Abstract
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. ARTICLE HIGHLIGHTS: 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.