Purchase this article with an account.
Hiroki Iwanishi, Takayoshi Sumioka, Yuka Okada, Osamu Yamanaka, Shizuya Saika; Lacking Smad3 attenuates development of Argon laser-induced CNV in mice.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1196.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effects of lacking Smad3 on the development of experimental choroidal neovascularization (CNV) following argon-laser irradiation in mice. Roles of ALK1 and ALK 5 in vascular formation were examined in cell culture.
Male wild type (WT) and Smad3-null (KO) mice of 8-12 week-old were used. (1) Argon laser-photocoagulation (5 shots, 75 μm spot size, 0.1 sec. duration, 150 mW) was performed in an eye of WT (n = 5) and KO (n = 5) mice. The size of CNV was measured at 2 weeks by software-assisted fluorescence angiography after sacrifice and enucleation. (2) Laser photocoagulation (15 shots) was performed in an eye of WT (n = 5) and KO (n = 5) mice. Total RNA was extracted from retino-choroidal tissue at day 3 post-treatment. Real-time RT-PCR was ran for mRNAs of VEGF, IL-6, F4/80 macrophage antigen, TGFb1 and MCP-1. (3) Effects of adding an ALK5 inhibitor (SB431542) on CD31-labeled vessel-like structure formation by HUVECs in a co-culture system with fibroblast feeder layer.
Laser-induced CNV formation was dramatically suppressed by lacking Smad3 in mice. Loss of Smad3 suppressed mRNA expression of VEGF, IL-6 and F4/80 in retino-choroidal tissue. TGFb1-accelerated neovascularization (vessel-like structure formation) by HUVECs was further augmented by adding an ALK5 inhibitor SB431542, suggesting ALK5/Smad3 signal counteracts neovascularization promotion of HUVECs in cell culture condition.
Blocking TGFb/Smad3 signaling is a potential strategy for therapeutic approach to CNV-related disorders, including AMD by interfering macrophage-related inflammation.
This PDF is available to Subscribers Only