Cataract formation

If the UV radiation were to reach the surface of the earth, it could have several adverse effects. A 5% decrease in ozone concentration could increase the incidence of skin cancer by 10% to 20%. Ultraviolet radiation is also a factor in diseases of the eye, including cataract formation. 

Mutations in two genes directly lead to a disease. Mutations in the AQPO gene lead to dominantly inherited cataract. Single amino acid substitution in the AQPO gene in both mice and humans result in proteins with impaired trafficking to the plasma membrane and cataract formation, due to loss of the integrity of the lens. 

Cataract formation Ca2+ influx activates m-calpain, the predominant calpain in lens, cleaving a- and 3- but not y-crystallins. The cry stall in fragments aggregate to form cataracts39... 

Adverse reactions associated with administration of the corticosteroid ophthalmic preparations include elevated IOP with optic nerve damage, loss of visual acuity, cataract formation, delayed wound healing, secondary ocular infection, exacerbation of comeal infections, dry eyes, ptosis, blurred vision, discharge, ocular pain, foreign body sensation, and pruritus. 

R. C. Augusteyn, in Mechanisms of Cataract Formation in the Human Lens, Academic Press, New York, 1981, pp. 104-106. 

Ascorbate is known to act as a water-soluble antioxidant, reacting rapidly with superoxide, hydroxyl and peroxyl radicals. However, reduced ascorbate can react non-enzymatically with molecular oxygen to produce dehydroascorbate and hydrogen peroxide. Also, ascorbate in the presence of light, hydrogen peroxide and riboflavin, or transition metals (e.g. Fe, Cu " ), can give rise to hydroxyl radicals (Delaye and Tardieu, 1983 Ueno et al., 1987). These phenomena may also be important in oxidative damage to the lens and subsequent cataract formation. 

Primary and secondary products, and end-products of lipid peroxidation have all been shown to accumulate in senile cataracts (Babizhayev, 1989b Simonelli et al., 1989). Accumulation of these compounds in the lenticular epithelial membranes is a possible cause of damage preceding cataract formation. In senile cataracts there is also extensive oxidation of protein methionine and cysteine in both the membrane and cytosol components (Garner and Spector, 1980), while in aged normal lenses a lesser extent of oxidation was confined to the membrane. The authors therefore suggested that oxidation of membrane components was a precataract state. 

Patients in which oxidative damage may be an important aetiological factor cataract formation include those with Down s syndrome, since there is now evidence that they have increased indices of free-radical activity and lipid peroxidation. It has been su ested that this is due to the increased levels of Cu/Zn-SOD (carried on chromosome 21) generating increased concentrations of hydrogen peroxide (Bras etal., 1989). In the presence of superoxide radicals these produce highly reactive hydroxyl radicals. 

Harding, J.J. (1981). Cataract formation. In Molecular and Cellular Biology of the Lens (ed. H. Blocmdal) pp. 327-365, Wiley, New York. 

Reddy, V.N. and Giblin, F.J. (1984). Metabolism and function of glutathione in the lens. In Human Cataract Formation . Ciba Foundation Symposium 106, London, pp. 65-87. Reim, M. (1992). The results of ischemia in chemical injuries. Eye 6, 376-382. 

Spector, A. (1984). Oxidation and cataract. In Human Cataract Formation . Ciba Foundation Symposium 106, pp. 48-64. Pitman, London. 

If mast cell stabilizers or multiple-action agents are not successful, a trial of a topical NSAID is appropriate. Ketorolac is the only approved topical agent for ocular itching. NSAIDs do not mask ocular infections, affect wound healing, increase intraocular pressure, or contribute to cataract formation like the topical corticosteroids. However, for allergic conjunctivitis, topical ketorolac is not as effective as olopatadine or emedas-tine in trials.15 Full efficacy of ketorolac takes up to 2 weeks.17... 

Side effects of inhaled corticosteroids are relatively mild and include hoarseness, sore throat, oral candidiasis, and skin bruising. Severe side effects such as adrenal suppression, osteoporosis, and cataract formation are reported less frequently than with systemic corticosteroids, but clinicians should monitor patients receiving high-dose chronic inhaled therapy. 

Zhang JJ, Jacob TJC, Valverde MA, Hardy SP, Mintenig GM, Sepulveda FV, Gill DR, Hyde SC, Trezise AEO, Higgins CF (1994) Tamoxifen blocks chloride channels a possible mechanism for cataract formation. J Clin Invest 94 1690-1697... 

Rainbow trout exposed to naphthalene in surrounding water accumulate this hydrocarbon in eyes (14). The retention (including bioconversion products) may be related to observed morphological changes, such as cataract formation, which occurs in marine fish exposed to individual hydrocarbons ()8) and petroleum (19). Roubal et al. (20) have demonstrated that gills of salmonids are major sites forHischarging naphthalene, which implies that the more water-soluble hydrocarbons in general are cleared via this route. 

Which of the following enzymes is most strongly associated with cataract formation in this patient ... 

In chronic-duration toxicity studies in laboratory animals, Hollingsworth et al. (1956) found no evidence of cataract formation in rabbits administered a total of 263 doses of 500 mg/kg/day 1,4-dichlorobenzene in olive oil over a 367-day period. 

Excessive activity of the enzyme aldose reductase sometimes accompanies diabetes. The net result is often accumulation of reduced sugars such as galactose in the lens of the eye and ensuing cataract formation. A1 restatin (43), an aldose reductase inhibitor, is one of the first agents found that holds promise of preventing diabetes-induced cataracts. The compound, actually used as its sodium salt, is prepared in straightforward manner by imide formation between 1,8-naphthalic anhydride (41) and glycine. ... 

Cataracts - Lens changes also have been observed in patients taking quetiapine during long-term treatment. Examination of the lens by methods adequate to detect cataract formation, such as slit-lamp exam, is recommended at initiation of treatment or shortly thereafter, and at 6-month intervals. 

Glucocorticoids induce cataract formation, particularly in patients with rheumatoid arthritis. An increase in intraocular pressure related to a decreased outflow of aqueous humor is also a frequent side effect of periocular, topical, or systemic administration. Induction of ocular hypertension, which occurs in about 35% of the general population after glucocorticoid administration, depends on the specific drug, the dose, the frequency of administration, and the glucocorticoid responsiveness of the patient. 

Gualtieri et al., 1982 Oshika, 1995 Hansen et al., 1997). Quetiapine was reported to be associated with the development of cataracts in canine studies. For this reason, regular ophthalmic examinations are suggested for patients receiving this drug so that the possibility of cataract formation can be assessed (see Clinical Implications, below). At present, there have been no reports of a link between cataract development and quetiapine therapy in humans (Carver, 2000). 

As a general rule, ophthalmologic side effects do not appear to occur commonly in children treated with antipsychotics. Although a causal relationship between cataract formation and quetiapine treatment has not been demonstrated in adults, quetiapine administration has been noted in canine studies to lead to cataract formation. For this reason, extra ophthalmologic monitoring during chronic quetiapine treatment is recommended. 

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