Effects of topical aldose reductase inhibitor CT-112 on corneal sensitivity of diabetic rats.
OBJECTIVE
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 (ARI), 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 ARI. 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 ARI 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 ARI 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.
Hosotani
H
H
Department of Ophthalmology, Osaka University Medical School, Japan.
Ohashi
Y
Y
Kinoshita
S
S
Matsumoto
T
T
Awata
T
T
D000287:Administration, Topical; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001767:Blinking / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006987:Hypesthesia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000008:administration & dosage*; D045162:Thiazolidinediones; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure
D004791:Enzyme Inhibitors; D009883:Ophthalmic Solutions; D013844:Thiazoles; D045162:Thiazolidinediones; C051003:risarestat; D000449:Aldehyde Reductase