Yuying Sun1, Yao Ni2, Ning Kong3, Chunyu Huang4. 1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Department of Cancer Prevention, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China. 2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, Guangdong Province, China. 3. Department of Ophthalmology, Panyu Central Hospital, Guangzhou, 510080, Guangdong Province, China. Electronic address: 23812147@qq.com. 4. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China; Department of Endoscopy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong Province, China. Electronic address: huangchy@sysucc.org.cn.
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.
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.