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Single-Cell Transcriptomics Reveals Dynamic Microglial States and Neural-Immune Networks in Human Diabetic Retinopathy

Yang, L.; Lin, S.; Tao, Y.; Pan, Q.; Cai, T.; Ye, Y.; Liu, J.; Zhou, Y.; Yi, Q.; Lu, Z. H.; Chen, L.; McKay, G.; Rankin, R.; Shao, Y.; Meng, W.

2025-02-08 bioinformatics
10.1101/2025.02.07.637193 bioRxiv
Show abstract

Diabetic retinopathy (DR) is a major cause of vision loss worldwide. Here, we conduct single-cell RNA sequencing of twenty human retina samples (from living and post-mortem donors) across non-diabetic, diabetic, and DR states to create a comprehensive transcriptomic atlas. We identify two stable microglial populations--homeostatic and inflammatory--that exist along a functional continuum, plus a neutrophil cluster within C1QA+ myeloid cells with dynamic transitions occurring throughout disease progression. Module-level analysis reveals divergent transcriptional trajectories: homeostatic microglia maintain energetic programs while selectively upregulating stress elements, whereas inflammatory microglia layer additional pro-inflammatory programs onto preserved biosynthetic foundations. Eleven co-expression modules organize into two major axes: an inflammatory-stress axis, and a regulatory/metabolic-motility axis, with a stable translation module persisting across disease stages. Cell communication analysis further highlights sophisticated neural-immune interactions, particularly between photoreceptors and microglia. Our findings provide insights into the complex cellular dynamics of DR progression and suggest potential therapeutic targets for early intervention.

Published in Genomics · training set

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