@article {542156,
	title = {Neuronal programmed cell death-1 ligand expression regulates retinal ganglion cell number in neonatal and adult mice.},
	journal = {J Neuroophthalmol},
	volume = {32},
	number = {3},
	year = {2012},
	month = {2012 Sep},
	pages = {227-37},
	abstract = {OBJECTIVES: 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 the development of functional visual circuitry.

METHODS: Characterization of retinal and brain programmed cell death-1 ligand 1 (PD-L1) expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands, PD-L1, and programmed cell death-1 ligand 2 (PD-L2) to RGC number was examined in PD-ligand knockout mice lacking 1 or both ligands. Retinal architecture was assessed by spectral-domain optical coherence tomography, and retinal function was analyzed by electroretinography in wild-type 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 M{\"u}ller glia. In the absence of both PD-ligands, there is a significant numerical increase in RGCs (34\% at postnatal day 2 [P2] and 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.

CONCLUSION: This study 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 = {Aging, Animals, Antigens, CD274, Axons, Electroretinography, Mice, Mice, Inbred C57BL, Mice, Knockout, Optic Nerve, Programmed Cell Death 1 Ligand 2 Protein, Programmed Cell Death 1 Receptor, Retina, Retinal Ganglion Cells, Spectrum Analysis},
	issn = {1536-5166},
	doi = {10.1097/WNO.0b013e3182589589},
	author = {Sham, Caroline W and Chan, Ann M and Kwong, Jacky M K and Caprioli, Joseph and Nusinowitz, Steven and Chen, Bryan and Lee, Janice G and Gandhi, Nishant M and Francisco, Loise M and Sharpe, Arlene H and Chen, Ling and Braun, Jonathan and Gordon, Lynn K}
}
