Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells

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 wit...

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Vydané v:	Investigative ophthalmology & visual science Ročník 50; číslo 10; s. 4941
Hlavní autori:	Chen, Ling, Sham, Caroline W, Chan, Ann M, Francisco, Loise M, Wu, Yin, Mareninov, Sergey, Sharpe, Arlene H, Freeman, Gordon J, Yang, Xian-Jie, Braun, Jonathan, Gordon, Lynn K
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 01.10.2009
Predmet:	Animals Animals, Newborn Antigens, Surface - physiology Apoptosis Apoptosis Regulatory Proteins - physiology B7-1 Antigen - metabolism B7-H1 Antigen Blotting, Western Cell Count Cell Survival Fluorescent Antibody Technique, Indirect Gene Expression Regulation, Developmental - physiology Ligands Lymphocyte Activation Membrane Glycoproteins - metabolism Mice Mice, Inbred C57BL Mice, Knockout Peptides - metabolism Programmed Cell Death 1 Ligand 2 Protein Programmed Cell Death 1 Receptor Retina - growth & development Retina - metabolism Retinal Ganglion Cells - metabolism Retinal Ganglion Cells - pathology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Signal Transduction - physiology
ISSN:	1552-5783, 1552-5783
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Shrnutí:	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. 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. 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. These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1552-5783 1552-5783
DOI:	10.1167/iovs.09-3602