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Published on: December 4, 2007
Protective effects of blocking PD-1 pathway on retinal ganglion cells in a mouse model of chronic ocular hypertension
Siqi Sheng1,2,3,4, Yixian Ma1,2,3,4, Yue Zou1,2,3,4
1Department of Ophthalmology & Vision Science, Eye & Ears, Nose and Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
Purpose:
In this study, we aimed to investigate whether Programmed cell death 1 ligand 1/programmed cell death 1 ligand 2 (PD-L1/PD-L2) double knockout (dKO) has a protective effect on RGCs in a mouse model of chronic ocular hypertension (COHT).
Methods:
We used superparamagnetic iron oxide to induce COHT in mice. Apoptosis of retinal ganglion cells (RGCs) and activation of microglia were evaluated using western blotting (WB) and immunofluorescence staining of the mouse retina. In addition, we also conducted transcriptome sequencing and further gene expression analyses using the gene ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) database.
Results:
In the mouse model of COHT, PD-L1/PD-L2 prevented the apoptosis of RGCs to some extent. Blocking the programmed cell death 1 (PD-1) pathway also increased the number of anti-inflammatory M2-activated microglia and enhanced the phosphorylation of its related pathway signal transducer and activator of transcription (STAT)6. Sequencing results showed that this protective effect may have been achieved by regulating the NF-B, tumour necrosis factor (TNF), PI3K/Akt and toll-like receptor signaling pathway etc.
Conclusion:
Blocking the PD-1 pathway has a protective effect on RGCs in the mouse model of COHT induced by superparamagnetic iron oxide.
Insights
Blocking the PD-1 pathway protects retinal ganglion cells (RGCs) in a mouse model of chronic ocular hypertension (COHT). This intervention reduces RGC apoptosis and promotes anti-inflammatory microglia activation, suggesting a therapeutic benefit.
Area of Science:
- Ophthalmology
- Immunology
- Neuroscience
Background:
- Chronic ocular hypertension (COHT) is a leading cause of optic nerve damage and vision loss.
- Retinal ganglion cells (RGCs) are crucial for vision and are vulnerable to damage in glaucoma and COHT.
- The programmed cell death 1 (PD-1) pathway plays a role in immune regulation and has been implicated in various disease processes.
Purpose of the Study:
- To investigate the protective effect of Programmed cell death 1 ligand 1/programmed cell death 1 ligand 2 (PD-L1/PD-L2) double knockout (dKO) on RGCs in a mouse model of chronic ocular hypertension (COHT).
- To evaluate the impact of blocking the PD-1 pathway on RGC apoptosis and microglial activation in the context of COHT.
Main Methods:
- Induction of COHT in mice using superparamagnetic iron oxide.
- Assessment of RGC apoptosis and microglial activation via western blotting and immunofluorescence staining.
- Transcriptome sequencing and gene expression analysis (GO, KEGG) to identify underlying molecular pathways.
Main Results:
- PD-L1/PD-L2 dKO partially prevented RGC apoptosis in the COHT mouse model.
- Blocking the PD-1 pathway increased the number of anti-inflammatory M2-activated microglia.
- Enhanced phosphorylation of STAT6 and regulation of NF-κB, TNF, PI3K/Akt, and toll-like receptor signaling pathways were observed.
Conclusions:
- Blocking the PD-1 pathway demonstrates a protective effect on RGCs in a mouse model of COHT.
- The findings suggest that targeting the PD-1 pathway may be a viable therapeutic strategy for protecting RGCs in conditions like glaucoma.
