Use of topical insulin to normalize corneal epithelial healing in diabetes mellitus.
OBJECTIVE
To determine whether topical application of insulin normalizes delayed corneal wound healing in rats with diabetes mellitus (DB).


METHODS
Diabetes mellitus was induced with streptozocin. A 5-mm corneal abrasion at 9 or 11 weeks was treated topically for 7 days (4 times daily) with 1, 2, or 5 U of insulin or with sterile vehicle (SV).


RESULTS
Residual corneal epithelial defects of rats with DB receiving SV (hereafter called DB SV rats or animals) were approximately 35% larger than in healthy animals receiving SV (hereafter called healthy SV rats or animals). Rats with DB receiving topical insulin had wounds ranging from 19% to 60% smaller than DB SV rats, corresponding to wound sizes in healthy SV rats. Topical insulin had no effect on reepithelialization of corneal wounds in healthy SV rats. Insulin did not affect corneal thickness, ocular pressure, or serum glucose level. The corneal sensitivity of DB SV rats was markedly reduced from healthy SV rats, but rats with DB given insulin had corneal sensitivity values comparable to the healthy SV group. DNA synthesis was decreased in DB SV corneal epithelium but was comparable to that in healthy SV rats after they received insulin; apoptosis and necrosis levels were similar in all groups.


CONCLUSIONS
Topical insulin normalizes corneal reepithelialization in diabetic rats.


CONCLUSIONS
Direct application of insulin may serve as an important strategy for treating diabetic keratopathy.
Zagon
Ian S
IS
Department of Neural and Behavioral Sciences, Mail Code H109, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA 17033, USA. isz1@psu.edu
Klocek
Matthew S
MS
Sassani
Joseph W
JW
McLaughlin
Patricia J
PJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000293:injuries; D019793:Fluorescein / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005500:Follow-Up Studies; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014949:Wounds, Nonpenetrating / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D007328:Insulin; D009883:Ophthalmic Solutions; D004247:DNA; D019793:Fluorescein