Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis,Journal of Cellular Physiology

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Transient receptor potential vanilloid 4 channel deletion regulates pathological but not developmental retinal angiogenesis
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-10-20 , DOI: 10.1002/jcp.30116
Holly C Cappelli _{1,

2} , Brianna D Guarino ₁ , Anantha K Kanugula ₁ , Ravi K Adapala _{1,

2} , Vidushani Perera ₁ , Matthew A Smith _{3,

4} , Sailaja Paruchuri ₅ , Charles K Thodeti _{1,

2}

Affiliation

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.

中文翻译：

瞬时受体电位香草酸4通道缺失调节病理性而非发育性视网膜血管生成

瞬时受体电位香草酸 4 (TRPV4) 通道是机械敏感离子通道，可调节全身内皮细胞 (EC) 功能，如血管舒张、通透性和血管生成。 TRPV4 在视网膜神经节细胞、穆勒胶质细胞、色素上皮、微血管 EC 中表达，并调节细胞体积调节、钙稳态和存活。 TRPV4 介导的生理或病理性视网膜血管生成仍然知之甚少。在这里，我们证明 TRPV4 在视网膜 EC 中表达、有功能且具有机械敏感性。 TRPV4 的基因缺失并不影响出生后发育性血管生成，但会增加对氧诱导性视网膜病变 (OIR) 的病理性新生血管形成。与野生型小鼠相比，接受 OIR 处理的 TRPV4 敲除小鼠的视网膜血管表现出投射到玻璃体液中的新生血管簇，并且周细胞覆盖率降低。这些结果表明TRPV4是视网膜血管生成的调节因子，其缺失会增强病理性视网膜血管生成，并且TRPV4可能成为开发针对新生血管性眼部疾病的疗法的新靶标。

更新日期：2020-10-20

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