https://scholars.lib.ntu.edu.tw/handle/123456789/568943
標題: | TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration | 作者: | Li, Yanfen Schön, Christian CHENG-CHANG CHEN Yang, Zhuo Liegl, Raffael Murenu, Elisa Schworm, Benedikt Klugbauer, Norbert Grimm, Christian Wahl-Schott, Christian Michalakis, Stylianos Biel, Martin |
公開日期: | 八月-2021 | 卷: | 4 | 期: | 8 | 來源出版物: | Life science alliance | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/568943 | ISSN: | 2575-1077 | DOI: | 10.26508/lsa.202101047 |
顯示於: | 醫學檢驗暨生物技術學系 |
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