TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration
| العنوان: | TPC2 promotes choroidal angiogenesis and inflammation in a mouse model of neovascular age-related macular degeneration |
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| المؤلفون: | Yanfen Li, Zhuo Yang, Norbert Klugbauer, Christian Schön, Stylianos Michalakis, Raffael Liegl, Christian Grimm, Benedikt Schworm, Martin Biel, Christian Wahl-Schott, Elisa Murenu, Cheng-Chang Chen |
| المصدر: | Life Science Alliance |
| بيانات النشر: | Life Science Alliance LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Vascular Endothelial Growth Factor A, genetic structures, Angiogenesis, Health, Toxicology and Mutagenesis, Interleukin-1beta, Inflammation, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Retina, Cell Line, Neovascularization, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, medicine, Animals, Humans, Fluorescein Angiography, Research Articles, Ecology, business.industry, Lasers, Retinal, Macular degeneration, medicine.disease, eye diseases, Vascular endothelial growth factor A, Disease Models, Animal, 030104 developmental biology, Choroidal neovascularization, chemistry, Cancer research, Wet Macular Degeneration, sense organs, Calcium Channels, medicine.symptom, business, Lysosomes, 030217 neurology & neurosurgery, Research Article |
| الوصف: | This study identifies the endolysosomal two-pore channel TPC2 as a potential novel drug target for age-related macular degeneration (AMD). Inhibition of TPC2 reduces two key clinical hallmarks of the AMD, retinal inflammation and formation of leaky choroi. 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. |
| اللغة: | English |
| تدمد: | 2575-1077 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b111334d1ecefec51f1eb3e7f9137d9Test http://europepmc.org/articles/PMC8321671Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2b111334d1ecefec51f1eb3e7f9137d9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25751077 |
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