from a laser, called Nd:YAG laser capsulotomy, after the type of laser used. The laser can be aimed very accurately, and the small part of the capsule which is cut falls harmlessly to the bottom of the inside of the eye. This procedure leaves sufficient capsule to hold

15655-761: The gut. The manner in which ROS defends the host from invading microbe is not fully understood. One of the more likely modes of defense is damage to microbial DNA. Studies using Salmonella demonstrated that DNA repair mechanisms were required to resist killing by ROS. A role for ROS in antiviral defense mechanisms has been demonstrated via Rig-like helicase-1 and mitochondrial antiviral signaling protein. Increased levels of ROS potentiate signaling through this mitochondria-associated antiviral receptor to activate interferon regulatory factor (IRF)-3, IRF-7, and nuclear factor kappa B (NF-κB), resulting in an antiviral state. Respiratory epithelial cells induce mitochondrial ROS in response to influenza infection. This induction of ROS led to

15810-470: The harmful effects of reactive oxygen species on the cell are the damage of DNA or RNA, oxidation of polyunsaturated fatty acids in lipids ( lipid peroxidation ), oxidation of amino acids in proteins, and oxidative deactivation of specific enzymes by oxidation co-factors. When a plant recognizes an attacking pathogen, one of the first induced reactions is to rapidly produce superoxide ( O 2 ) or hydrogen peroxide ( H 2 O 2 ) to strengthen

15965-410: The highest risk group of patients, the incidence of pseudophakic retinal detachment may be as high as 20%. The risk of endophthalmitis occurring after surgery is less than one in 1000. Corneal edema and cystoid macular edema are less serious but more common, and occur because of persistent swelling at the front of the eye in corneal edema or back of the eye in cystoid macular edema. They are normally

16120-463: The human lens may also be related to changes in the water dynamics in the lens. In reptiles and birds , the ciliary body which supports the lens via suspensory ligaments also touches the lens with a number of pads on its inner surface. These pads compress and release the lens to modify its shape while focusing on objects at different distances; the suspensory ligaments usually perform this function in mammals . With vision in fish and amphibians ,

16275-496: The index of refraction of the lens while maintaining its transparency. β and γ crystallins are found primarily in the lens, while subunits of α -crystallin have been isolated from other parts of the eye and the body. α-crystallin proteins belong to a larger superfamily of molecular chaperone proteins , and so it is believed that the crystallin proteins were evolutionarily recruited from chaperone proteins for optical purposes. The chaperone functions of α-crystallin may also help maintain

16430-441: The induction of host defence genes and mobilization of ion transporters . This implicates them in control of cellular function. In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury . These also provide a link to the adaptive immune system via the recruitment of leukocytes . Reactive oxygen species are implicated in cellular activity to

16585-469: The induction of type III interferon and the induction of an antiviral state, limiting viral replication. In host defense against mycobacteria, ROS play a role, although direct killing is likely not the key mechanism; rather, ROS likely affect ROS-dependent signalling controls, such as cytokine production, autophagy, and granuloma formation. Reactive oxygen species are also implicated in activation, anergy and apoptosis of T cells . In aerobic organisms

16740-409: The leading cause of blindness. Even where surgical services are available, low vision associated with cataracts may still be prevalent as a result of long waits for, and barriers to, surgery, such as cost, lack of information and transportation problems. In the United States, age-related lens changes have been reported in 42% between the ages of 52 and 64, 60% between the ages 65 and 74, and 91% between

16895-453: The lens are referred to as the anterior and posterior "poles", like the North and South poles. The "equator" is the outer edge of the lens often hidden by the iris and is the area of most cell differentiation. As the equator is not generally in the light path of the eye, the structures involved with metabolic activity avoid scattering light that would otherwise affect vision. The lens capsule is

17050-455: The lens fibers. By providing the lens fibers with nutrients and removing waste, the cells of the epithelium maintain lens homeostasis . As ions, nutrients, and liquid enter the lens from the aqueous humor , Na /K -ATPase pumps in the lens epithelial cells pump ions out of the lens to maintain appropriate lens osmotic concentration and volume, with equatorially positioned lens epithelium cells contributing most to this current. The activity of

