Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan.
Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan.
Lab Invest. 2023 May;103(5):100061. doi: 10.1016/j.labinv.2022.100061. Epub 2023 Jan 10.
Corneal injury-associated inflammation could induce inward-growing neovascularization from the periphery of the tissue. Such neovascularization could cause stromal opacification and curvature disturbance, and both potentially impair visual function. In this study, we determined the effects of the loss of transient receptor potential vanilloid 4 (TRPV4) expression on the development of neovascularization in the corneal stroma in mice by producing a cauterization injury in the central area of the cornea. New vessels were immunohistochemically labeled with anti-TRPV4 antibodies. TRPV4 gene knockout suppressed the growth of such CD31-labeled neovascularization in association with the suppression of infiltration of macrophages and tissue messenger RNA expression of the vascular endothelial cell growth factor A level. Treatment of cultured vascular endothelial cells with supplementation of HC-067047 (0.1 μM, 1 μM, or 10 μM), a TRPV4 antagonist, attenuated the formation of a tube-like structure with sulforaphane (15 μM, for positive control) that modeled the new vessel formation. Therefore, the TRPV4 signal is involved in injury-induced macrophagic inflammation and neovascularization activity by vascular endothelial cells in a mouse corneal stroma. TRPV4 could be a therapeutic target to prevent unfavorable postinjury neovascularization in the cornea.
角膜损伤相关的炎症可能会导致组织边缘的内向生长的新生血管。这种新生血管可能会导致基质混浊和曲率紊乱，从而潜在地损害视觉功能。在这项研究中，我们通过在角膜中央区域制造烧灼伤，确定了瞬时受体电位香草酸 4 (TRPV4) 表达缺失对小鼠角膜基质中新生血管形成的影响。用抗 TRPV4 抗体对新血管进行免疫组织化学标记。TRPV4 基因敲除抑制了这种 CD31 标记的新生血管的生长，同时抑制了巨噬细胞的浸润和血管内皮细胞生长因子 A 水平的组织信使 RNA 表达。用 TRPV4 拮抗剂 HC-067047（0.1 μM、1 μM 或 10 μM）处理培养的血管内皮细胞，可减轻与阳性对照物（15 μM 的 sulforaphane）建模的新血管形成的管样结构的形成。因此，TRPV4 信号参与了小鼠角膜基质中损伤诱导的巨噬细胞炎症和血管内皮细胞的新生血管活性。TRPV4 可能是预防角膜损伤后不利的新生血管形成的治疗靶点。
