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other·ophthalmology, retina, preclinical research, biomedical research, endocrinology·PMC10895757

Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy

Diabetology & Metabolic Syndrome · 17 authors, 13 centres

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The study analyzed retinal specimens from Sprague-Dawley rats using single-cell RNA sequencing to investigate cellular changes in early diabetic retinopathy (DR).

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The study analyzed retinal specimens from Sprague-Dawley rats using single-cell RNA sequencing to investigate cellular changes in early diabetic retinopathy (DR). Researchers identified three microglial subtypes: two pro-inflammatory M1 types (Egr2+ M1 and Egr2- M1) and one anti-inflammatory M2 type. They mapped the anatomical locations, dynamic polarization changes, and a possible activation sequence where Egr2- M1 microglia activate earlier than Egr2+ M1 microglia. The work constructed an inflammatory network involving microglia, blood-derived macrophages, and other retinal cells. The findings suggest these novel microglial subtypes and their regulatory networks could be targets for early intervention in DR.

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other

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ophthalmology

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ORIGINAL PAPER

PMC10895757

Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy

Diabetology & Metabolic Syndrome

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ABSTRACT

Background The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. Methods A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. Results We defined three new microglial subtypes at cellular level, including two M1 types ( Egr2 + M1 and Egr2 − M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. Conclusions We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR. Supplementary Information The online version contains supplementary material available at 10.1186/s13098-024-01282-3.

CITATION EXPORT

Yan Wang, Xiongyi Yang, Yuxi Zhang et al.. Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy. Diabetology & Metabolic Syndrome. (2024). https://doi.org/10.1186/s13098-024-01282-3

AUTHORS

17 · 13 CENTRES

Yan Wang, Xiongyi Yang, Yuxi Zhang, Libing Hong, Zhuohang Xie, Wenmin Jiang, Lin Chen, Ke Xiong, Siyu Yang, Meiping Lin, Xi Guo, Qiumo Li, Xiaoqing Deng, Yanhui Lin, Mingzhe Cao, Guoguo Yi, Min Fu

1https://ror.org/01vy4gh70grid.263488.30000 0001 0472 9649Department of Ophthalmology, South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116 People’s Republic of China
2https://ror.org/01vjw4z39grid.284723.80000 0000 8877 7471The Second Clinical School, Southern Medical University, Guangzhou, Guangdong People’s Republic of China
3grid.416466.70000 0004 1757 959XState Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China
4https://ror.org/053v2gh09grid.452708.c0000 0004 1803 0208Department of Ophthalmology, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan People’s Republic of China
5grid.452708.c0000 0004 1803 0208Hunan Clinical Research Center of Ophthalmic Disease, Changsha, 410011 Hunan People’s Republic of China
6https://ror.org/01vjw4z39grid.284723.80000 0000 8877 7471Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, 1333 Xinhu Road, Shenzhen, 518100 Guangdong People’s Republic of China
7grid.416466.70000 0004 1757 959XDepartment of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong People’s Republic of China
8https://ror.org/0064kty71grid.12981.330000 0001 2360 039XDepartment of Ophthalmology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China
9https://ror.org/01vjw4z39grid.284723.80000 0000 8877 7471School of Rehabilitation Medicine, Southern Medical University, Guangzhou, Guangdong People’s Republic of China
10grid.431010.7Health Management Center, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan People’s Republic of China
11https://ror.org/0064kty71grid.12981.330000 0001 2360 039XDepartment of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-Sen University, No. 26, Erheng Road, Yuancun, Tianhe, Guangzhou, Guangdong People’s Republic of China
12https://ror.org/0064kty71grid.12981.330000 0001 2360 039XBiomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
13grid.417404.20000 0004 1771 3058Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong People’s Republic of China