Effects of topical aldose reductase inhibitor CT-112 on corneal sensitivity of diabetic rats

Purpose. To investigate whether the loss in corneal sensation observed in human diabetics could be duplicated in diabetic rats and if this abnormality could be prevented by topical instillation of an aldose reductase inhibitor (ART), CT-112. Methods. Rats were made diabetic by injection of streptozotocin. Some of these rats were treated with eye drops of CT-112 while others were treated with the same vehicle solution without ART. Normal rats served as controls. Corneal sensitivity was measured by means of a Cochet-Bonnet aesthesiometer, using the blink reflex as an objective sign. Corneal changes in ultrastructure in diabetic rats were also observed. Results. The corneal sensitivity of diabetic rats was significantly decreased and this change was prevented by ARI treatment. Ultrastructurally, degenerations of axons and mitochondria of the corneal nerve were seen in the diabetic rats and the ART treatment prevented these morphological changes. Conclusions. It is clear that corneal hypesthesia occurs in diabetic rats as it does in human diabetics, and treatment with an ART prevents this change. Along with the functional abnormality, the ultrastructural changes of corneal nerve also occur in diabetic rats, and they are prevented by ARI. These results strongly suggest that aldose reductase is involved in corneal hypesthesia and ultrastructural changes of corneal nerve in diabetic rats. These defects are ameliorated by aldose reductase inhibitor.