The choroid, which provides vascular supply to the outer retina, demonstrates progressive degeneration in aging and age-related macular degeneration (AMD). However mechanisms that maintain or compromise choroidal homeostasis are obscure. We discovered that the ablation of choroidal macrophages via CSF1R blockade was associated with choroidal vascular atrophy and retinal pigment epithelial (RPE) changes including structural disruption, downregulation of visual cycle genes, and altered angiogenic factor expression. Suspending CSF1R blockade following ablation enabled spontaneous macrophage regeneration, which fully restored original macrophage distributions and morphologies. Macrophage regeneration was accompanied by arrested vascular degeneration and ameliorated pathological RPE alterations. These findings suggest that choroidal macrophages play a previously unappreciated trophic role in maintaining choroidal vasculature and RPE cells, implicating insufficiency in choroidal macrophage function as a factor in aging- and AMD-associated pathology. Modulating macrophage function may constitute a strategy for the therapeutic preservation of the choroid and RPE in age-related retinal disorders.

中文翻译：

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CSF1R阻滞诱导巨噬细胞消融并导致小鼠脉络膜血管萎缩和RPE紊乱

脉络膜向外部视网膜提供血管供应，显示出衰老和与年龄相关的黄斑变性（AMD）的进行性变性。然而，维持或损害脉络膜稳态的机制尚不清楚。我们发现通过CSF1R阻断消融脉络膜巨噬细胞与脉络膜血管萎缩和视网膜色素上皮（RPE）改变有关，包括结构破坏，视觉循环基因下调和血管生成因子表达改变。消融后暂停CSF1R阻断使自发巨噬细胞再生，从而完全恢复了原始巨噬细胞的分布和形态。巨噬细胞再生伴随着停滞的血管变性和改善的病理RPE改变。这些发现表明脉络膜巨噬细胞在维持脉络膜脉管系统和RPE细胞方面起着以前未被认识的营养作用，暗示脉络膜巨噬细胞功能不足是衰老和AMD相关病理的一个因素。调节巨噬细胞功能可能构成在年龄相关性视网膜疾病中治疗性保存脉络膜和RPE的策略。