Related Experiment Video
Updated: Apr 5, 2026
Examination of Anatomical Features of Retinal Ganglion Cells Under N-methyl-D-aspartic Acid (NMDA)-induced Excitotoxicity
Published on: September 19, 2025
Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush
1Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States; Fudan Affiliated Eye and ENT Hospital, Fenyang Road 83#, Shanghai 200031, China.
Abstract:
Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.
Insights
Programmed cell death-1 (PD-1) is upregulated in retinal ganglion cells (RGCs) after optic nerve crush (ONC). This study investigates PD-1 regulation in RGCs following injury, suggesting a role in RGC survival or death.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Programmed cell death-1 (PD-1) is a key inhibitory receptor found on immune cells.
- PD-1 ligation has been shown to induce retinal ganglion cell (RGC) death during retinal development.
- The role of PD-1 in RGCs following injury remains largely uncharacterized.
Purpose of the Study:
- To investigate the regulation and expression patterns of PD-1 in the retina after optic nerve crush (ONC).
- To determine if PD-1 is expressed in RGCs following retinal injury and its potential correlation with cell death markers.
Main Methods:
- C57BL/6 mice underwent ONC, and RGC loss was assessed using Rbpms immunolabelling.
- PD-1 mRNA expression was quantified using real-time PCR.
- PD-1 protein expression was visualized and quantified via immunofluorescence staining on whole mount retinas, with analysis of colocalization with cleaved-caspase-3.
Main Results:
- PD-1 gene expression significantly increased from day 1 to day 14 post-ONC.
- Immunofluorescence revealed a substantial rise in PD-1 expression in injured retinas.
- PD-1 was predominantly expressed in a subset of larger RGCs, with an 82% increase in staining intensity compared to controls; these cells did not exhibit cleaved-caspase-3 at day 5 post-injury.
Conclusions:
- This study provides the first evidence of PD-1 induction in RGCs following ONC.
- The findings suggest that PD-1 expression in RGCs after injury warrants further investigation into its role in RGC survival and death pathways.
