Single‐cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy

Abstract Diabetic retinopathy (DR) is a leading cause of irreversible blindness in the working‐age populations. Despite decades of research on the pathogenesis of DR for clinical care, a comprehensive understanding of the condition is still lacking due to the intricate cellular diversity and molecular heterogeneity involved. Single‐cell RNA sequencing (scRNA‐seq) has made the high‐throughput molecular profiling of cells across modalities possible which has provided valuable insights into complex biological systems. In this review, we summarise the application of scRNA‐seq in investigating the pathogenesis of DR, focusing on four aspects. These include the identification of differentially expressed genes, characterisation of key cell subpopulations and reconstruction of developmental ‘trajectories’ to unveil their state transition, exploration of complex cell‒cell communication in DR and integration of scRNA‐seq with genome‐wide association studies to identify cell types that are most closely related to DR risk genetic loci. Finally, we discuss the future challenges and expectations associated with studying DR using scRNA‐seq. We anticipate that scRNA‐seq will facilitate the discovery of mechanisms and new treatment targets in the clinical care landscape for patients with DR. Key points Progress in scRNA‐seq for diabetic retinopathy (DR) research includes studies on DR patients, non‐human primates, and the prevalent mouse models. scRNA‐seq facilitates the identification of differentially expressed genes, pivotal cell subpopulations, and complex cell‐cell interactions in DR at single‐cell level. Future scRNA‐seq applications in DR should target specific patient subsets and integrate with single‐cell and spatial multi‐omics approaches.