Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany.
Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, 50931 Cologne, Germany.
Int J Mol Sci. 2020 Apr 13;21(8):2689. doi: 10.3390/ijms21082689.
Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.
脉络膜新生血管（CNV）是一种病理过程，其中异常血管侵入哺乳动物眼睛的视网膜下空间。它是普遍的新生血管性年龄相关性黄斑变性（nAMD）的特征。循环 microRNAs（cmiRNAs）被认为是各种与年龄相关的疾病（包括 nAMD）的潜在有价值的生物标志物。在这里，我们在已建立的激光诱导的 CNV 小鼠模型中研究了 cmiRNA 的表达。在 C57Bl/6 小鼠中诱导 CNV 后，通过 RNA 下一代测序最初全局确定了血液衍生的 cmiRNAs，并且通过定量逆转录 PCR（RT-qPCR）在血液、视网膜和视网膜色素上皮（RPE）/脉络膜组织中独立复制了最强烈失调的 cmiRNAs。我们的研究结果表明，两种 microRNAs，mmu-mir-486a-5p 和 mmur-mir-92a-3p，在 CNV 形成过程中始终失调。此外，在功能体外测定中，观察到 mmu-mir-486a-5p 和 mmu-mir-92a-3p 对小鼠小胶质细胞活力有显著影响，而 mmu-mir-92a-3p 也对小胶质细胞迁移有影响。总之，我们报告了在小鼠激光诱导的 CNV 病变起始后，血液和 RPE/脉络膜中两种 miRNAs 的稳健失调，突出了它们在 CNV 相关并发症的病理和最终治疗中的潜在作用。
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