Prominin-1 Regulates Retinal Pigment Epithelium Homeostasis: Transcriptomic Insights into Degenerative Mechanisms

Area of Science:

• Ophthalmology
• Cell Biology
• Genetics

Background:

• Inherited retinal degenerations (IRDs) and atrophic age-related macular degeneration (aAMD) share retinal pigment epithelium (RPE) dysfunction.
• The role of Prominin-1 (Prom1) in RPE homeostasis is not well understood, despite its known association with photoreceptor pathology.

Purpose of the Study:

• To investigate the function of Prominin-1 (Prom1) in retinal pigment epithelium (RPE) cells.
• To identify signaling pathways regulated by Prominin-1 (Prom1) in RPE.

Main Methods:

• Assessed Prominin-1 (Prom1) expression in mouse retina and RPE.
• Generated Prominin-1 (Prom1)-knockout RPE cells using CRISPR/Cas9.
• Performed bulk RNA sequencing and gene set enrichment analysis (GSEA).

Main Results:

• Prominin-1 (Prom1)-knockout RPE cells showed altered expression of key genes including Grem1, Slc7a11, and IL33.
• Reduced expression of mitophagy (PINK1) and phagocytosis (MerTK) markers was observed.
• Activated pathways included E2F/MYC targets and mTORC1 signaling; suppressed pathways involved apical junctions and EMT.

Conclusions:

• Prominin-1 (Prom1) is vital for maintaining RPE integrity by regulating stress responses, mitochondrial turnover, phagocytosis, and cell junctions.
• Prominin-1 (Prom1)-dependent signaling networks offer mechanistic insights into RPE degeneration in IRD and aAMD.
• Prominin-1 (Prom1) represents a potential therapeutic target for retinal diseases.