Glutathione, lens

GSHPx, CAT and SOD, which normally protect cells from free-radical damage have not been detected in aqueous humour. It has therefore been su ested that damage by free radicals and hydrogen peroxide to the anterior segment is prevented by a non-enzymatic extracellular oxidoreduction system involving a constant supply of reduced glutathione to the aqueous fluid from the ciliary epithelium, cornea and lens (Riley, 1983). 

Martensson, J., Steinherz, R, Jain, A. and Meister, A. (1989). Glutathione ester prevents buthionine sulfoxamine-induced cataracts and lens epithelial damage. Proc. Natl Acad. Sci. USA 86, 8727-8731. 

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. 

Ji, X., von Rosenvinge, E.C., Johnson, W.W., Tomarev, S.I., Piadgorsky, J., Armstrong, R.N., and Gilliland, G.L. (1995) Three-dimensional structure, catalytic properties, and evolution of a sigma class glutathione transferase from squid, a progenitor of the lens S-crystallins of cephalopods. Biochemistry 34(16), 5317-5328. 

As in the case of other cardiovascular diseases, the possibility of antioxidant treatment of diabetes mellitus has been studied in both animal models and diabetic patients. The treatment of streptozotocin-induced diabetic rats with a-lipoic acid reduced superoxide production by aorta and superoxide and peroxynitrite formation by arterioles providing circulation to the region of the sciatic nerve, suppressed lipid peroxidation in serum, and improved lens glutathione level [131]. In contrast, hydroxyethyl starch desferrioxamine had no effect on the markers of oxidative stress in diabetic rats. Lipoic acid also suppressed hyperglycemia and mitochondrial superoxide generation in hearts of glucose-treated rats [132],... 

R3. Raghavachari, N., Qiao, F., and Lou, M. F., Does glutathione-S-transferase dethiolate lens protein-thiol mixed disulfides A comparative study with thioltransferase. Exp. Eye Res. 68, 715-724 (1999). 

There may also be conjunctivitis with vascularization of the cornea and opacity of the lens. This is the only lesion for which we know a possible biochemical basis - glutathione is important in maintaining the normal clarity of crystallin in the lens, and glutathione reductase is a flavoprotein that is particularly sensitive to riboflavin depletion. 

The lens grows with age, and colorations or opacities may develop and interfere with vision. Cataract formation may be enhanced by some miotics, steroids, and phenothi-azines. Aldose reductase inhibitors, which prevent the conversion of sugars to polyols, appear to prevent or delay diabetic cataract. Levels of glutathione and other compounds drop during the formation of some types of cataracts.The pharmacokinetics of delivery and penetration of such compounds into the crystalline lens is currently of great interest. 

Glu-Val S-(a, 3-Dicarboxyethyl)glutathione Calf lens Calam and Waley... 

Reddy, V.N. and Giblin, F.J. (1984). Metabolism and function of glutathione in the lens. Ciba Eound Symp 106, 65-87. 

Ferrer JV, Cased E, Sastre J, Pallardd V, Asensi M,Vina J (1990) Age-related changes in glutathione synthesis in the eye lens. Biochem J 269 531-534... 

Giblin, F.J. (2000) Glutathione a vital lens antioxidant,./. Ocul. Pharmacol. Ther., 16,121-135. Ham, W.T., Mueller, H.A., Ruffolo, J.J., Guerry, D., and Guerry, R.K. (1982) Action spectrum for retinal injury from near ultraviolet radiation in the aphakic monkey, Am. J. Ophthal., 93, 299-305. 

Singh SV, Srivastava SK, Awasthi YC. Purifrcation and characterization of the 2 forms of glutathione S-transferase present in human lens. Exp Eye Res 1985 41 201-207. 

Glutathione peroxidase has a molecular weight between 76,000 and 92,000 daltons and contains four identical 19-23,(X)0 dalton subunits , each of which contains a single selenocysteine residue . Purified forms of the enzyme have been obtained from the red blood cells of cattle , sheep and humans as well as from rat liver and bovine lens . An amino acid composition of homogeneous rat liver glutathione peroxidase has been determined and an X-ray diffi-action study at 2.8 A resolution has been published . There is some discrepancy between these two studies since the amino acid analysis indicates two cysteine residues per subunit which were not detected by the X-ray study. This point will have to be clarified. The X-ray study has shown that the active selenocysteines are found in flat depressions on the surface of the molecule which exists in long a-helices. 

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