Suppression of In Vivo Neovascularization by the Loss of TRPV1 in Mouse Cornea.

Katsuo Tomoyose,Takayoshi Sumioka,Masayasu Miyajima,Kumi Shirai,Kathleen C Flanders,Shizuya Saika,Tomoya Morii,Yuka Okada,Peter S Reinach,Osamu Yamanaka

doi:10.1155/2015/706404

Abstract

To investigate the effects of loss of transient receptor potential vanilloid receptor 1 (TRPV1) on the development of neovascularization in corneal stroma in mice. Blocking TRPV1 receptor did not affect VEGF-dependent neovascularization in cell culture. Lacking TRPV1 inhibited neovascularization in corneal stroma following cauterization. Immunohistochemistry showed that immunoreactivity for active form of TGFβ1 and VEGF was detected in subepithelial stroma at the site of cauterization in both genotypes of mice, but the immunoreactivity seemed less marked in mice lacking TRPV1. mRNA expression of VEGF and TGFβ1 in a mouse cornea was suppressed by the loss of TRPV1. TRPV1 gene ablation did not affect invasion of neutrophils and macrophage in a cauterized mouse cornea. Blocking TRPV1 signal does not affect angiogenic effects by HUVECs in vitro. TRPV1 signal is, however, involved in expression of angiogenic growth factors in a cauterized mouse cornea and is required for neovascularization in the corneal stroma in vivo.

Highlights

The cornea is a unique ocular tissue of avascularity and transparency for proper vision
The present experiments first showed that lacking transient receptor potential vanilloid receptor 1 (TRPV1) cation channel receptor suppressed stromal neovascularization in an in vivo mouse cornea following receiving a cauterization injury at the central cornea
Cell culture experiment showed that blockage of TRPV1 receptor did not affect vascular endothelial growth factor (VEGF) angiogenic action on human umbilical vein endothelial cell (HUVEC)

Summary

Introduction

The cornea is a unique ocular tissue of avascularity and transparency for proper vision. It is susceptible to neovascularization-inducing intervention, that is, microbial infection or ocular surface damage. The process of the new vessel formation in an injured cornea is orchestrated by a complex system of various growth factor signaling [1,2,3,4,5]. Resident corneal cells and inflammatory cells invaded to an injured tissue express growth factors and cytokines involved in injury-induced neovascularization. Such factors include vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ), and fibroblast growth factor (FGF) [6,7,8,9,10]

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Results

Conclusion