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Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis
Author(s) -
Cappelli Holly C.,
Guarino Brianna D.,
Kanugula Anantha K.,
Adapala Ravi K.,
Perera Vidushani,
Smith Matthew A.,
Paruchuri Sailaja,
Thodeti Charles K.
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30116
Subject(s) - trpv4 , angiogenesis , transient receptor potential channel , retinal , microbiology and biotechnology , retina , pericyte , biology , mechanosensitive channels , neovascularization , retinal pigment epithelium , endothelial stem cell , receptor , cancer research , neuroscience , ion channel , biochemistry , in vitro
Transient receptor potential vanilloid 4 (TRPV4) channels are mechanosensitive ion channels that regulate systemic endothelial cell (EC) functions such as vasodilation, permeability, and angiogenesis. TRPV4 is expressed in retinal ganglion cells, Müller glia, pigment epithelium, microvascular ECs, and modulates cell volume regulation, calcium homeostasis, and survival. TRPV4‐mediated physiological or pathological retinal angiogenesis remains poorly understood. Here, we demonstrate that TRPV4 is expressed, functional, and mechanosensitive in retinal ECs. The genetic deletion of TRPV4 did not affect postnatal developmental angiogenesis but increased pathological neovascularization in response to oxygen‐induced retinopathy (OIR). Retinal vessels from TRPV4 knockout mice subjected to OIR exhibited neovascular tufts that projected into the vitreous humor and displayed reduced pericyte coverage compared with wild‐type mice. These results suggest that TRPV4 is a regulator of retinal angiogenesis, its deletion augments pathological retinal angiogenesis, and that TRPV4 could be a novel target for the development of therapies against neovascular ocular diseases.