Topically applied naltrexone restores corneal reepithelialization in diabetic rats.
OBJECTIVE
Complications of diabetes include an increased risk of delayed corneal epithelial wound healing. This study examined the efficacy of naltrexone (NTX), an opioid antagonist, by topical application in facilitating the repair of such lesions.


METHODS
NTX, in concentrations of 10(-4), 10(-5), or 10(-6) M, was administered topically 4 times per day for 7 days to the abraded eye of type 1 diabetic rats (DB), DB animals receiving insulin and normoglycemic (DB-IN), and nondiabetic (Normal) rats, beginning 8 weeks following the onset of diabetes.


RESULTS
In comparison to DB animals receiving sterile vehicle (SV), DB-NTX rats had 25%-83% smaller defects, a reduction of 24 h (approximately 33%) in closure time, and 20%-42% faster healing rates. DB rats receiving 10(-4) and 10(-5) M NTX were equal to, or surpassed, Normal animals in all parameters of wound closure. NTX also enhanced wound repair in DB-IN and Normal animals relative to their respective SV group. No adverse effects of NTX administration on a variety of noninvasive or invasive measures were discerned.


CONCLUSIONS
Topically applied NTX is not only feasible, but also effective over a one hundredfold dosage for accelerating corneal wound healing in diabetic subjects.
Klocek
Matthew S
MS
Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Sassani
Joseph W
JW
McLaughlin
Patricia J
PJ
Zagon
Ian S
IS
D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D003315:Cornea; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000209:etiology; D004247:DNA / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D019573:Epithelium, Corneal / Q000187:drug effects*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D014945:Wound Healing / Q000187:drug effects
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D009271:Naltrexone; D004247:DNA