17205-678: The lens fibers. While the swelling normally resolves with time, the white color may remain. In severe blunt trauma, or in injuries that penetrate the eye, the capsule in which the lens sits can be damaged. This damage allows fluid from other parts of the eye to rapidly enter the lens leading to swelling and then whitening, obstructing light from reaching the retina at the back of the eye. Cataracts may develop in 0.7 to 8.0% of cases following electrical injuries . Blunt trauma can also result in star- (stellate) or petal-shaped cataracts. Cataracts can arise as an effect of exposure to various types of radiation. X-rays, one form of ionizing radiation , may damage

17360-401: The lens grows by laying down more fibers through to early adulthood, the lens becomes more ellipsoid in shape. After about age 20 the lens grows rounder again and the iris is very important for this development. Several proteins control the embryonic development of the lens though PAX6 is considered the master regulator gene of this organ. Other effectors of proper lens development include

17515-769: The lens in place, but removes enough to allow light to pass directly through to the retina. Serious side effects are rare. Posterior capsular opacification is common and occurs following up to one in four operations, but these rates are decreasing following the introduction of modern intraocular lenses together with a better understanding of the causes. Vitreous touch syndrome is a possible complication of intracapsular cataract extraction. Age-related cataracts are responsible for 51% of world blindness, about 20 million people. Globally, cataracts cause moderate to severe disability in 53.8 million (2004), 52.2 million of whom are in low and middle income countries. In many countries, surgical services are inadequate, and cataracts remain

17670-418: The lens is fixed in shape, and focusing is instead achieved by moving the lens forwards or backwards within the eye using a muscle called the retractor lentus. In cartilaginous fish , the suspensory ligaments are replaced by a membrane, including a small muscle at the underside of the lens. This muscle pulls the lens forward from its relaxed position when focusing on nearby objects. In teleosts , by contrast,

17825-414: The lens is held under tension by its suspending ligaments being pulled tight by the pressure of the eyeball. At short focal distance the ciliary muscle contracts relieving some of the tension on the ligaments, allowing the lens to elastically round up a bit, increasing refractive power. Changing focus to an object at a greater distance requires a thinner less curved lens. This is achieved by relaxing some of

17980-481: The lens is removed through a self-sealing scleral tunnel wound in the sclera which, ideally, is watertight and does not require suturing. Although "small", the incision is still markedly larger than the portal in phacoemulsification. This surgery is increasingly popular in the developing world where access to phacoemulsification is still limited. Intracapsular cataract extraction (ICCE) is rarely performed. The lens and surrounding capsule are removed in one piece through

18135-427: The lens manually, but leaving the majority of the capsule intact. The lens is expressed through a 10- to 12-mm incision which is closed with sutures at the end of surgery. ECCE is less frequently performed than phacoemulsification, but can be useful when dealing with very hard cataracts or other situations where emulsification is problematic. Manual small incision cataract surgery (MSICS) has evolved from ECCE. In MSICS,

18290-417: The lens of primates such as humans is unusually flat going some way to explain why our vision, unlike diving birds, is particularly blurry under water. In humans the widely quoted Helmholtz mechanism of focusing, also called accommodation , is often referred to as a "model". Direct experimental proof of any lens model is necessarily difficult as the vertebrate lens is transparent and only functions well in

18445-472: The lens proteins, which must last a human for their entire lifetime. Another important factor in maintaining the transparency of the lens is the absence of light-scattering organelles such as the nucleus , endoplasmic reticulum , and mitochondria within the mature lens fibers. Lens fibers also have a very extensive cytoskeleton that maintains the precise shape and packing of the lens fibers; disruptions/mutations in certain cytoskeletal elements can lead to

18600-443: The lens that reduces transmission of light to the retina at the back of the eye. Diagnosis is by an eye examination . Wearing sunglasses and a wide brimmed hat, eating leafy vegetables and fruits, and avoiding smoking may reduce the risk of developing cataracts, or slow the process. Early on, the symptoms may be improved with glasses . If this does not help, surgery to remove the cloudy lens and replace it with an artificial lens

18755-488: The lens to assume a more spherical shape when the tension of the suspensory ligaments is reduced. The human capsule varies from 2 to 28 micrometres in thickness, being thickest near the equator (peri-equatorial region) and generally thinner near the posterior pole. The photos from electron and light microscopes show an area of the capsule lens equator where the capsule grows and adjacent to where thousands of suspensory ligaments attach. Attachment must be strong enough to stop

