Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
Am J Pathol. 2013 Mar;182(3):875-85. doi: 10.1016/j.ajpath.2012.11.031. Epub 2013 Jan 10.
Microglial cells are the resident macrophages of the central nervous system and participate in both innate and adaptive immune responses but can also lead to exacerbation of neurodegenerative pathologies after viral infections. Microglia in the outer layers of the retina and the subretinal space are thought to be involved in retinal diseases where low-grade chronic inflammation and oxidative stress play a role. This study investigated the effect of systemic infection with murine cytomegalovirus on the distribution and dynamics of retinal microglia cells. Systemic infection with murine cytomegalovirus elicited a significant increase in the number of microglia in the subretinal space and an accumulation of iris macrophages, along with morphological signs of activation. Interferon γ (IFN-γ)-deficient mice failed to induce changes in microglia distribution. Bone marrow chimera experiments confirmed that microglial cells in the subretinal space were not recruited from the circulating monocyte pool, but rather represented an accumulation of resident microglial cells from within the retina. Our results demonstrate that a systemic viral infection can lead to IFN-γ-mediated accumulation of microglia into the outer retinal layers and offer proof of concept that systemic viral infections alter the ocular microenvironment and therefore, may influence the course of diseases such as macular degeneration, diabetic retinopathy, or autoimmune uveitis, where low-grade inflammation is implicated.
小胶质细胞是中枢神经系统的固有巨噬细胞，参与固有和适应性免疫反应，但在病毒感染后也可能导致神经退行性病变的恶化。视网膜外层和视网膜下空间的小胶质细胞被认为与视网膜疾病有关，在这些疾病中，低水平的慢性炎症和氧化应激起着作用。本研究调查了系统性感染鼠巨细胞病毒对视网膜小胶质细胞分布和动态的影响。系统性感染鼠巨细胞病毒会导致视网膜下空间中小胶质细胞数量显著增加，并伴有虹膜巨噬细胞的积累，以及形态激活的迹象。干扰素 γ（IFN-γ）缺陷小鼠未能诱导小胶质细胞分布的变化。骨髓嵌合体实验证实，视网膜下空间中的小胶质细胞不是从循环单核细胞池中募集而来的，而是代表来自视网膜内的固有小胶质细胞的积累。我们的研究结果表明，系统性病毒感染可导致 IFN-γ介导的小胶质细胞向视网膜外层的积累，并提供了概念验证，即系统性病毒感染改变了眼部微环境，因此可能影响黄斑变性、糖尿病性视网膜病变或自身免疫性葡萄膜炎等疾病的病程，这些疾病都与低度炎症有关。
