Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 236, Issue 5, Pages 3770-3779Publisher
WILEY
DOI: 10.1002/jcp.30116
Keywords
ECM stiffness; human retinal endothelial cells; mechanotransduction; neovascularization; TRPV4
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Funding
- National Institutes of Health [R01AI144115, R01HL119705, R01HL148585, R15CA202847]
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TRPV4 channels regulate endothelial cell functions in the retina, with their deletion leading to increased pathological neovascularization. This suggests that TRPV4 could be a potential target for therapies against neovascular ocular diseases.
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, Muller 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.
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