TLR2 signaling contributes to the angiogenesis of oxygen-induced retinopathy.

Abstract Purpose To evaluate the role of Toll-like receptor 2 (TLR2) signaling in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Materials and methods The OIR model was established in C57BL/6J wild type (WT) mice and TLR2−/− mice. Retinal neovascularization in the OIR model was measured by counting new vascular cell nuclei above the internal limiting membrane and analyzing flat-mounted retinas perfused with fluorescein dextran and immunostained with Griffonia Simplicifolia (GS) isolectin. The expression of TLR2 and VEGF in the retina was detected by immunofluorescence. Expression of TGF- β1, b-FGF, and IL-6 mRNA in the retina was measured by quantitative real-time PCR. Results Compared to WT OIR mice, retinal neovascularization was attenuated in TLR2−/− OIR mice. The co-expressions of TLR2 and VEGF were remarkably and consistently increased in WT OIR mice; however, there was no expression of TLR2 and a significant decrease in VEGF expression in TLR2−/− OIR mice. These results suggest that TLR2 plays a central role in OIR model angiogenesis. Expression of TGF- β1, b-FGF, and IL-6 mRNA were reduced in the TLR2−/− OIR mice, suggesting that the inflammatory response induced by TLR2 relates to angiogenesis. Conclusion TLR2 signaling in the retina is associated with neovascularization in mice. Inflammation contributes to the activation of angiogenesis and is partially mediated through the TLR2-VEGF retinal signaling pathway.