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Michael DeNiro, Falah H. Al-Mohanna, Futwan A. Al-Mohanna; Reversal of Reactive Gliosis Promote De Novo Vascular Remodeling and Prevent Retinal Vasculopathies. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4850.
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Retinal neovascularization [NV] is a major cause of blindness in ischemic retinopathies. Previous investigations have indicated that ischemia upregulates GFAP, PDGF-B, and iNOS expression. GFAP overexpression is a hallmark of reactive gliosis [RG], which is a major pathophysiological feature of retinal damage. In addition, PDGF -B has been implicated in proliferative retinopathies; while data have indicated that iNOS upregulation plays a pathological role by which it inhibits angiogenesis in the ischemic retina. It was the aim of this study to evaluate the efficacy of YC-1, a HIF-1 inhibitor, in modulating PDGF-B and iNOS expression and reversing RG and NV.
An array of assays to evaluate the effects of YC-1 on RG and NV; in vitro and in vivo.
Dual-intravitreal injections of YC-1;  reduced the hypoxia/ischemia-induced expression of GFAP, PDGF-B, and iNOS message and protein levels, in vivo and in vitro, respectively;  reduced the filopodial length and number in endothelial tip cells;  inhibited ischemic pathologic neovascular response;  promoted retinal microvascular repair and intra-retinal revascularization.
We demonstrate that YC-1 reversed RG and rescued the neurosensory retina during ischemic retinopathy through impairing the expression of GFAP in Müller cells. This is the first investigation that delves into the reversal of RG and the rescue of the neurosensory retina during ischemic retinal vasculopathies. This study reveals that YC-1 may exert pleiotropic promising therapeutic effects in the treatment of retinal and neuronal pathologies.
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