Prevention of exuberant granulation tissue and neovascularization in the rat cornea by naltrexone.
OBJECTIVE
To determine whether topical application of naltrexone prevents exuberant granulation tissue formation with neovascularization in diabetic rat corneas.


METHODS
Diabetes was induced with streptozotocin. A 5-mm corneal abrasion at 9 or 11 weeks was treated topically for 7 days (4 times daily) with naltrexone or a sterile vehicle.


RESULTS
Within 2 to 5 days after reepithelialization, diabetic rats given the sterile vehicle had a 41% incidence of corneal lesions represented by exuberant granulation tissue with corneal neovascularization extending from the limbus. These lesions exhibited edema, cellular and vascular inflammation, and disruption of stromal lamella by fibrovascular tissue and calcium mineralization, but infection was not detected. No corneal lesions were recorded in the diabetic group treated with naltrexone or the control group given the sterile vehicle. Diabetic rats with corneal lesions given the sterile vehicle reepithelialized more slowly than diabetic rats given the sterile vehicle without such lesions, but no difference in blood glucose levels were noted.


CONCLUSIONS
Using a minimally invasive model in diabetic rats, topical naltrexone normalizes corneal wound healing and prevents neovascularization.


CONCLUSIONS
Direct application of naltrexone may serve as an important strategy for facilitating corneal healing and inhibiting corneal neovascularization.
Zagon
Ian S
IS
Department of Neural and Behavioral Sciences, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, USA. isz1@psu.edu
Klocek
Matthew S
MS
Griffith
James W
JW
Sassani
Joseph W
JW
Komáromy
András M
AM
McLaughlin
Patricia J
PJ
D000287:Administration, Topical; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016510:Corneal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003646:Debridement; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D019573:Epithelium, Corneal / Q000502:physiology; D015590:Fluorophotometry; D006097:Granulation Tissue / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage*; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects
D001786:Blood Glucose; D009292:Narcotic Antagonists; D009883:Ophthalmic Solutions; D009271:Naltrexone