Progress in single-cell sequencing of retinal vein occlusion or ischemic hypoxic retinopathy

Abstract

Retinal vein occlusion (RVO) and ischemic hypoxic retinopathy (IHR) are leading cause of irreversible vision loss worldwide, compelled by complex microvascular dysfunction, neuroinflammation, and tissue hypoxia. Despite advances in imaging and treatment, a comprehensive understanding of cellular and molecular heterogeneity underlying these pathologies remains limited. Recently, single-cell RNA sequencing (scRNA-seq) has emerged as a transformative technology, enabling unprecedented resolution of cellular dynamics, transcriptomic landscapes, and intracellular communication within the retina. Single-cell technologies continue to evolve, they are poised to revolutionize our understanding of retinal vascular diseases, ultimately paving the way for precision diagnostics and targeted interventions. This technique has revolutionized our understanding regarding complex biological systems and enables proper analysis of cellular heterogeneity. This review highlights the recent progress for the application SCS to dissect the pathophysiology of RVO and IHR. Moreover, current study summarizes findings on altered gene expression endothelial cells, Muller glia, micro glia and photoreceptors under ischemic and hypoxic stress, shedding light on potential therapeutic targets and biomarkers. Furthermore, this study explores the integration of snRNA-seq, spatial transcriptomics, and multi-omics approaches to enhance the spatial and temporal mapping of retinal responses. Additionally, discuss the current challenges, including sample preservation, retinal cell-type annotation, and cross-species translation, while offering insights into future directions such as personalized medicine and regenerative strategies. This paper aims to provide clinicians and researchers with a comprehensive update on the rapidly expanding frontier of single-cell analysis in retinal ischemic diseases.