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MH Davies, AE Morganroth, RC Ilg, MR Powers; Fas-FasL Pathway Contributes to the Apoptotic Response in a Model of Oxygen-Induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):779.
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Purpose: We previously reported an increase in preretinal neovascularization in Fas ligand (FasL) deficient mice in a model of oxygen-induced retinopathy (IOVS, 41:S141). The present study was performed to further elucidate the role of the Fas-FasL pathway in regulation of retinal apoptosis. Methods: Postnatal day 7 (P7) FasL deficient (gld) mice and congenic C57BL/6 (B6) mice were exposed to 75% oxygen for up to 5 days (P12), and then recovered in room air. Apoptotic cells were localized in FITC-perfused whole mount retinas (n=6) from oxygen-exposed mice using a standard TUNEL technique on P17. Eyes from oxygen-exposed mice and unexposed controls were also obtained on days P7, P8, P10, P12, P14, P17, & P21 and processed for histopathological examination and RT-PCR analysis. TUNEL analysis was also performed on P17 retinal tissue sections to compare apoptosis in preretinal neovascular tufts from oxygen-exposed gld (n=6) and B6 mice (n=6). RT-PCR was used to examine retinal expression of Fas in oxygen-exposed and unexposed gld and B6 mice. Results: Retinal whole mounts demonstrated apoptotic cells in circumferential patterns along the transitional zone of vascular and avascular retina in both gld and B6 oxygen exposed mice. The outer periphery of the retinas also showed apoptotic cells in regions of avascularity in both gld and B6 mice. The TUNEL assays revealed an increased number of apoptotic cells (∼60%) located in the neovascular tufts of the B6 mice as compared to the gld mice, despite more preretinal neovascular nuclei in the gld mice. RT-PCR results demonstrated increased expression of Fas in oxygen-exposed gld and B6 mice on P14 and P17. Conclusion: Our results demonstrate that apoptosis plays a role in the retinal response to oxygen-induced injury. Additionally, the Fas-FasL pathway may play a previously unrecognized role in the regulation of retinal response to ischemic-induced injury. The increased neovascular tufts in the gld mice, in conjunction with reduced TUNEL positive cells, suggests that Fas-FasL mediated apoptosis may play a role in vascular tuft regression.
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