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

Abstract

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 infiltration and neovascular leakage. The protective effect of Thrombospondin‐1 was additionally demonstrated by a substantial rescue of visual function. Mechanistically, thrombospondin‐1 reversed blue light‐induced retinal inflammation and angiogenesis by blocking the activated NF‐κB and VEGFR2 pathways, respectively. Conclusion and Implications Thrombospondin‐1, with dual anti‐inflammatory and anti‐neovascularisation properties, is a promising agent for protection against blue light‐induced retinal damage and retinal degenerative disorders which are pathologically associated with inflammatory and angiogenic progress. LINKED ARTICLES This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc

Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases

“…The laser-induced CNV mouse model was generated according to a previously established method [ 30 ]. Male C57BL/6J mice (6–8 weeks old, 20–25 g) were used to generate the CNV model.…”

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

“…In addition, numerous non-classical pro-angiogenic signals and auxiliary molecules have been identified, such as erythropoietin (EPO) [14], apelin [15], coagulation factor XIII (FXIII) [16], pro-inflammatory cytokines [17][18][19][20][21][22][23], or exosomes [24][25][26][27]. Anti-angiogenic factors, on the other hand, such as thrombospondin-1 [28], endostatin [29], tumstatin [30], interferon-α (IFN-α) [31], or IFN-β [32] limit the angiogenesis by maintaining the quiescent state of endothelial cells. The balance between pro-and anti-angiogenic factors is crucial for normal, functional vessel formation; therefore, its deregulation results in pathology and contributes to the progression of diseases, such as cancer.…”

Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition

“…Live/Dead and CCK-8 Analysis: According to a previously conducted study, CCK-8 and live/dead kits were used to evaluate cell survival and death. [26] RPE cells were plated in 24-well plates and 96-well plates to analyze live/dead staining and CCK-8 assays, respectively. At the indicated times, the optical density at 450 nm (O.D.…”

“…Mice were anesthetized with isoflurane/oxygen (induction: 3% at 1.0 L min −1 ; maintenance: 1.5% at 0.6 L min −1 ; Suzhou kunchen Biotechnology Co., Ltd). [26] Then, mice eyes were dilated under red light. After that, the mouse tail and forehead were fitted with ground electrodes and reference electrodes, respectively, and the cornea was placed with a pair of 3 mm gold loop electrodes to record the responses of rods and cones to light stimulus using an Espion E3 machine (Diagnosys, MA).…”