Single-cell RNA sequencing-based research progress analysis of microglia in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Xu Fangcheng ,  Wu Haixiang

1. Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China;

Corresponding author：

Wu Haixiang, Email: whx577@163.com

Keywords：

Microglia; Diabetic retinopathy; Heterogeneity; Single-cell RNA sequencing; Review

DOI：

10.3760/cma.j.cn511434-20230703-00287

Video：

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Diabetic retinopathy (DR) is one of the main causes of vision loss and irreversible blindness in the working-age population, closely regarded as the destruction of the retinal neurovascular unit (NVU). As an important component of the NVU, retinal microglia (RMG) plays a vital role in the progression of DR. In recent years, single-cell RNA sequencing (scRNA-seq) technology has emerged as an important tool in transcriptomic analysis. This latest method reveals the heterogeneity and complexity of RNA transcriptional profiles within individual cells, as well as the composition of different cell types and functions. Utilizing scRNA-seq technology, researchers have further revealed the role of RMG in the occurrence and development of DR, discovering phenotypic heterogeneity, regional heterogeneity, and cell-to-cell communication in RMG. It is anticipated that in the future, more omics technologies and multi-omics correlation analysis methods will be applied to DR and even other ophthalmic diseases, exploring potential diagnostic and therapeutic targets, providing different perspectives for the clinical diagnosis, treatment, and scientific research of DR, and truly promoting clinical translation through technological innovation, thereby benefiting patients with DR diseases.

Citation： Xu Fangcheng, Wu Haixiang. Single-cell RNA sequencing-based research progress analysis of microglia in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2024, 40(2): 165-169. doi: 10.3760/cma.j.cn511434-20230703-00287 Copy

