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C. W. Sham, J. M. K. Kwong, A. M. Chan, J. G. Lee, J. Caprioli, J. Braun, L. K. Gordon; Characterization of the PD-1 Expression Pattern After Optic Nerve Transection in the Rat. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6109.
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© ARVO (1962-2015); The Authors (2016-present)
Understanding cellular signals that trigger retinal ganglion cell (RGC) death may help guide development of new therapeutic approaches. Programmed cell death-1 (PD-1) is a membrane receptor expressed in rodent RGCs and a subpopulation of amacrine cells. Engagement of PD-1 with its ligand promotes developmental RGC death in mice. We hypothesize that PD-1 ligation could trigger RGC death following optic nerve transection (ONT). This study characterizes retinal PD-1 expression in the setting of optic nerve injury using a rat ONT model.
Left optic nerves of adult male Wistar rats (4 animals per group) were transected and fluorogold (FG) retrograde tracer was applied to the transected nerve to identify RGCs; right eyes served as uninjured controls. At 14 days following ONT >95% of RGCs die whereas amacrine cells survive prompting a time course study at 1, 3, 7, and 14 days post-ONT. Vertical retinal sections were stained with anti-PD-1 and serial sections were analyzed using epifluorescent images. All ganglion cell layer (GCL) cells were scored for positivity of PD-1, FG, and RGC morphology by two independent blinded investigators. Statistical analysis was performed using Pearson correlation coefficients and two-tailed p-values.
At day 1 post-ONT 84% of the FG+ cells are positive for PD-1. At day 14 the majority of FG+ cells resemble activated microglia by morphology and only 52% are positive for PD-1. In comparison to day 1, FG+ RGCs were decreased by 97% at day 14, and 73% of these cells are PD-1 positive. Over the ONT time course, the decrease in PD-1 expression correlates with loss of RGCs (p<0.05), but not with the FG negative GCL cells.
PD-1 expression changes during the process of ONT-induced RGC death. Additional studies are needed to fully define the role of PD-1 ligation as a trigger for RGC death following injury.
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