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M. S. Klocek, J. W. Sassani, P. J. McLaughlin, A. M. Komaromy, I. S. Zagon; Corneal Vascularization and Granulation Tissue Formation Accompanying Delayed Corneal Epithelial Wound Healing in Diabetic Rats is Prevented by Topical Treatment With Naltrexone. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1694.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal neovascularization (CNV) accompanies many corneal disorders, particularly inflammation and ulceration. However, granulation tissue formation is uncommon. Moreover, corneal epithelial healing defects frequently are complications of the diabetic state (diabetic keratopathy). Topical naltrexone (NTX) therapy facilitates corneal epithelial wound healing in a standardized model of corneal abrasions in diabetic rats. Recently, we have noticed an unusual form of keratopathy accompanied by vascularization and granulation tissue formation associated with delayed epithelial wound healing in diabetic rats. The purpose of the present study was to determine if this keratopathy could be prevented with topical NTX therapy.
Type-1 diabetes (glucose levels >400 mg/dl) was induced with streptozotocin. Eight weeks after induction of diabetes, a 5 mm central corneal wound was created in the right eye of each rat. Eye drops (0.05 ml) of 10-4 or 10-5 M NTX, or sterile vehicle (SV), were given topically for 4 times daily over a 7 day period. Normal (non-diabetic) rats received SV. CNV was monitored with a hand held Zeiss Slit-Lamp (Zeiss HSO 10 Hand Slit Lamp, Dublin, CA) every other day for a 3-week period after initial wounding. Trichrome histological staining was performed to determine the presence and extent of CNV, and hematoxylin and eosin staining was utilized for investigation of inflammatory cells.
CNV did not occur in normal SV rats (n=26), or DB rats receiving 10-4 M or 10-5 M NTX (n=18/treatment). CNV was present in 41% of DB SV rats (n=29). The incidence of CNV in DB SV animals was significantly different from the Normal SV group, as well as from DB rats receiving 10-4 M or 10-5 M NTX (p<0.001). Granulation tissue was not present in the corneas of the animals with CNV until 4 days after onset of the CNV.
These data indicate that topically applied NTX prevents neovascularization and granulation tissue formation in our standard model of diabetic corneal abrasion.
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