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1. Sivaprasad S, Sen S, Cunha-Vaz J. Perspectives of diabetic retinopathy-challenges and opportunities[J]. Eye (Lond), 2023, 37(11): 2183-2191. DOI: 10.1038/s41433-022-02335-5.
2. 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2022年)-基于循证医学修订[J]. 中华眼底病杂志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Pathology Group of Ophthalmology Branch of Chinese Medical Association, Fundus Pathology Group of Ophthalmology Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)[J]. Chin J Ophthalmol, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.
3. Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J/OL]. Diabetes Res Clin Pract, 2022, 183: 109119[2021-12-06]. https://pubmed.ncbi.nlm.nih.gov/34879977/. DOI: 10.1016/j.diabres.2021.109119.
4. Teo ZL, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis[J]. Ophthalmology, 2021, 128(11): 1580-1591. DOI: 10.1016/j.ophtha.2021.04.027.
5. Fletcher EL, Dixon MA, Mills SA, et al. Anomalies in neurovascular coupling during early diabetes: a review[J]. Clin Exp Ophthalmol, 2023, 51(1): 81-91. DOI: 10.1111/ceo.14190.
6. Vargas-Soria M, García-Alloza M, Corraliza-Gómez M. Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies[J]. J Neuroinflammation, 2023, 20(1): 57. DOI: 10.1186/s12974-023-02740-x.
7. Yi W, Lu Y, Zhong S, et al. A single-cell transcriptome atlas of the aging human and macaque retina[J]. Nati Sci Rev, 2020, 8(4): 179. DOI: 10.1093/nsr/nwaa179.
8. Yip SH, Sham PC, Wang J. Evaluation of tools for highly variable gene discovery from single-cell RNA-seq data[J]. Brief Bioinform, 2019, 20(4): 1583-1589. DOI: 10.1093/bib/bby011.
9. Jovic D, Liang X, Zeng H, et al. Single-cell RNA sequencing technologies and applications: a brief overview[J/OL]. Clin Transl Med, 2022, 12(3): e694[2022-03-01]. https://pubmed.ncbi.nlm.nih.gov/35352511/. DOI: 10.1002/ctm2.694.
10. Mao P, Shen Y, Mao X, et al. The single-cell landscape of alternative transcription start sites of diabetic retina[J/OL]. Exp Eye Res, 2023, 233: 109520[2023-05-24]. https://pubmed.ncbi.nlm.nih.gov/37236522/. DOI: 10.1016/j.exer.2023.109520.
11. Macosko EZ, Basu A, Satija R, et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets[J]. Cell, 2015, 161(5): 1202-1214. DOI: 10.1016/j.cell.2015.05.002.
12. Lukowski SW, Lo CY, Sharov AA, et al. A single-cell transcriptome atlas of the adult human retina[J/OL]. EMBO J, 2019, 38(18): e100811[2019-09-16]. https://pubmed.ncbi.nlm.nih.gov/31436334/. DOI: 10.15252/embj.2018100811.
13. Voigt AP, Whitmore SS, Flamme-Wiese MJ, et al. Molecular characterization of foveal versus peripheral human retina by single-cell RNA sequencing[J]. Exp Eye Res, 2019, 184: 234-242. DOI: 10.1016/j.exer.2019.05.001.
14. Zhang R, Huang C, Chen Y, et al. Single-cell transcriptomic analysis revealing changes in retinal cell subpopulation levels and the pathways involved in diabetic retinopathy[J]. Ann Transl Med, 2022, 10(10): 562. DOI: 10.21037/atm-22-1546.
15. Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter?[J]. Diabetologia, 2018, 61(9): 1902-1912. DOI: 10.1007/s00125-018-4692-1.
16. 易秋雪, 张敬法, 柳林. 小胶质细胞在糖尿病视网膜病变中的作用[J]. 国际眼科杂志, 2019, 19(12): 2048-2052. DOI: 10.3980/j.issn.1672-5123.2019.12.11.Yi QX, Zhang JF, Liu L. Function of microglia in diabetic retinopathy[J]. Int Eye Sci, 2019, 19(12): 2048-2052. DOI: 10.3980/j.issn.1672-5123.2019.12.11.
17. Anderson SR, Roberts JM, Ghena N, et al. Neuronal apoptosis drives remodeling states of microglia and shifts in survival pathway dependence[J/OL]. eLife, 2022, 11: e76564[2022-04-28]. https://pubmed.ncbi.nlm.nih.gov/35481836/. DOI: 10.7554/eLife.76564.
18. Lv K, Ying H, Hu G, et al. Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy[J/OL]. Front Immunol, 2022, 13: 942768[2022-09-02]. https://pubmed.ncbi.nlm.nih.gov/36119084/. DOI: 10.3389/fimmu.2022.942768.
19. Hu Z, Mao X, Chen M, et al. Single-cell transcriptomics reveals novel role of microglia in fibrovascular membrane of proliferative diabetic retinopathy[J]. Diabetes, 2022, 71(4): 762-773. DOI: 10.2337/db21-0551.
20. Binet F, Cagnone G, Crespo-Garcia S, et al. Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy[J/OL]. Science, 2020, 369(6506): e5356[2020-08-21]. https://pubmed.ncbi.nlm.nih.gov/32820093/. DOI: 10.1126/science.aay5356.
21. Liu Z, Shi H, Xu J, et al. Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy[J/OL]. JCI Insight, 2022, 7(23): e160940[2022-12-08]. https://pubmed.ncbi.nlm.nih.gov/36264636/. DOI: 10.1172/jci.insight.160940.
22. Van Hove I, De Groef L, Boeckx B, et al. Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy[J]. Diabetologia, 2020, 63(10): 2235-2248. DOI: 10.1007/s00125-020-05218-0.
23. Paolicelli RC, Sierra A, Stevens B, et al. Microglia states and nomenclature: a field at its crossroads[J]. Neuron, 2022, 110(21): 3458-3483. DOI: 10.1016/j.neuron.2022.10.020.
24. Fu X, Feng S, Qin H, et al. Microglia: the breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy[J/OL]. Front Mol Neurosci, 2023, 16: 1100254[2023-01-23]. https://pubmed.ncbi.nlm.nih.gov/36756614/. DOI: 10.3389/fnmol.2023.1100254.
25. Yamaguchi M, Nakao S, Wada I, et al. Identifying hyperreflective foci in diabetic retinopathy via VEGF-induced local self-renewal of CX3CR1+ vitreous resident macrophages[J]. Diabetes, 2022, 71(12): 2685-2701. DOI: 10.2337/db21-0247.
26. Kinuthia UM, Wolf A, Langmann T. Microglia and inflammatory responses in diabetic retinopathy[J/OL]. Front Immunol, 2020, 11: 564077[2020-11-06]. https://pubmed.ncbi.nlm.nih.gov/33240260/. DOI: 10.3389/fimmu.2020.564077.
27. Wu J, Zhang C, Yang Q, et al. Imaging hyperreflective foci as an inflammatory biomarker after anti-VEGF treatment in neovascular age-related macular degeneration patients with optical coherence tomography angiography[J/OL]. BioMed Res Int, 2021, 2021: 6648191[2021-02-03]. https://pubmed.ncbi.nlm.nih.gov/33614783/. DOI: 10.1155/2021/6648191.
28. Kodjikian L, Bellocq D, Bandello F, et al. First-line treatment algorithm and guidelines in center-involving diabetic macular edema[J]. Eur J Ophthalmol, 2019, 29(6): 573-584. DOI: 10.1177/1120672119857511.
29. Qin HF, Shi FJ, Zhang CY, et al. Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion[J]. Int J ophthalmol, 2022, 15(8): 1296-1304. DOI: 10.18240/ijo.2022.08.11.
30. Rathnasamy G, Foulds WS, Ling EA, et al. Retinal microglia-a key player in healthy and diseased retina[J]. Prog Neurobiol, 2019, 173: 18-40. DOI: 10.1016/j.pneurobio.2018.05.006.
31. Silverman SM, Wong WT. Microglia in the retina: roles in development, maturity, and disease[J]. Annu Rev Vis Sci, 2018, 4: 45-77. DOI: 10.1146/annurev-vision-091517-034425.
32. Frizziero L, Midena G, Longhin E, et al. Early retinal changes by OCT angiography and multifocal electroretinography in diabetes[J/OL]. J Clin Med, 2020, 9(11): 3514[2020-10-30]. https://pubmed.ncbi.nlm.nih.gov/33143008/. DOI: 10.3390/jcm9113514.
33. Uddin MI, Kilburn TC, Duvall CL, et al. Visualizing HIF-1α mRNA in a subpopulation of bone marrow-derived cells to predict retinal neovascularization[J]. ACS Chem Biol, 2020, 15(11): 3004-3012. DOI: 10.1021/acschembio.0c00662.
34. Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy[J]. Nat Rev Endocrinol, 2021, 17(4): 195-206. DOI: 10.1038/s41574-020-00451-4.
35. Solomon SD, Chew E, Duh EJ, et al. Diabetic retinopathy: a position statement by the American diabetes association[J]. Diabetes Care, 2017, 40(3): 412-418. DOI: 10.2337/dc16-2641.
36. Nian S, Lo ACY, Mi Y, et al. Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets[J]. Eye Vis (Lond), 2021, 8(1): 15. DOI: 10.1186/s40662-021-00239-1.
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Chinese Journal of Ocular Fundus Diseases

Single-cell RNA sequencing-based research progress analysis of microglia in diabetic retinopathy

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