April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Programmed Cell Death-1 Ligands 1 and 2 Actively Promote Neuronal Cell Death in the Developing Mouse Retina
Author Affiliations & Notes
  • C. W. Sham
    Pathology & Laboratory Medicine,
    University of California Los Angeles, Los Angeles, California
  • A. M. Chan
    Ophthalmology, Jules Stein Eye Institute,
    University of California Los Angeles, Los Angeles, California
  • L. M. Francisco
    Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • A. H. Sharpe
    Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
  • G. J. Freeman
    Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
    Medicine, Harvard Medical School, Boston, Massachusetts
  • X.-J. Yang
    Ophthalmology, Jules Stein Eye Institute,
    University of California Los Angeles, Los Angeles, California
  • J. Braun
    Pathology & Laboratory Medicine,
    University of California Los Angeles, Los Angeles, California
  • L. K. Gordon
    Ophthalmology, Jules Stein Eye Institute,
    University of California Los Angeles, Los Angeles, California
    Ophthalmology Section, Surgery and Perioperative Care, Greater Los Angeles VA Healthcare System, Los Angeles, California
  • Footnotes
    Commercial Relationships  C.W. Sham, None; A.M. Chan, None; L.M. Francisco, None; A.H. Sharpe, None; G.J. Freeman, None; X.-J. Yang, None; J. Braun, None; L.K. Gordon, None.
  • Footnotes
    Support  NIH T32 GM08042 (UCLA Medical Scientist Training Program to CWS), NIH/NIAID R01 AI021256 (UCLA Immunopathology Training Grant to CWS)
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 143. doi:
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    • Get Citation

      C. W. Sham, A. M. Chan, L. M. Francisco, A. H. Sharpe, G. J. Freeman, X.-J. Yang, J. Braun, L. K. Gordon; Programmed Cell Death-1 Ligands 1 and 2 Actively Promote Neuronal Cell Death in the Developing Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):143.

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

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Abstract

Purpose: : Development of functional neuronal networks involves both positive and negative synapse selection: neurons making ‘correct’ connections will survive, while those making ‘incorrect’ connections will be eliminated by programmed cell death (PCD). Retinal maturation is an example of ontogenic neuronal culling, providing a model to study PCD in the central nervous system. We have previously shown that the immunoregulatory receptor programmed cell death-1 (PD-1) acts to actively promote retinal ganglion cell (RGC) death during murine postnatal retina maturation. In this study, we aim to identify the neuronal PD-1 ligands, regulating PD-1-mediated PCD and to confirm their functional role in developmental RGC death in vivo.

Methods: : PD-L1/L2 double knockout (DKO) mice in the C57BL/6 background or wild type controls were studied. PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2) gene expression were measured at postnatal days P0, 2, 4, 7, 30 by quantitative real-time PCR. Quantification of RGCs was performed after immunofluorescence staining for NeuN and Brn3a at various postnatal ages.

Results: : The two known immune PD-1 ligands, PD-L1 and PD-L2, are dynamically transcribed during retina development, with gene expression peaking during the first week of postnatal life and settling to a basal level in the mature retina. In the PD-L1/L2 DKO retina, there is a significant numerical increase in RGCs (35% in P2, 30% in adult), as compared to wild type.

Conclusions: : This work identifies PD-L1 and PD-L2 expression in neural retina and concordant with our prior studies, supports a role for the PD-1/PD-ligand interaction in developmental RGC culling. These data collectively support a novel role for active promotion of neuronal cell death through a receptor-ligand engagement.

Keywords: ganglion cells • apoptosis/cell death • development 
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