Diabetic cataract formation

Complications in diabetes (cataract formation and nephropathy in particular). 

Y. Morimitsu, K. Kubota, T. Tashiro, E. Hashizume, T. Kamiya, and T. Osawa, Inhibitory effect of anthocyanins and colored rice on diabetic cataract formation in the rat lens, in G, 2002, 503-508. 

Stevens, V. J., Rouzer, C. A., Monnier, V. M., and Cerami, A., Diabetic cataract formation Potential role of glycosylation of lens crystallins. Proc. Natl. Acad. Sci U.SA. 75,2918-2922 (1978). 

Chronic Complications - A great deal of interest has been generated in recent years, regarding the possibility that polyol accumulation may be fundamental to the development of diabetic complications in certain tissues. While sorbitol accumulation in the lens has long been implicated as being causally related to diabetic cataract formation , more recent work has provided compelling evidence that a similar situation may exist for the development of diabetic neuropathy " and macroangio-pathy. ... 

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. ... 

Late diabetic tissue injury (impairment of glomeruli, cataract formation) Protein glycooxidation Decrease in vitamin C and GSH concentrations... 

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. 

Hutton JC, Scholfield PJ, Williams JF, et al. The effect of an unsaturated fat diet on cataract formation in streptozotocin-induced diabetic rat. Br J Nutr 1976 36 161-177. 

Glycosylation of the lens crystallin proteins (All, C8, C9, H6a, M5, M31, P4, S45) is of considerable interest because of the long-lived nature of the a, P, and 7 crystallins, the molecular aggregation and decreased solubility of the glycosylated products, the possibility of further reactions leading to browning effects (M28, M29), and their relevance to cataract formation and other complications in diabetes and aging. 

Orally administered steroids should only be administered for short periods of time since long-term therapy may lead to a variety of side effects, including suppression of adrenal function, hypertension, aggravation of diabetes, exaeerbation of infections, osteoporosis, cataract formation, and peptic ulcer formation. The availability of aerosol formulations of beclomethasone has fticilitated the long-term use of this type of therapeutic since this route of administration deposits the drug directly in the airways, where it can act therapeutically but is not absorbed into the systemic circulation. 

Fructose synthesis from glucose in the polyol pathway occurs in seminal vesicles and other tissues. Aldose reductase converts glucose to the sugar alcohol sorbitol (a polyol), which is then oxidized to fructose. In the lens of the eye, elevated levels of sorbitol in diabetes mellitus may contribute to cataract formation. 

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