Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Opioid Growth Regulatory System consists of opioid growth factor (OGF), [Met5]-enkephalin, and its unique receptor (OGFr). OGF inhibits cell division when bound to OGFr. Conversely, blockade of the interaction of OGF and OGFr, using the potent, long-acting opioid receptor antagonist, naltrexone (NTX), results in increased DNA synthesis and cell division. The authors have demonstrated both in vitro and in vivo that the addition of exogenous OGF or an increase in available OGFr decreases corneal epithelial cell division and wound healing. Conversely, blockade of the OGF-OGFr interaction by NTX or a decrease in the production of the OGFr increases corneal epithelial cell division and facilitates corneal epithelial wound healing. The authors also have demonstrated that depressed corneal and cutaneous wound healing, dry eye, and abnormal corneal sensitivity in type 1 and type 2 diabetes in animals can be reversed by OGF-OGFr blockade by NTX. Thus, the function of the Opioid Growth Regulatory System appears to be disordered in diabetic animals, and its function can be restored with NTX treatment. These studies suggest a fundamental role for the Opioid Growth Regulatory System in the pathobiology of diabetic complications and a need for studies to elucidate this role further.
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PMID:The Yin and Yang of the Opioid Growth Regulatory System: Focus on Diabetes-The Lorenz E. Zimmerman Tribute Lecture. 2770 86

The opioid growth factor (OGF)-OGF receptor (OGFr) pathway is present in the ocular surface and functions to maintain homeostasis of the epithelium. The OGF-OGFr pathway has been reported to be dysregulated in diabetic individuals and animal models, and is reflected in elevations of the inhibitory growth factor, OGF, chemically termed [Met5]-enkephalin. Recently, our laboratory reported elevated levels of OGF and OGFr in the serum and corneal epithelium of type 1 diabetic rats, suggesting that dysregulation of the OGF-OGFr axis may lead to dry eye, abnormal corneal surface sensitivity, and delayed re-epithelialization. Blockade of OGF-OGFr pathway using naltrexone, a potent opioid receptor antagonist, reverses dry eye symptoms and restores corneal surface sensitivity in diabetic rats when used as a therapy. Based on the evidence that both OGF and OGFr are elevated in type 1 diabetic rats, this study examined whether systemic or topical naltrexone treatment initiated at the time of induction of hyperglycemia could protect against the development of diabetic ocular surface complications. Diabetic male Sprague-Dawley rats treated systemically or topically with naltrexone had a delayed onset of dry eye and altered corneal surface sensitivity, and an improved healing rate for corneal wounds, that were comparable to non-diabetic rats. Serum levels of OGF were normal for rats receiving systemic naltrexone, and OGF tissue levels were normal for type 1 diabetic rats receiving twice daily naltrexone drops. OGFr levels remained elevated. These data support the role of the OGF-OGFr axis in regulation of ocular surface complications, and suggest that naltrexone therapy may be beneficial for pre-diabetic and early diabetic individuals.
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PMID:Blockade of OGFr delays the onset and reduces the severity of diabetic ocular surface complications. 3320 24