Journal
EXPERIMENTAL EYE RESEARCH
Volume 228, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2023.109405
Keywords
AQP4; Retinal edema; Retinal vein occlusion; TRPV4; Vascular permeability; VEGF
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This study investigated the role of TRPV4 in retinal vascular disease. TRPV4 expression and localization were examined in a mouse model of retinal vein occlusion (RVO). The effects of TRPV4 antagonists on retinal edema, blood flow, and ischemic areas were evaluated in RVO mice.
This study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4), a calcium (Ca2+)-permeable cation channel, in the pathophysiology of retinal vascular disease. The retinal vein occlusion (RVO) murine model was created by irradiating retinal veins using lasers. TRPV4 expression and localization were evaluated in RVO mice retinas. In addition, we examined the effects of TRPV4 antagonists (RQ-00317310, HC-067047, GSK2193874, and GSK2798745) on retinal edema, blood flow, and ischemic areas in RVO mice. Furthermore, changes in the retinal expression of tumor necrosis factor (TNF)-alpha and aquaporin4 (AQP4) by RQ-00317310 were analyzed using Western blot. We also assessed the barrier integrity of epithelial cell monolayers using trans-endothelial electrical resistance (TEER) in Human Retinal Microvascular Endothelial Cells (HRMECs). The expression of TRPV4 was significantly increased and co-localized with glutamine synthetase (GS), a Muller glial marker, in the ganglion cell layer (GCL) of the RVO mice. Moreover, RQ-00317310 admin-istration ameliorated the development of retinal edema and ischemia in RVO mice. In addition, the up regulation of TNF-alpha and down-regulation of AQP4 were lessened by the treatment with RQ-00317310. Treatment with GSK1016790A, a TRPV4 agonist, increased vascular permeability, while RQ-00317310 treatment decreased vascular endothelial growth factor (VEGF)-or TRPV4-induced retinal vascular hyperpermeability in HRMECs. These findings suggest that TRPV4 plays a role in the development of retinal edema and ischemia. Thus, TRPV4 could be a new therapeutic target against the pathological symptoms of retinal vascular diseases.
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