Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis
| Autor: | Anantha K Kanugula, Holly C. Cappelli, Charles K. Thodeti, Vidushani Perera, Sailaja Paruchuri, Ravi K. Adapala, Brianna D. Guarino, Matthew A. Smith |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
TRPV4 Physiology Angiogenesis Clinical Biochemistry Neovascularization Physiologic TRPV Cation Channels Retinal Neovascularization Biology Mechanotransduction Cellular Retinal ganglion Retina Article Neovascularization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Humans Endothelial Cells Retinal Cell Biology eye diseases Cell biology Mice Inbred C57BL Oxygen Endothelial stem cell 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Microvessels Mechanosensitive channels sense organs medicine.symptom Pericytes Muller glia Gene Deletion |
| Zdroj: | J Cell Physiol |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.30116 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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