%0 Journal Article
%A Chen, Ling
%A Sham, Caroline W.
%A Chan, Ann M.
%A Francisco, Loise M.
%A Wu, Yin
%A Mareninov, Sergey
%A Sharpe, Arlene H.
%A Freeman, Gordon J.
%A Yang, Xian-Jie
%A Braun, Jonathan
%A Gordon, Lynn K.
%T Role of the Immune Modulator Programmed Cell Death-1 during Development and Apoptosis of Mouse Retinal Ganglion Cells
%B Investigative Ophthalmology & Visual Science
%D 2009
%R 10.1167/iovs.09-3602
%J Investigative Ophthalmology & Visual Science
%V 50
%N 10
%P 4941-4948
%@ 1552-5783
%X   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. 
%[ 3/5/2021
%U https://doi.org/10.1167/iovs.09-3602