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

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 remain unclear and controversial. EXPERIMENTAL APPROACHES The anti-inflammatory effects of thrombospondin-1 (THBS-1) on blue-light-induced ARPE-19 cellular inflammation and retinal inflammation were evaluated. Furthermore, the anti-angiogenic effects of THBS-1 on human microvascular endothelium cell line (hMEC-1 cells) and a laser-induced choroidal neovascularization (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 THBS-1. KEY RESULTS The specific effects of blue-light-induced retinal inflammation and pathological angiogenesis were reflected by an upregulation of pro-inflammatory factors and an activation of angiogenic responses, which were dominantly regulated by the NF-κB and VEGFR2 pathways, respectively. During the blue-light-induced pathological progress, RPE-derived THBS-1 was found to be significantly downregulated in proteomics and biological analyses. Interestingly, THBS-1 treatment effectively suppressed inflammatory infiltration and neovascular leakage, and the superior protective effect of THBS-1 was additionally demonstrated by a substantial rescue of visual function. Mechanically, THBS-1 was found to be capable of reversing blue-light-induced retinal inflammation and angiogenesis by blocking the activated NF-κB and VEGFR2 pathways, respectively. CONCLUSION AND IMPLICATIONS This study revealed that THBS-1, with dual anti-inflammatory and anti-neovascularization properties, is a promising agent for protection against blue-light-induced retinal damage and retinal degenerative disorders that are pathologically associated with inflammatory and angiogenic progress.