18910-407: The lens vesicle to elongate toward the anterior end of the vesicle. These signals also induce the synthesis of proteins called crystallins . As the name suggests the crystallins can form a clear highly refractive jelly. These elongating cells eventually fill in the center of the vesicle with cells, that are long and thin like a strand of hair, called fibers. These primary fibers become the nucleus in

19065-500: The lens's position relative to the retina rather than changing the shape of the lens. Accommodation is analogous to the focusing of a photographic camera via changing its lenses . In land vertebrates the lens is flatter on its anterior side than on its posterior side, while in fish the lens is often close to spherical. Accommodation in humans is well studied and allows artificial means of supplementing our focus, such as glasses , for correction of sight as we age. The refractive power of

19220-470: The lens. In a 1911 Nobel lecture Allvar Gullstrand spoke on "How I found the intracapsular mechanism of accommodation" and this aspect of lens focusing continues to be investigated. Young spent time searching for the nerves that could stimulate the lens to contract without success. Since that time it has become clear the lens is not a simple muscle stimulated by a nerve so the 1909 Helmholtz model took precedence. Pre-twentieth century investigators did not have

19375-468: The lens. This causes a myopic shift (lenticular shift) that decreases hyperopia and enables presbyopic patients to see at near without reading glasses. This is only temporary and is called second sight. Cortical cataracts are due to the lens cortex (outer layer) becoming opaque. They occur when changes in the fluid contained in the periphery of the lens cause fissuring. When these cataracts are viewed through an ophthalmoscope , or other magnification system,

19530-578: The lens. This same process is what makes the clear albumen of an egg become white and opaque during cooking. The genetic component is strong in the development of cataracts, most commonly through mechanisms that protect and maintain the lens. The presence of cataracts in childhood or early life can occasionally be due to a particular syndrome. Examples of chromosome abnormalities associated with cataracts include 1q21.1 deletion syndrome , cri-du-chat syndrome , Down syndrome , Patau's syndrome , trisomy 18 ( Edward's syndrome ), and Turner's syndrome , and in

19685-621: The levels of antioxidant enzymes, has yielded inconsistent effects on lifespan (though some studies in Drosophila do show that lifespan can be increased by the overexpression of MnSOD or glutathione biosynthesizing enzymes). Also contrary to this theory, deletion of mitochondrial SOD2 can extend lifespan in Caenorhabditis elegans . In mice, the story is somewhat similar. Deleting antioxidant enzymes, in general, yields shorter lifespan, although overexpression studies have not (with some exceptions) consistently extended lifespan. Study of

19840-409: The ligaments being detached from the lens capsule. Forces are generated from holding the lens in place and the forces added to during focusing. While the capsule is thinnest at the equator where its area is increasing, the anterior and posterior capsule is thinner than the area of ligament attachment. The lens epithelium is a single layer of cells at the front of the lens between the lens capsule and

19995-489: The ligaments offset from the equator to the front and back are relaxed to varying degrees by contracting the circular muscles. These multiple actions operating on the elastic lens allows it to change lens shape at the front more subtly. Not only changing focus, but also correcting for lens aberrations that might otherwise result from the changing shape while better fitting mathematical modeling. The " catenary " model of lens focus proposed by Coleman demands less tension on

20150-425: The ligaments suspending the lens. Rather than the lens as a whole being stretched thinner for distance vision and allowed to relax for near focus, contraction of the circular ciliary muscles results in the lens having less hydrostatic pressure against its front. The lens front can then reform its shape between the suspensory ligaments in a similar way to a slack chain hanging between two poles might change its curve when

20305-470: The living animals. When considering all vertebrates aspects of all models may play varying roles in lens focus. The model of a shape changing lens of humans was proposed by Young in a lecture on the 27th Nov 1800. Others such as Helmholtz and Huxley refined the model in the mid-1800s explaining how the ciliary muscle contracts rounding the lens to focus near and this model was popularized by Helmholtz in 1909. The model may be summarized like this. Normally

20460-471: The loss of transparency. The lens blocks most ultraviolet light in the wavelength range of 300–400 nm; shorter wavelengths are blocked by the cornea. The pigment responsible for blocking the light is 3-hydroxykynurenine glucoside, a product of tryptophan catabolism in the lens epithelium. High intensity ultraviolet light can harm the retina, and artificial intraocular lenses are therefore manufactured to also block ultraviolet light. People lacking

