Suppression ofIn VivoNeovascularization by the Loss of TRPV1 in Mouse Cornea

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.

Endothelial TRPV1 as an Emerging Molecular Target to Promote Therapeutic Angiogenesis

“…In agreement with this observation, blocking TRPV1 with capsazepine and A784168 inhibited neovascularization in a mouse model of oxygen-induced retinopathy [89]. Moreover, while pharmacological inhibition of TRPV1 with the selective antagonist SBB366791 did not prevent VEGF-induced tube formation in HUVEC, genetic deletion of TRPV1 abrogated stromal neovascularization in an in vivo cornea after a cauterization injury at the central cornea [158]. Consistently, the expression of pro-inflammatory/angiogenic factors (i.e., transforming growth factor β1 (TGFβ1) and VEGF) was suppressed in TRPV1-knockout (TRPV1 −/− ) mice [158].…”

“…Moreover, while pharmacological inhibition of TRPV1 with the selective antagonist SBB366791 did not prevent VEGF-induced tube formation in HUVEC, genetic deletion of TRPV1 abrogated stromal neovascularization in an in vivo cornea after a cauterization injury at the central cornea [158]. Consistently, the expression of pro-inflammatory/angiogenic factors (i.e., transforming growth factor β1 (TGFβ1) and VEGF) was suppressed in TRPV1-knockout (TRPV1 −/− ) mice [158]. Thus, targeting TRPV1 could provide an effective strategy to treat severe ischemic disorders.…”

Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes

“…Even though the cognate VEGF receptor (VEGFR) and TRPV1 are coexpressed on corneal fibroblasts ( 53 ), it is unclear if the Ca 2+ transients mediating VEGF-induced stromal angiogenesis stem from VEGFR-mediated activation of TRPV1 ( 13 , 54 , 55 ). A clear indication that neovascularization and the increased expression of VEGF following corneal chemical injury may depend on TRPV1 expression, is that those tissue responses were markedly attenuated in TRPV1 knockout mice ( 53 ). Besides neovascularization, VEGF upregulation contributes to increased endothelial cell proliferation and migration in a bovine wound healing model ( 56 , 57 ).…”

CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing

“…Suppression of in vivo neovascularization was demonstrated by Tomoyose et al, in a Trpv1 gene knock out mice. After the induction of a cauterization injury at the central cornea, they showed that, in the absence of TRPV1, stromal neovascularization was inhibited, probably secondary to lower levels of both TGFβ-1 and vascular endothelial growth factor [ 43 ].…”