March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Neuronal Programmed Cell Death-1 Ligand Expression Regulates Retinal Ganglion Cell Number in Neonatal and Adult Mice
Author Affiliations & Notes
  • Caroline W. Sham
    Ophthalmology,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
    Pathology, David Geffen School of Medicine, UCLA, Los Angeles, California
  • Ann M. Chan
    Ophthalmology,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • Jacky Man Kwong Kwong
    Ophthalmology,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • Joseph Caprioli
    Ophthalmology,
    Glaucoma,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • Steven Nusinowitz
    Ophthalmology,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
  • Ling Chen
    Ophthalmology, Eye and ENT Hospital, Shanghai Medical School, Shanghai, China
  • Jonathan Braun
    Pathology, David Geffen School of Medicine, UCLA, Los Angeles, California
  • Lynn K. Gordon
    Ophthalmology,
    Jules Stein Eye Institute, UCLA, Los Angeles, California
    Ophthalmology Section, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California
  • Footnotes
    Commercial Relationships  Caroline W. Sham, None; Ann M. Chan, None; Jacky Man Kwong Kwong, None; Joseph Caprioli, None; Steven Nusinowitz, None; Ling Chen, None; Jonathan Braun, None; Lynn K. Gordon, None
  • Footnotes
    Support  NIH T32 GM08042; NIH/NIAID R01 AI021256; NIH/NEI T32 EY007026
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3954. doi:
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      Caroline W. Sham, Ann M. Chan, Jacky Man Kwong Kwong, Joseph Caprioli, Steven Nusinowitz, Ling Chen, Jonathan Braun, Lynn K. Gordon; Neuronal Programmed Cell Death-1 Ligand Expression Regulates Retinal Ganglion Cell Number in Neonatal and Adult Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3954.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : During mouse retina maturation the final number of retinal ganglion cells (RGCs) is determined by highly regulated programmed cell death. Previous studies demonstrated that the immunoregulatory receptor programmed cell death-1 (PD-1) promotes developmental RGC death. To identify the functional signaling partner(s) for PD-1, we identified retinal expression of PD-1 ligands and examined the effect of PD-1 ligand expression on RGC number. We also explored the hypothesis that PD-1 signaling promotes development of functional visual circuitry.

Methods: : Characterization of retinal and brain PD-L1 expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands to RGC number was examined in PD-ligand knockout mice. Retinal architecture was assessed by spectral domain optical coherence tomography and retinal function was analyzed by electroretinography in WT and PD-L1/L2 double deficient mice.

Results: : PD-L1 expression is found throughout the neonatal retina and persists in adult RGCs, bipolar interneurons, and Müller glia. In the absence of both PD-ligands, there is a significant numerical increase in RGCs (34% at P2, 18% in adult), as compared to wild type, and PD-ligands have redundant function in this process. Despite the increased RGC number, adult PD-L1/L2 double knockout mice have normal retinal architecture and outer retina function.

Conclusions: : This work demonstrates that PD-L1 and PD-L2 together impact the final number of RGCs in adult mice and supports a novel role for active promotion of neuronal cell death through PD-1 receptor-ligand engagement.

Keywords: retinal development • ganglion cells • retina: proximal (bipolar, amacrine, and ganglion cells) 
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