Unlike in the healthy mammalian retina, macrophages in retinal degenerative states are not solely comprised of microglia but may include monocyte-derived recruits. Recent studies have applied transgenics, lineage-tracing, and transcriptomics to help decipher the distinct roles of these two cell types in the diseasesettings of inherited retinal degenerations and age-related macular degeneration.Literature discussed here focuses on the ectopic presence of both macrophage types in the extracellular site surrounding the outer aspect ofphotoreceptor cells (i.e.,the subretinal space), which is crucially involved in the pathobiology. From these studies we propose a working model in which perturbed photoreceptor states cause microglial dominant migration to the subretinal space as a protective response, whereas the abundant presence ofmonocyte-derived cells there instead drives and accelerates pathology. The latter, we propose, is underpinned by specific genetic and nongenetic determinants that lead to a maladaptive macrophage state.

中文翻译：

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小胶质细胞与单核细胞：在视网膜退行性疾病中的不同作用

与健康的哺乳动物视网膜不同，视网膜退化状态的巨噬细胞不仅由小胶质细胞组成，还可能包括单核细胞衍生的新兵。最近的研究应用转基因学、谱系追踪和转录组学来帮助破译这两种细胞类型在遗传性视网膜变性和年龄相关性黄斑变性的疾病背景中的不同作用。 这里讨论的文献重点关注两种巨噬细胞类型的异位存在围绕光感受器细胞外部的细胞外位点（即视网膜下空间），其在病理生物学中至关重要。从这些研究中，我们提出了一个工作模型，其中扰动的光感受器状态导致小胶质细胞显性迁移到视网膜下空间作为保护反应，而那里大量存在的单核细胞衍生细胞反而会推动和加速病理。我们建议，后者由导致巨噬细胞适应不良状态的特定遗传和非遗传决定因素支持。