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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Published in:Investigative ophthalmology & visual science Vol. 50; no. 10; p. 4941
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 01.10.2009
Subjects:
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
Online Access:Get more information
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Summary: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.
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ISSN:1552-5783
1552-5783
DOI:10.1167/iovs.09-3602