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Biomedical subjects

S D Varma

Publications and source records attributed to S D Varma.

At least 91 records · Page 5Linked to original sources

Ocular complications.

Ocular complications of diabetes in humans are reviewed briefly, and experimental models available for study of the complications are described. Potentially suitable models include not only diabetic animals, but also nondiabetic animals in which analogous lesions have been demonstrated. Many abnormalities of the lens, cornea, iris, and retina comparable to those of diabetes in humans may be observed in diabetic animals, although all abnormalities are not necessarily observed in every species. Retinal changes, in particular, may occur in diabetic animals of several species, but only in large animals (dogs, primates) have saccular capillary aneurysms been reproduced consistently, together with other retinal changes typical of diabetes in humans. A few examples of the uses of animal models are offered, and attention is called to a lack of animal models of proliferative diabetic retinopathy and of rubeosis iridis.

Animals↗

Superoxide radical scavenging agents in treatment of alkali burns. An experimental study.

To test the hypothesis that superoxide radicals are involved in tissue destruction after alkali burns, superoxide dismutase, ascorbic acid, and glutathione were used as superoxide radical scavenging agents. Daily subconjunctival injections were given in rabbit eyes after alkali burns. Both superoxide dismutase and ascorbic acid were effective in preventing corneal perforations. Glutathione did not show any beneficial effect. These experiments suggest that superoxide radical scavenging agents may be useful in the treatment of ocular alkali burns.

Alkalies↗

Siderosis from a retained intraocular stone.

A penetrating intraocular stone caused a retinal detachment that was repaired successfully. The patient returned 18 months later with siderosis bulbi. The patient was followed by serial neurosensory tests for the next three years. The electro-oculogram (EOG) showed the greatest abnormality, while the electroretinogram (ERG) and dark adaptation, although initially affected, showed no further deterioration. Surgical procedures on this eye included linear extraction of the siderotic lens, anterior vitrectomy, and irrigation of a hyphema. Fluorescein angiogram revealed a siderotic deposit on the retina. Progressive visual field loss prompted removal of the stone foreign body by an eye-wall resection technique. Five years later vision was 20/30. While dark adaptation, EOG, and ERG remained stable, the visual fields showed progressive constriction. Fluorescein angiogram revealed pigment epithelial defects, cystoid macular edema, reduced peripheral circulation, and progressive clearing of the retinal iron deposits.

Adult↗

Refractive change in alloxan diabetic rabbits. Control by flavonoids I.

The rabbit eye is hyperopic by approximately 4D. The induction of diabetes leads to a further enhancement in the degree of hyperopia. This enhancement is attenuated substantially by flavonoids as inhibitors of aldose reduction. The development of refractive changes in diabetic lens involves aldose reductase catalyzed polyol synthesis.

Aldehyde Reductase↗

Light-induced damage to ocular lens cation pump: prevention by vitamin C.

The cation pump activity of the ocular lens was damaged by exposure to light in the presence of riboflavin phosphate. The intensity of light was similar to that used for reading purposes. The observed light-induced damage was due to superoxide or its derivatives, the superoxide being produced photochemically. Such damage was attenuated by vitamin C in amounts comparable to that in the aqueous humor. Thus, a new role for the high ascorbate level present in the anterior chamber fluid and the lens has been suggested. Ascorbate in other tissues also might have this novel physiological function of protecting against damage due to superoxide and its derivatives produced during normal cellular oxidation.

Animals↗

Implications of aldose reductase in cataracts in human diabetes.

Cataracts removed intracapsularly by cryoprobe technique from human diabetics were analyzed for sugars and polyols by gas liquid chromatography. The contents of sorbitol and fructose of lenses followed blood glucose levels at least up to 250 mg/dl. Studies indicate that human lens is capable of synthesizing substantial amounts of polyol pathway metabolites given exposure to high glucose levels such as are prevalent in diabetes. The synthesis of sorbitol was found to be susceptible to quercitrin, an inhibitor of aldose reductase. The implications of these findings in the formation of cataracts in diabetic individuals have been discussed.

Aldehyde Reductase↗

Diabetic cataracts and flavonoids.

Oral administration of quercitrin, an inhibitor of aldose reductase, leads to a significant decrease in the accumulation of sorbitol in the lens of diabetic Octodon degus. The onset of cataract is effectively delayed when quercitrin is continuously administered. Thus in these diabetic animals, as in galactosemic rats, the use of an effective aldose reductase inhibitor impedes the course of cataract development. These observations support the hypothesis that in diabetes, as in galactosemia, aldose reductase plays a key role in initiating the formation of lens opacity.

Alcohol Oxidoreductases↗

Aldose reductase in retinal mural cells.

Cultured mural cells (intramural pericytes) from adult rhesus retinal capillaries were examined for the presence of the sorbitol pathway. A radioimmunoassay for human aldose reductase, cross-reactive with rhesus lens aldose reductase, showed the presence of this enzyme in our cultured cells. Mural cells grown in culture media containing normal (10 mM) and high (40 mM) levels of glucose were examined for polyol accumulation by gas-liquid chromatography. Cells incubated in high glucose medium showed a threefold increase in sorbitol concentration over cells grown at low glucose levels. After 30 days in high glucose medium, mural cells formed dense multilayered areas with extensive cellular debris. These findings suggest the presence of the sorbitol pathway in cultured retinal mural cells and cellular degeneration in high glucose medium; this may have possible implications in the pathogenesis of diabetic retinopathy.

Alcohol Oxidoreductases↗

Flavonoids as inhibitors of lens aldose reductase.

Flavonoids are effective inhibitors of lens aldose reductase. Quercetin, quercitrin, and myricitrin are significantly more potent than the previously known aldose reductase inhibitors. The inhibitory activity is of the noncompetitive type. In addition, quercitrin effectively blocks polyol accumulation in intact rat lenses incubated in medium containing high concentration of sugars.

Alcohol Oxidoreductases↗

Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor.

An orally active inhibitor of aldose reductase, 1,3-dioxo-1H-benz[de]-isoquinoline-2(3H)acetic acid (AY-22,284), prevented cataractous changes in cultured lenses exposed to high concentrations of galactose. When given orally, AY-22,284 markedly decreased the accumulation of polyols in the lenses and sciatic nerves of galactosemic rats and rats with streptozotocin-induced diabetes. In addition, treatment of galactosemic rats with AY-22,284 effectively suppressed the formation of cataracts.

Acetates↗