Wang Yan, Yang Xiongyi, Zhang Yuxi, Hong Libing, Xie Zhuohang, Jiang Wenmin, Chen Lin, Xiong Ke, Yang Siyu, Lin Meiping, Guo Xi, Li Qiumo, Deng Xiaoqing, Lin Yanhui, Cao Mingzhe, Yi Guoguo, Fu Min
Department of Ophthalmology, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, People's Republic of China.
The Second Clinical School, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Diabetol Metab Syndr. 2024 Feb 26;16(1):49. doi: 10.1186/s13098-024-01282-3.
The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing.
A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology.
We defined three new microglial subtypes at cellular level, including two M1 types (Egr2 M1 and Egr2 M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR.
We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.
糖尿病视网膜病变（DR）是一种致盲性疾病，其病理生理机制错综复杂。DR曾被认为是一种微血管疾病。然而，越来越多的研究表明，视网膜小胶质细胞诱导的炎症先于微血管病变出现。炎症激活过程中，小胶质细胞M1/M2极化模式的二元概念一直存在争议。在本研究中，我们通过单细胞RNA测序证实小胶质细胞在早期DR中变化最为显著。
从供体SD大鼠收集了总共五个视网膜标本。使用单细胞测序技术分析DR早期视网膜各种细胞的变化。
我们在细胞水平定义了三种新的小胶质细胞亚型，包括两种M1型（Egr2 M1和Egr2 M1）和一种M2型。我们还揭示了这些亚型之间的解剖位置、极化表型的动态变化以及不同细胞可能的激活顺序和相互激活调节机制。此外，我们构建了一个涉及小胶质细胞、血源性巨噬细胞和其他视网膜非神经元细胞的炎症网络。针对新的疾病特异性小胶质细胞亚型进行靶向研究可以缩短药物筛选和临床应用的时间，这为早期控制和逆转DR提供了思路。
我们发现小胶质细胞在早期DR中表现出最明显的差异表达变化，并在单细胞水平揭示了高糖微环境中小胶质细胞的变化。我们的综合分析将有助于实现早期逆转并控制DR的发生和发展。
