Purchase this article with an account.
Ann M. Chan, Caroline W. Sham, Janice G. Lee, Deanna J. Leon, Jonathan Braun, Lynn K. Gordon; Programmed Death Ligands Are Expressed in Multiple Retinal Cell Types and Modulates Retinal Ganglion Cell Loss During Maturation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5352. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Retinal maturation requires developmentally-associated retinal ganglion cell death in the postnatal mouse. We previously observed that the immunoregulatory receptor, programmed cell death-1 (PD-1) acts to actively promote retinal ganglion cell (RGC) death during murine postnatal retina maturation. The goal of this study is to identify retinal expression of PD-ligands and determine whether they play a role in promoting RGC death during retinal maturation.
C57BL/6 mice or animals who lacked PD-1 or its ligand(s) in a C57BL/6 background were studied including PD-1 knockout (PD-1 -/-), PD-L1 knockout (PD-L1 -/-), PD-L2 knockout (PD-L2 -/-), and PD-L1/L2 double knockout (DKO). Immunofluorescence (IF) staining using antibodies against specific markers was used to identify cell types expressing PD-ligand(s) in the wild type mouse retina. Quantification of RGCs and amacrine cells in the retina was performed at various postnatal ages in the knockout animals. Quantification of optic nerve axons from PD-1 KO, PD-L1/L2 DKO, and wild-type adult mice were obtained from electron microscopy images.
PD-L1 expression is found throughout the neonatal retina and expression is identified in adult RGCs, bipolar interneurons and Müller glia. In the absence of both PD-ligands (DKO), but PD-L1 expression is found throughout the neonatal retina and expression is identified in adult RGCs, bipolar interneurons and Müller glia. In the absence of both PD-ligands (DKO), but not in either the single knockout for PD-L1 or PD-L2, there is a significant numerical increase in RGCs in the neonatal retina (34% at P2 [p=0.006]) and in the adult retina (18% [p≤0.04]), as compared to wild type.
This work identifies PD-L1 expression in neural retina and is concordant with our prior studies, which supports a role for the PD-1/PD-ligand interaction in developmental RGC culling. In contrast to PD-1 knockout, in which there is a transient numerical increase in RGC cell number, the PD ligand DKO exhibited persistent increase in RGC cell numbers into adulthood. These data collectively support a novel role for active promotion of neuronal cell death through a PD-1 receptor-ligand engagement.
This PDF is available to Subscribers Only