Purchase this article with an account.
Hyun Beom Song, Hyoung Oh Jun, Jin Hyoung Kim, Inho Jo, Jeong Hun Kim; Blockade of transient receptor potential (TRP) channels inhibits retinal neovascularization via inhibition of calcium ion dependent signaling pathway. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5614.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The aim of this study is to investigate whether blockade of transient receptor potential (TRP) channels inhibits retinal neovascularization in the mouse model of oxygen induced retinopathy.
The expressions of TRP channel isoforms on mouse retina and human renal microvascular endothelial cells (HRMECs) were evaluated by RT-PCR. The anti-angiogenic activity of TRP channel inhibitors and calcium ion chelators was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration and in vitro tube formation assay of HRMECs. In the mouse model of oxygen induced retinopathy, calcium ion level was evaluated by TOF-SIMS, and retinal neovascularization was evaluated after intraocular injection of TRP channel inhibitors and calcium ion chelators, whose effect on MAPK signaling pathway was evaluated by Western blot analysis.
TRP channel 1, 4 and 6 were strongly expressed on mouse retina and HRMECs. TRP channel inhibitor, SKF 96365 and 2-APB, and calcium ion chelators, BAPTA, effectively suppressed VEGF-induced in vitro angiogenesis of HRMECs including proliferation, migration and tube formation, respectively. In the mouse model of oxygen induced retinopathy, calcium ion was increased at inner retina during neovascularization, and intraocular injection of TRP channel inhibitor, SKF 96365 and 2-APB, and calcium ion chelators, BAPTA, significantly inhibited retinal neovascularization, which also modulated ERK-1/2 signaling pathway.
Calcium ion dependent signaling pathways mediated by TRP channels are involved in retinal angiogenesis. Furthermore, inhibiting retinal neovascularization by blockade of TRP channels could be extensively applied to variable vaso-proliferative retinopathies.
This PDF is available to Subscribers Only