Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, People's Republic of China.
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
BMJ Open Diabetes Res Care. 2024 Jul 16;12(4):e004189. doi: 10.1136/bmjdrc-2024-004189.
Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR.
We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects.
Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein () gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells.
This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.
糖尿病视网膜病变（DR）是糖尿病常见的血管并发症，也是全球视力丧失的主要原因。在 DR 的发病机制中观察到内皮细胞（EC）异质性。阐明调控 EC 异质性的潜在机制可能为 DR 的 EC 特异性治疗提供新的思路。
我们使用来自基因表达综合数据库的单细胞数据，探索糖尿病视网膜与非糖尿病视网膜之间的 EC 异质性，并鉴定可能与 DR 相关的潜在基因。通过 CCK-8 检测、EdU 检测、Transwell 检测和管形成检测，确定鉴定基因在血管生成效应中的作用。
我们的分析在视网膜中鉴定出三种不同的 EC 亚群，并表明线粒体定位的谷氨酸丰富蛋白（Mitochondria-localized glutamic acid-rich protein，MGARP）基因可能参与 DR 的发病机制。沉默 Mgarp 显著抑制了视网膜内皮细胞的增殖、迁移和管形成能力。
本研究不仅为视网膜 EC 转录组异质性和病理改变提供了新的见解，而且有望通过靶向 EC 特异性基因为抗血管生成治疗铺平道路。
