Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea

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.

 

Comments：

In this study, the researchers investigated the role of transient receptor potential vanilloid 4 (TRPV4) in the development of neovascularization in the corneal stroma following cauterization injury in mice. Neovascularization can lead to stromal opacification and curvature disturbance, which can impair visual function. The researchers found that loss of TRPV4 expression suppressed the growth of CD31-labeled neovascularization, along with the infiltration of macrophages and the expression of vascular endothelial cell growth factor A mRNA.

To further confirm the role of TRPV4 in neovascularization, the researchers conducted in vitro experiments using cultured vascular endothelial cells. They found that treatment with a TRPV4 antagonist, HC-067047, attenuated the formation of tube-like structures that modeled new vessel formation.

The findings of this study suggest that TRPV4 is involved in injury-induced macrophagic inflammation and neovascularization activity in the mouse corneal stroma. Thus, TRPV4 could be a potential therapeutic target for preventing unfavorable post-injury neovascularization in the cornea.

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