20615-422: The lower muscle. In the simplest vertebrates, the lampreys and hagfish , the lens is not attached to the outer surface of the eyeball at all. There is no aqueous humor in these fish, and the vitreous body simply presses the lens against the surface of the cornea. To focus its eyes, a lamprey flattens the cornea using muscles outside of the eye and pushes the lens backwards. While not vertebrate, brief mention

20770-498: The main types of age-related cataracts are nuclear sclerosis, cortical, and posterior subcapsular. Nuclear sclerosis is the most common type of cataract, and involves the central or 'nuclear' part of the lens. This eventually becomes hard, or 'sclerotic', due to condensation on the lens nucleus and the deposition of brown pigment within the lens. In its advanced stages, it is called a brunescent cataract. In early stages, an increase in sclerosis may cause an increase in refractive index of

20925-399: The mature lens. The epithelial cells that do not form into fibers nearest the lens front give rise to the lens epithelium. Additional fibers are derived from lens epithelial cells located at the lens equator. These cells lengthen towards the front and back wrapping around fibers already laid down. The new fibers need to be longer to cover earlier fibers but as the lens gets larger the ends of

21080-460: The mitochondrial P450 systems in steroidogenic tissues. These P450 systems are dependent on the transfer of electrons from NADPH to P450. During this process, some electrons "leak" and react with O 2 producing superoxide. To cope with this natural source of ROS, the steroidogenic tissues, ovary and testis, have a large concentration of antioxidants such as vitamin C (ascorbate) and β-carotene and anti-oxidant enzymes. If too much damage

21235-532: The mitogen activated protein kinase (MAPK) family – extracellular regulated kinase (ERK), c-jun NH-2 terminal kinase (JNK) and p38 MAPK. ROS can also promote migration by augmenting phosphorylation of the focal adhesion kinase (FAK) p130Cas and paxilin. Both in vitro and in vivo, ROS have been shown to induce transcription factors and modulate signaling molecules involved in angiogenesis (MMP, VEGF) and metastasis (upregulation of AP-1, CXCR4, AKT and downregulation of PTEN). Experimental and epidemiologic research over

21390-438: The new secondary fibers being added as outer layers. New lens fibers are generated from the equatorial cells of the lens epithelium, in a region referred to as the "germinative zone" and "bow region". The lens epithelial cells elongate, lose contact with the capsule and epithelium at the back and front of the lens, synthesize crystallin , and then finally lose their nuclei (enucleate) as they become mature lens fibers. In humans, as

21545-447: The newer fibers no longer reach as far towards the front and back of the lens. The lens fibers that do not reach the poles form tight, interdigitating seams with neighboring fibers. These seams being less crystalline than the bulk of the lens are more visible and are termed "sutures". The suture patterns become more complex as more layers of lens fibers are added to the outer portion of the lens. The lens continues to grow after birth, with

21700-460: The organelle free cells at the lens exterior to the inner cells through many layers of cells. Some vertebrates need to see well both above and below water at times. One example is diving birds which have the ability to change focus by 50 to 80 dioptres. Compared with animals adapted for only one environment diving birds have a somewhat altered lens and cornea structure with focus mechanisms to allow for both environments. Even among terrestrial animals

21855-482: The past several years has indicated close associations among ROS, chronic inflammation, and cancer. ROS induces chronic inflammation by the induction of COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), IL-6), chemokines (IL-8, CXCR4) and pro-inflammatory transcription factors (NF-κB). These chemokines and chemokine receptors, in turn, promote invasion and metastasis of various tumor types. Both ROS-elevating and ROS-eliminating strategies have been developed with

22010-406: The placode continues to deepen, the opening to the surface ectoderm constricts and the lens cells bud off from the embryo's skin to form a sphere of cells known as the "lens vesicle". When the embryo is about 10mm long the lens vesicle has completely separated from the skin of the embryo. The embryo then sends signals from the developing retina, inducing the cells closest to the posterior end of

22165-423: The poles are moved closer together. This model requires fluid movement of the lens front only rather than trying to change the shape of the lens as a whole. When Thomas Young proposed the changing of the human lens's shape as the mechanism for focal accommodation in 1801 he thought the lens may be a muscle capable of contraction. This type of model is termed intracapsular accommodation as it relies on activity within

22320-473: The posterior to the anterior poles and, when cut horizontally, are arranged in concentric layers rather like the layers of an onion. If cut along the equator, cells have a hexagonal cross section, appearing as a honeycomb. The approximate middle of each fiber lies around the equator. These tightly packed layers of lens fibers are referred to as laminae. The lens fiber cytoplasms are linked together via gap junctions , intercellular bridges and interdigitations of

