TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly and can be classified either as dry or as neovascular (or wet). Neovascular AMD is characterized by a strong immune response and the inadequate release of cytokines triggering angiogenesis and induction of photoreceptor death. The pathomechanisms of AMD are only partly understood. Here, we identify the endolysosomal two-pore cation channel TPC2 as a key factor of neovascularization and immune activation in the laser-induced choroidal neovascularization (CNV) mouse model of AMD. Block of TPC2 reduced retinal VEGFA and IL-1 beta levels and diminished neovascularization and immune activation. Mechanistically, TPC2 mediates cationic currents in endolysosomal organelles of immune cells and lack of TPC2 leads to reduced IL-1 beta levels in areas of choroidal neovascularization due to endolysosomal trapping. Taken together, our study identifies TPC2 as a promising novel therapeutic target for the treatment of AMD.

Automated summary

Age-related macular degeneration (AMD) is a common cause of blindness among the elderly, classified as dry or neovascular. Research shows that the endolysosomal two-pore cation channel TPC2 plays a key role in neovascularization and immune activation in AMD, and blocking TPC2 can reduce related factors levels in the pathological process of AMD.