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Ling Chen, Caroline W. Sham, Ann M. Chan, Loise M. Francisco, Yin Wu, Sergey Mareninov, Arlene H. Sharpe, Gordon J. Freeman, Xian-Jie Yang, Jonathan Braun, Lynn K. Gordon; Role of the Immune Modulator Programmed Cell Death-1 during Development and Apoptosis of Mouse Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(10):4941-4948. doi: 10.1167/iovs.09-3602.
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purpose. Mammalian programmed cell death (PD)-1 is a membrane-associated receptor regulating the balance between T-cell activation, tolerance, and immunopathology; however, its role in neurons has not yet been defined. The hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina was investigated.
methods. Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western blot analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retinal explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR.
results. PD-1 is expressed in most adult RGCs and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases the survival of RGCs. Furthermore, PD-1–deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, gene expression of the immune PD-1 ligand genes Pdcd1lg1 and Pdcd1lg2 was found throughout postnatal retina maturation.
conclusions. These findings collectively support a novel role for a PD-1–mediated signaling pathway in developmental PCD during postnatal RGC maturation.
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