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.
Zagon
I S
IS
Departments of Neuroscience and Anatomy, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA. isz1@psu.edu
Sassani
J W
JW
McLaughlin
P J
PJ
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