Protection against light‐induced retinal degeneration via dual anti‐inflammatory and anti‐angiogenic functions of thrombospondin‐1

作者：Yahan Ju, Zhimin Tang, Xiaochan Dai, Huiqin Gao, Jing Zhang, Jing Zhang, Yan Liu, Yanan Yang, Ni Ni, Dandan Zhang, Yuyao Wang, Luqiao Yin, Luqiao Yin, Min Luo, Jianhua Zhang, Jianhua Zhang, Ping Gu · 发表于：British Journal of Pharmacology · 年份：2020 · DOI：10.1111/bph.15303 · 被引用次数：32 · 研究领域：Angiogenesis and VEGF in Cancer、Retinal Diseases and Treatments、Laser Applications in Dentistry and Medicine

BACKGROUND AND PURPOSE: Retinal photodamage is a high-risk factor for age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide. However, both the pathogenesis and effective therapies for retinal photodamage are still unclear and debated. EXPERIMENTAL APPROACH: The anti-inflammatory effects of thrombospondin-1 on blue light-induced inflammation in ARPE-19 cells and in retinal inflammation were evaluated. Furthermore, the anti-angiogenic effects of thrombospondin-1 on human microvascular endothelial cells (hMEC-1 cells) and a laser-induced choroidal neovascularisation (CNV) mouse model were evaluated. in vitro experiments, including western blotting, immunocytochemistry, migration assays and tube formation assays, as well as in vivo experiments, including immunofluorescence, visual electrophysiology, spectral-domain optical coherence tomography, and fluorescein angiography, were employed to evaluate the anti-inflammatory and anti-angiogenic effects of thrombospondin-1. KEY RESULTS: Specific effects of blue light-induced retinal inflammation and pathological angiogenesis were reflected by up-regulation of pro-inflammatory factors and activation of angiogenic responses, predominantly regulated by the NF-κB and VEGFR2 pathways respectively. During the blue light-induced pathological progress, THBS-1 derived from retinal pigment epithelium down-regulated proteomics and biological assays. Thrombospondin-1 treatment also suppressed inflammatory in...