Abstract
Purpose: :
Tetrac (tetraiodothyroacetic acid) is a deaminated analogue of L-thyroxine (T4)) that blocks the pro-angiogenesis actions of (T4) and 3, 5, 3'-triiodo-L-thyronine as well as VEGF and FGF-2 by a mechanism involving integrin alphaVbeta3. We investigated the potential anti-angiogenic activity of tetrac on retinal angiogenesis in vitro and vivo.
Methods: :
Human retinal endothelial cells (HREC) were treated with or without tetrac and stimulatory factors, and ERK1/2 phosphorylation assessed by western blotting. The oxygen-induced retinopathy model (OIR) was used, in which newborn mice are exposed to hyperoxia from postnatal day 7 (P7) to P12 and then returned to room air. Tetrac was administered by intravitreal injection at P12 and P15, and vehicle was used as control. Retinal neovascularization was assessed at P18.
Results: :
Tetrac significantly inhibited the activation of ERK1/2by both VEGF and T4 treatmentin HREC. In the mouse OIR model, intravitreal injection of tetrac significantly reduced pathological retinal neovascularization at P18 as compared to vehicle. Tetrac did not have a significant effect on avascular retinal area.
Conclusions: :
Our study demonstrates the antiangiogenic effects of Tetrac in retinal neovascularization in vitro and in vivo. Tetrac could be used as a therapeutic agent for retinal neovascularization.
Keywords: retinal neovascularization • neovascularization • drug toxicity/drug effects