Netrin-1 Overexpression in Oxygen-Induced Retinopathy Correlates with Breakdown of the Blood-Retina Barrier and Retinal Neovascularization

Purposes: Recent research has shown netrin-1 to promote neovascularization. We evaluate the expression of netrin-1 during retinal neovascularization in a murine model of oxygen-induced retinopathy. Methods: C57BL/6J mice were exposed to 75 +/- 5% oxygen for 5 days and returned to room air to induce retinal neovascularization. Retinal neovascularization was observed by fluorescence angiography and was quantified by counting the endothelial nuclei protruding into the vitreous cavity after hematoxylin-eosin staining. RTPCR and Western blot analyses were used to determine retinal netrin-1 mRNA and protein levels at postnatal days (PN) 13, 15 and 17. Results: In fluorescence angiograms, irregular neovascularization and fluorescein leakage were observed surrounding the unperfused areas in the hypoxic group. The hypoxic group had, on average, 50.70 +/- 4.56 neovascular nuclei protruding into the vitreous body, while similar nuclei were absent in the control group. Compared to the normoxic group, there were significant increases in both retinal netrin-1 mRNA and protein levels in the hypoxic group at PN13, PN15 and PN17. Conclusion: The netrin-1 level increases in murine retina under hypoxia and may be key in inducing retinal neovascularization. Copyright (C) 2011 S. Karger AG, Basel