Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat
Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat Ian S. Zagon 1 , Joe B. Jenkins 2 , Joseph W. Sassani 3 , James D. Wylie 1 , Torre B. Ruth 1 , Jamie L. Fry 1 , C. Max Lang 2 and Patricia J. McLaughlin 1 1 Department of Neuroscience and Anatomy, The Pen...
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| Published in: | Diabetes (New York, N.Y.) Vol. 51; no. 10; pp. 3055 - 3062 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Alexandria, VA
American Diabetes Association
01-10-2002
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Naltrexone, an Opioid Antagonist, Facilitates Reepithelialization of the Cornea in Diabetic Rat
Ian S. Zagon 1 ,
Joe B. Jenkins 2 ,
Joseph W. Sassani 3 ,
James D. Wylie 1 ,
Torre B. Ruth 1 ,
Jamie L. Fry 1 ,
C. Max Lang 2 and
Patricia J. McLaughlin 1
1 Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
2 Department of Comparative Medicine, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
3 Department of Ophthalmology and Pathology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania
Abstract
Ulcers and erosions of the corneal epithelium, as well as delays in resurfacing of the cornea after wounding, are major causes
of ocular morbidity and visual loss in diabetes. To study whether intervention by the opioid antagonist naltrexone (NTX; 30
mg/kg, twice daily) can restore reepithelialization in diabetic cornea, we induced diabetes in rats by intravenous injection
of 65 mg/kg streptozotocin. After confirmation of diabetes, 5-mm-diameter epithelial defects that did not include the limbus
were created by mechanical scraping of the cornea. At 4 and 8 weeks, corneal reepithelialization was markedly subnormal, with
delays ranging from 11% to 17-fold in the diabetic animals compared with control counterparts. Rats that were diabetic for
8 weeks also had a significant decrease in the incidence of complete wound closure. At 4 and 8 weeks, diabetic animals that
were receiving NTX had an acceleration in reepithelialization compared with diabetic animals that were receiving vehicle and
even surpassed controls. DNA synthesis in the corneal epithelium of diabetic rats was decreased up to 90% of control levels,
and NTX exposure of diabetic subjects elevated the labeling index by up to eightfold from diabetic animals that were receiving
vehicle. Opioid growth factor and opioid growth factor receptor distribution were comparable in diabetic and control animals.
These results indicate a delay in reepithelialization that is dependent on the duration of diabetes and that intervention
of endogenous opioid-receptor interfacing with an opioid antagonist can facilitate the process of wound healing.
Footnotes
Address correspondence and reprint requests to Dr. Ian S. Zagon, Department of Neuroscience and Anatomy, H109, The Milton
S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033. E-mail: isz1{at}psu.edu .
Received for publication 23 April 2002 and accepted in revised form 26 June 2002.
ANOVA, analysis of variance; CCD, charged-coupled device; LI, labeling index; NTX, naltrexone; OGF, opioid growth factor;
OGFr, opioid growth factor receptor; STZ, streptozotocin.
DIABETES |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0012-1797 1939-327X |
| DOI: | 10.2337/diabetes.51.10.3055 |