Deng Boxiong, Nnebe Chelsea, Prakhar Praveen, Ren Xiaobai, Sun Duo, Sun Yue, Wang Sui
Department of Ophthalmology, Mary M. and Sash A. Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA.
Diabetes. 2025 Oct 1;74(10):1720-1726. doi: 10.2337/dbi24-0009.
Diabetes triggers cell-type-specific responses in the retina, leading to vascular lesions, glial dysfunction, and neurodegeneration, all of which contribute to the progression of diabetic retinopathy (DR). However, the specific cell types involved in disease development and the molecular mechanisms driving their responses have not yet been fully clarified, impeding the creation of effective therapeutic strategies. Recent advancements in single-cell or single-nuclei transcriptomic technologies have provided a systematic approach to profile transcript-level alterations at single-cell resolution, allowing for an in-depth analysis of diabetes-induced retinal transcriptional changes across various animal models for DR. Here, in the context of research funded by the American Diabetes Association Pathway to Stop Diabetes program, we discuss the cell-type-specific responses in the neural retina identified through single-cell transcriptomic analyses. We emphasize new insights into neural retinal responses, potential therapeutic targets, and the limitations and unresolved topics that warrant further investigation. This article is part of a series of perspectives that report on research funded by the American Diabetes Association Pathway to Stop Diabetes program.
Single-cell transcriptomics provides a powerful solution for dissecting diabetes-induced cell-type-specific responses in mammalian retina. This article summarizes key findings from recent single-cell transcriptomic studies regarding the mechanisms of diabetic retinopathy, with a particular emphasis on the neural retina. Specific retinal neuronal types/subtypes exhibit heightened sensitivity to diabetes at the transcriptional level. Retinal Müller glial cells are key contributors to diabetic retinopathy and promising therapeutic targets for retinal protection against diabetes.
糖尿病会引发视网膜中特定细胞类型的反应，导致血管病变、神经胶质细胞功能障碍和神经退行性变，所有这些都促使糖尿病视网膜病变（DR）的进展。然而，疾病发展过程中涉及的具体细胞类型以及驱动其反应的分子机制尚未完全阐明，这阻碍了有效治疗策略的制定。单细胞或单细胞核转录组技术的最新进展提供了一种系统方法，可在单细胞分辨率下描绘转录水平的变化，从而深入分析糖尿病在各种糖尿病视网膜病变动物模型中引起的视网膜转录变化。在此，在美国糖尿病协会“阻止糖尿病之路”项目资助的研究背景下，我们讨论通过单细胞转录组分析确定的神经视网膜中特定细胞类型的反应。我们强调对神经视网膜反应的新见解、潜在的治疗靶点以及有待进一步研究的局限性和未解决的问题。本文是由美国糖尿病协会“阻止糖尿病之路”项目资助的一系列观点报道的一部分。
单细胞转录组学为剖析糖尿病在哺乳动物视网膜中引发的特定细胞类型反应提供了有力的解决方案。本文总结了近期单细胞转录组研究关于糖尿病视网膜病变机制的关键发现，特别关注神经视网膜。特定的视网膜神经元类型/亚型在转录水平上对糖尿病表现出更高的敏感性。视网膜穆勒神经胶质细胞是糖尿病视网膜病变的关键促成因素，也是视网膜抵御糖尿病的有前景的治疗靶点。
