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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)
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.
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.
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.
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.
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