Re-epithelialization of the rat cornea is accelerated by blockade of opioid receptors.
A native opioid peptide, [Met5]-enkephalin, termed opioid growth factor (OGF), serves as a constitutively expressed and autocrine produced inhibitory molecule related to developing, neoplastic, renewing, and healing tissues. The present study was designed to examine the effects of interfering with opioid-receptor interaction during re-epithelialization of the cornea in the rat using both systemic injections and topical applications of the potent opioid antagonist naltrexone (NTX). A 4 mm diameter epithelial defect was made in the center of the rat cornea. NTX injected twice daily or applied as eyedrops four times daily significantly accelerated re-epithelialization compared to controls. Beginning as early as 8 h after wounding, both the systemic and topical NTX treatment groups had defects that were approximately 10% to 67% smaller than control abrasions at the time points examined. Similarly, the rate of healing for the NTX groups was 4.7- and 2.8-fold greater than controls for systemic and topical paradigms, respectively. The incidence of complete re-epithelialization in animals given systemic administration of NTX was markedly accelerated in comparison to control rats; however, differences in incidence of repair between NTX and control groups receiving topical application were not observed. These results show that native opioid peptides function in wound healing, and exert a tonically inhibitory influence at the receptor level on repair of corneal epithelial injuries.
Departments of Neuroscience and Anatomy, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA. isz1@psu.edu
I S
IS
Zagon
J W
JW
Sassani
P J
PJ
McLaughlin
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000503:physiopathology*; D065306:Corneal Injuries; D004848:Epithelium / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000502:physiology*; D014950:Wounds, Penetrating / Q000503:physiopathology*
D009292:Narcotic Antagonists; D009271:Naltrexone