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Abstract
Rabbit lenses were incubated in low- and high-glucose media in an attempt to evaluate the role of the sorbitol pathway in the production of this sugar cataract. The aldose reductase inhibitor, 3,3-tetramethylene glutaric acid (TMG), was employed to block sorbitol formation. Exposing lenses to high glucose leads to an initial linear increase in sorbitol content and lens water. During the first four days of incubation, lens swelling occurs in response to intracellular sorbitol accumulation. Swelling renders cell membranes more permeable to sodium and potassium. During the first four days in high glucose, the swollen lens is able to compensate for this increased leakiness to sodium and potassium, presumably through increasing cation pump activity. Thus there is no increase in the absolute cation level. However, on or about the fifth day in high glucose, the capacity of this compensatory mechanism is exceeded and abrupt changes in lens cations occur. Lens sodium rises and lens potassium falls; the net result is an increase in total cations. At a somewhat later stage, the inulin space of the lens increases as lens fibers rupture and/or become more permeable to inulin. The addition of TMG to the high-glucose medium practically abolishes sorbitol accumulation; it depresses lens swelling, preserves normal cation balance, and maintains lens clarity and transparency for eight days. This suggests that all of the aforementioned changes are interrelated and also emphasizes the primary role played by aldose reductase in the initiation of the entire sequence of cataractous change.