miRNA-124 通过抑制小胶质细胞炎症反应预防大鼠糖尿病视网膜病变。
miRNA-124 Prevents Rat Diabetic Retinopathy by Inhibiting the Microglial Inflammatory Response.
机构信息
5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
Department of Vascular Surgery, Medical Faculty Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.
出版信息
Int J Mol Sci. 2023 Jan 24;24(3):2291. doi: 10.3390/ijms24032291.
Diabetic retinopathy (DR) is characterized by vasoregression and glial activation. miRNA-124 (miR-124) reduces retinal microglial activation and alleviates vasoregression in a neurodegenerative rat model. Our aim was to determine whether miR-124 affects vascular and neural damage in the early diabetic retina. Diabetes was induced in 8-week-old rats by streptozotocin (STZ) injection. At 16 and 20 weeks, the diabetic rats were intravitreally injected with miR-124 mimic, and retinae were analyzed at 24 weeks. Microvascular damage was identified by evaluating pericyte loss and acellular capillary (AC) formation. Müller glial activation was assessed by glial fibrillary acidic protein (GFAP) immunofluorescence staining. Microglial activation was determined by immunofluorescent staining of ionized calcium-binding adaptor molecule 1 (Iba1) in whole mount retinae. The neuroretinal function was assessed by electroretinography. The expression of inflammation-associated genes was evaluated by qRT-PCR. A wound healing assay was performed to quantitate the mobility of microglial cells. The results showed that miR-124 treatment alleviated diabetic vasoregression by reducing AC formation and pericyte loss. miR-124 blunted Müller glial- and microglial activation in diabetic retinae and ameliorated neuroretinal function. The retinal expression of inflammatory factors including , , , , , , , , and was reduced by miR-124 administration. The elevated mobility of microglia upon high glucose exposure was normalized by miR-124. The expression of the transcription factor PU.1 and lipid raft protein Flot1 was downregulated by miR-124. In rat DR, miR-124 prevents vasoregression and glial activation, improves neuroretinal function, and modulates microglial activation and inflammatory responses.
糖尿病性视网膜病变（DR）的特征是血管退化和神经胶质细胞激活。miRNA-124（miR-124）可减少神经退行性大鼠模型中视网膜小胶质细胞的激活，并减轻血管退化。我们的目的是确定 miR-124 是否会影响早期糖尿病视网膜中的血管和神经损伤。通过链脲佐菌素（STZ）注射诱导 8 周龄大鼠发生糖尿病。在 16 和 20 周时，用 miR-124 模拟物对糖尿病大鼠进行玻璃体内注射，并在 24 周时分析视网膜。通过评估周细胞丧失和无细胞毛细血管（AC）形成来鉴定微血管损伤。通过胶质纤维酸性蛋白（GFAP）免疫荧光染色评估神经胶质细胞激活。通过全视网膜免疫荧光染色离子钙结合衔接分子 1（Iba1）来确定小胶质细胞激活。通过视网膜电图评估神经视网膜功能。通过 qRT-PCR 评估炎症相关基因的表达。通过划痕愈合试验定量测定小胶质细胞的迁移能力。结果表明，miR-124 通过减少 AC 形成和周细胞丧失来减轻糖尿病血管退化。miR-124 减弱了糖尿病视网膜中 Müller 胶质细胞和小胶质细胞的激活，并改善了神经视网膜功能。miR-124 给药可降低视网膜中炎症因子（包括 、 、 、 、 、 、 、 和 ）的表达。miR-124 可使高葡萄糖暴露后小胶质细胞的迁移能力正常化。miR-124 下调转录因子 PU.1 和脂筏蛋白 Flot1 的表达。在大鼠 DR 中，miR-124 可预防血管退化和神经胶质细胞激活，改善神经视网膜功能，并调节小胶质细胞激活和炎症反应。
Zotero 插件