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

Li, Yanfen; Schoen, Christian; Chen, Cheng-Chang; Yang, Zhuo; Liegl, Raffael; Murenu, Elisa; Schworm, Benedikt; Klugbauer, Norbert; Grimm, Christian; Wahl-Schott, Christian; Michalakis, Stylianos und Biel, Martin (2021): TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration. In: Life Science Alliance, Bd. 4, Nr. 8, e202101047

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• Sprache: Englisch