TPC2 Promotes Choroidal Angiogenesis and Inflammation in a Mouse Model of Neovascular Age-related Macular Degeneration

Overview

Journal Life Sci Alliance

Specialties Biochemistry
Biology
Cell Biology
Molecular Biology

Date 2021 Jun 29

PMID 34183443

Citations 10

Authors

Yanfen Li

Christian Schon

Cheng-Chang Chen

Zhuo Yang

Raffael Liegl

Elisa Murenu

Benedikt Schworm

Norbert Klugbauer

Christian Grimm

Christian Wahl-Schott

Stylianos Michalakis

Martin Biel

Affiliations

Soon will be listed here.

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-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.

Citing Articles

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Electrophysiological Techniques on the Study of Endolysosomal Ion Channels.

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PMID: 36871125 DOI: 10.1007/164_2023_638.

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