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RA Barreiro, R Schadlu, H Kaplan, O Volpert, T Ferguson; Fas/Fas Ligand Regulation of Neovascularization in Ischemic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):778.
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Purpose:To define a role for Fas/FasL in oxygen-induced retinopathy and to explore the mechanism of PEDF (Pigment epithelium derived growth factor) inhibition in this model. Methods:Seven day-old mice C57BL/6J (B6) and FasL-defective (B6-gld) were exposed to 75% oxygen for 5 days (p7-p12) and returned to room air. On day p17 vascular architecture was assessed microscopically after perfusion with FITC-dextran and preretinal nuclei were quantified in PAS and hematoxylin staining. In some experiments, B6 and B6-gld mice were treated with i.p. varying doses of PEDF and vascular architecture and preretinal nuclei counts were compared with control animals. Results:: After oxygen treatment, retinal vessels had a higher degree of tortuousity centrally and peripherally in gld compared to B6. The number of microaneurysms in gld far outweighed the number of microaneurysms in B6. The number of preretinal nuclei and the amount of neovascular tufts were significantly increased in gld versus B6 wild-type mice. Treatment with PEDF (25 µ g/day) reduced by 40% the number of preretinal nuclei in both B6 and gld mice. Treatment with 10 µ g/day had no effect in either strain. Conclusion:Fas/FasL interactions regulate the extent of oxygen-induced retinal neovascularization. Since PEDF inhibited neovascularization in both B6 and gld mice, Fas/FasL interaction is probably not the mechanism for inhibition by this molecule
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