TY - JOUR T1 - TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101047 VL - 4 IS - 8 SP - e202101047 AU - Yanfen Li AU - Christian Schön AU - Cheng-Chang Chen AU - Zhuo Yang AU - Raffael Liegl AU - Elisa Murenu AU - Benedikt Schworm AU - Norbert Klugbauer AU - Christian Grimm AU - Christian Wahl-Schott AU - Stylianos Michalakis AU - Martin Biel Y1 - 2021/08/01 UR - https://www.life-science-alliance.org/content/4/8/e202101047.abstract N2 - 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-1β 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-1β 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. ER -