22475-442: The processes of respiration and photosynthesis in organelles such as mitochondria , peroxisomes and chloroplasts . During the respiration process the mitochondria convert energy for the cell into a usable form, adenosine triphosphate (ATP). The process of ATP production in the mitochondria, called oxidative phosphorylation , involves the transport of protons (hydrogen ions) across the inner mitochondrial membrane by means of

22630-403: The production of ROS occurs during events of abiotic stress that lead to a reduction or interruption of metabolic activity. For example, the increase in temperature, drought are factors that limit the availability of CO 2 due to stomatal closure, increasing the production of ROS, such as O 2 ·- and O 2 in chloroplasts. The production of O 2 in chloroplasts can cause reprogramming of

22785-586: The production of ROS. Ionizing radiation can generate damaging intermediates through the interaction with water, a process termed radiolysis . Since water comprises 55–60% of the human body, the probability of radiolysis is quite high under the presence of ionizing radiation. In the process, water loses an electron and becomes highly reactive. Then through a three-step chain reaction, water is sequentially converted to hydroxyl radical ( OH), hydrogen peroxide (H 2 O 2 ), superoxide radical ( O 2 ), and ultimately oxygen (O 2 ). The hydroxyl radical

22940-604: The reducing power of NADPH to maintain their activities. Most risk factors associated with cancer interact with cells through the generation of ROS. ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), hypoxia-inducible factor-1α and signal transducer and activator of transcription 3 (STAT3), leading to expression of proteins that control inflammation; cellular transformation; tumor cell survival; tumor cell proliferation; and invasion, angiogenesis as well as metastasis. And ROS also control

23095-418: The result of excessive inflammation following surgery, and in both cases, patients may notice blurred, foggy vision. They normally improve with time and with application of anti-inflammatory drops. The risk of either occurring is around one in 100. It is unclear whether NSAIDs or corticosteroids are superior at reducing postoperative inflammation. Posterior capsular opacification, also known as after-cataract,

23250-409: The risk of cataract development. Corticosteroids most commonly cause posterior subcapsular cataracts. People with schizophrenia often have risk factors for lens opacities (such as diabetes, hypertension, and poor nutrition). Second-generation antipsychotic medications are unlikely to contribute to cataract formation. Miotics and triparanol may increase the risk. Nearly every person who undergoes

23405-538: The risk of dementia in the elderly population, increases the likelihood of falls and road traffic accidents, and by detrimental effects on the quality of life increases mortality. Cataract surgery was first described by the Ayurvedic physician , Suśruta (about 5th century BCE) in Sushruta Samhita in ancient India . Most of the methods mentioned focus on hygiene. Follow-up treatments include bandaging of

23560-483: The sphincter like ciliary muscles. While not referenced this presumably allows the pressure in the eyeball to again expand it outwards, pulling harder on the lens making it less curved and thinner, so increasing the focal distance . There is a problem with the Helmholtz model in that despite mathematical models being tried none has come close enough to working using only the Helmholtz mechanisms. Schachar has proposed

23715-608: The start at the lens surface to the end at the lens center. The lens is therefore valuable to scientists studying the process of cell differentiation. In many aquatic vertebrates, the lens is considerably thicker, almost spherical resulting in increased light refraction. This difference helps compensate for the smaller angle of refraction between the eye's cornea and the watery environment, as they have more similar refractive indices than cornea and air. The fiber cells of fish are generally considerably thinner than those of land vertebrates and it appears crystallin proteins are transported to

23870-572: The term may have been used metaphorically to describe the similar appearance of mature ocular opacities. In Latin, cataracta had the alternative meaning " portcullis " and the name possibly passed through French to form the English meaning "eye disease" (early 15th century), on the notion of "obstruction". Early Persian physicians called the term nazul-i-ah , or "descent of the water"—vulgarised into waterfall disease or cataract—believing such blindness to be caused by an outpouring of corrupt humour into

24025-434: Was estimated as about 0.4% within 5.5 years, corresponding to a 2.3-fold risk increase compared to naturally expected incidence, with older studies reporting a substantially higher risk. The incidence is increasing over time in a somewhat linear manner, and the risk increase lasts for at least 20 years after the procedure. Particular risk factors are younger age, male sex, longer axial length, and complications during surgery. In

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