Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune response in retinal vascular diseases such as age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Here, we set out to elucidate the dynamics of the immune response during progression and regression of pathological neovascularization in retinopathy. In a mouse model of oxygen-induced retinopathy, we report that dexamethasone, a broad-spectrum corticosteroid, suppresses initial formation of pathological preretinal neovascularization in early stages of disease, yet blunts reparative inflammation by impairing distinct myeloid cell populations, and hence reduces beneficial vascular remodeling in later stages of disease. Using genetic depletion of distinct components of the innate immune response, we demonstrate that CX3C chemokine receptor 1-expressing microglia contribute to angiogenesis. Conversely, myeloid cells expressing lysozyme 2 are recruited to sites of damaged blood vessels and pathological neovascularization where they partake in a reparative process that ultimately restores circulatory homeostasis to the retina. Hence, the Janus-faced properties of anti-inflammatory drugs should be considered, particularly in stages associated with persistent neovascularization.

中文翻译：

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皮质类固醇可减少病理性血管生成，但损害视网膜病变模型中的修复性血管重塑


组织炎症通常与细胞损伤广泛相关，但无菌性炎症在有益的组织重塑中也起着关键作用。在中枢神经系统中，这是通过视网膜血管疾病（如年龄相关性黄斑变性、糖尿病性视网膜病变和早产儿视网膜病变）中主要先天免疫反应观察到的。在这里，我们着手阐明视网膜病变病理性新生血管形成进展和消退过程中免疫反应的动力学。在氧诱导的视网膜病变小鼠模型中，我们报道了地塞米松（一种广谱皮质类固醇）在疾病早期抑制病理性视网膜前新生血管形成的初始形成，但通过损害不同的髓系细胞群来减弱修复性炎症，从而减少疾病后期的有益血管重塑。利用先天免疫反应不同成分的遗传耗竭，我们证明表达 CX3C 趋化因子受体 1 的小胶质细胞有助于血管生成。相反，表达溶菌酶 2 的髓系细胞被募集到血管受损和病理新生血管形成的部位，在那里它们参与修复过程，最终恢复视网膜的循环稳态。因此，应考虑抗炎药的 Janus 面特性，尤其是在与持续新生血管形成相关的阶段。