Response of the lens to oxidative-osmotic stress.
Both aldose reductase and glutathione reductase share a common cofactor, NADPH. Glutathione reductase is preferentially activated due to its higher affinity for the cofactor. Since NADPH is primarily consumed by glutathione reductase, which in conjunction with glutathione peroxidase detoxifies H2O2 present in the aqueous humor, the cataractogenic role of sorbitol-induced osmotic pressure must therefore depend on the availability of NADPH for aldose reductase activity. We examined the response of the lens to an oxidative-osmotic double stress and found that the lens indeed produced 79% less sorbitol and 45% less fructose than a lens subjected to the osmotic stress alone. Morphological studies showed that photo-oxidation damaged the epithelium where the cation pump resided. However, with additional osmotic stress, the swelling of lens fibers in the posterior pole region became more pronounced, and cell nuclei deep in the lens nuclear bow were dislodged to the posterior pole. This could be explained by the slight but significant loss of K+ in the lenses under the double stress. Apparently, the slightly decreased 86Rb uptake (26% loss), caused by photooxidation could not maintain adequate ionic balance even though the stress from accumulation of sorbitol + fructose was sub-maximal. No disturbance in the glycolytic activity or to the 86Rb efflux was found in these lenses, however.
D000818:Animals; D005947:Glucose / Q000494:pharmacology; D006600:Hexosephosphates / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism* / Q000648:ultrastructure; D008027:Light; D008297:Male; D008854:Microscopy, Electron; D009997:Osmotic Pressure; D010084:Oxidation-Reduction; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000096:biosynthesis
D006600:Hexosephosphates; D007773:Lactates; D013012:Sorbitol; D006861:Hydrogen Peroxide; D005947:Glucose; D011188:Potassium