Studies on Cataractogenesis in Humans and in Rats with Alloxan-Induced Diabetes

Abstract

The effect of cataractogenesis on the behavior of some enzymes involved in glucose metabolism was examined histochemically both in human lenses and in rat lenses from rats with alloxan-induced diabetes. Several modifications in the currently available techniques were made in order to localize glucose-6-phosphate dehydrogenase, aldose reductase, sorbitol dehydrogenase, hexokinase and ketohexokinase in ocular lens. Human cataractous lenses showed a precipitous drop in glucose-6-phosphate dehydrogenase activity, whereas the lenticular tissues of alloxan-treated rats showed a gradual decrease of this enzyme with the prolongation of diabetes. Aldose reductase activity increased in hypermature and senile diabetic cataracts, whereas sorbitol dehydrogenase activity decreased in these lenses. Similarly, in alloxan-diabetic rat lenses the activity of aldose reductase increased while that of sorbitol dehydrogenase decreased with the prolongation of diabetes. Attempts were made to localize hexokinase and ketohexokinase in ocular lens.

Sodium Pump Inhibition and Regional Expression of Sodium Pump α-Isoforms in Lens

“…Our results are generally consistent with those of others, 3,4,8 which have considered the location of Na ϩ ,K ϩ -ATPase activity (but not isoforms) in human and rat lens. In human lens, ATPase reaction products were found exclusively in the epithelium.…”

“…[1][2][3][4][5][6][7][8] The mechanisms for this reduction in Na ϩ ,K ϩ -ATPase activity are not completely understood but could result from an endogenous inhibitor or reductions in functional sodium pump units. We have recently isolated a labile, endogenous Na ϩ ,K ϩ -ATPase inhibitor from the peritoneal dialysate of hypertensive renal failure patients.…”

“…In human lens, ATPase reaction products were found exclusively in the epithelium. 3,8 Kobatashi et al 6 measured the activity of Na ϩ ,K ϩ -ATPase in the 3 regions of normal human lens and found a third of the total activity in the epithelial monolayer, half in the cortical fibers, and the remainder in the nucleus. Our findings are also similar to those of more recent studies that have begun to explore sodium pump isoforms in lens.…”

“…2 Rodriguez-Sargent et al 2 recently reported that development of cataracts in Dahl S rats in response to a high salt diet can be predicted by a reduction in ouabain-sensitive Na ϩ ,K ϩ -ATPase activity several weeks before cataract formation. Likewise, a reduction in lens Na ϩ ,K ϩ -ATPase (sodium pump) activity occurs in several other animal models of cataract [2][3][4][5] and in human cataract formation. 3,6 -8 A similar reduction in sodium pump activity is also a common feature of hypertension and is thought to be mediated in part by a circulating sodium pump inhibitor 9 called either digitalis-like factor (DLF) or ouabain-like factor.…”

Lenticular Calcium, Magnesium, and Iron Levels in Diabetic Rats and Verapamil Effect

“…This is sufficient to account for an osmotic swelling within the lens [3]. However, it has also been stated that a breakdown in phosphoinositide metabolism destroys the structure of the lens, which in turn leads to cataract formation [4]. Recent research efforts have focused on lens electrolyte imbalances in diabetic cataract [5].…”