PDGF-D-induced immunoproteasome activation and cell-cell interactions

Area of Science:

• Ophthalmology
• Immunology
• Cell Biology

Background:

• Platelet-derived growth factor-D (PDGF-D) is prevalent in ocular diseases.
• Its specific role in ocular cell function and interaction remains unclear.

Purpose of the Study:

• To investigate the impact of PDGF-D on retinal pigment epithelial (RPE) cells and ocular tissues.
• To explore the therapeutic potential of targeting the PDGF-D pathway in neovascular eye diseases.

Main Methods:

• Utilized single-cell RNA sequencing (scRNA-seq) in a mouse model with PDGF-D overexpression in RPE cells.
• Analyzed ligand-receptor interactions and cell-cell communication.
• Administered an immunoproteasome inhibitor (ONX-0914) in a mouse model of choroidal neovascularization (CNV).

Main Results:

• PDGF-D overexpression upregulated immunoproteasome genes in RPE cells, enhancing antigen processing and presentation.
• Significant increase in ligand-receptor pairs indicated heightened cell-cell interactions.
• Detected a novel cell population suggesting PDGF-D-induced RPE epithelial-mesenchymal transition.
• ONX-0914 treatment suppressed choroidal neovascularization in vivo.

Conclusions:

• PDGF-D overexpression promotes pro-angiogenic immunoproteasome activity and alters RPE cell behavior.
• Targeting the immunoproteasome pathway presents a potential therapeutic strategy for neovascular eye conditions.