Research progress on macrophage lipid metabolism reprogramming in the regulation of vascular remodeling in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Wu Xinyang ¹ , Mao Xiying ¹ , Cao Qiuchen ¹ , Pu Lijun ² ,  Liu Qinghuai ¹

1. Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;
2. Department of Ophthalmology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou 215600, China;

Corresponding?author：

Liu Qinghuai, Email: liuqh@njmu.edu.cn

Keywords：

Macrophage; Lipid metabolism; Metabolic reprogramming; Vascular remodeling; Diabetic retinopathy; Review

DOI：

10.3760/cma.j.cn511434-20250306-00092

Video：

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Abstract Full text Figures/Tables Video References Cited by

As essential immune cells for retinal homeostasis and repair, macrophages play a pivotal role throughout vascular remodeling, a central pathological feature of diabetic retinopathy (DR). Emerging evidence indicates that macrophages actively adapt to the diabetic microenvironment through metabolic reprogramming. Notably, lipid metabolic reprogramming plays a crucial role in shaping macrophage activation phenotypes, modulating immune functions, and regulating the synthesis of inflammatory mediators, thereby influencing vascular remodeling. A deeper understanding of lipid metabolic reprogramming in macrophage-mediated vascular remodeling may provide novel immunometabolic targets for therapeutic intervention in DR.

Citation： Wu Xinyang, Mao Xiying, Cao Qiuchen, Pu Lijun, Liu Qinghuai. Research progress on macrophage lipid metabolism reprogramming in the regulation of vascular remodeling in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2026, 42(1): 85-91. doi: 10.3760/cma.j.cn511434-20250306-00092 Copy

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1. Hou X, Wang L, Zhu D, et al. Prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy in adults with diabetes in China[J/OL]. Nat Commun, 2023, 14(1): 4296[2023-07-18]. https://pubmed.ncbi.nlm.nih.gov/37463878/. DOI: 10.1038/s41467-023-39864-w.
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4. Yamaguchi M, Nakao S, Arima M, et al. Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation[J]. Diabetologia, 2024, 67(10): 2329-2345. DOI: 10.1007/s00125-024-06215-3.
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8. Blot G, Karadayi R, Przegralek L, et al. Perilipin 2-positive mononuclear phagocytes accumulate in the diabetic retina and promote PPARγ-dependent vasodegeneration[J/OL]. J Clin Invest, 2023, 133(19): e161348[2023-10-05]. https://pubmed.ncbi.nlm.nih.gov/37781924/. DOI: 10.1172/JCI161348.
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10. Mills SA, Jobling AI, Dixon MA, et al. Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy[J/OL]. Proc Natl Acad Sci USA, 2021, 118(51): e2112561118[2021-12-21]. https://pubmed.ncbi.nlm.nih.gov/34903661/. DOI: 10.1073/pnas.2112561118.
11. Heieis GA, Patente TA, Almeida L, et al. Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection[J/OL]. Nat Commun, 2023, 14(1): 5627[2023-09-12]. https://pubmed.ncbi.nlm.nih.gov/37699869/. DOI: 10.1038/s41467-023-41353-z.
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23. Sun R, Lei C, Xu Z, et al. Neutral ceramidase regulates breast cancer progression by metabolic programming of TREM2-associated macrophages[J/OL]. Nat Commun, 2024, 15(1): 966[2024-02-01]. https://pubmed.ncbi.nlm.nih.gov/38302493/. DOI: 10.1038/s41467-024-45084-7.
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25. Vassiliou E, Farias-Pereira R. Impact of lipid metabolism on macrophage polarization: implications for inflammation and tumor immunity[J/OL]. Int J Mol Sci, 2023, 24(15): 12032[2023-07-27]. https://pubmed.ncbi.nlm.nih.gov/37569407/. DOI: 10.3390/ijms241512032.
26. Liu X, Lu J, Ni X, et al. FASN promotes lipid metabolism and progression in colorectal cancer via the SP1/PLA2G4B axis[J/OL]. Cell Death Discov, 2025, 11(1): 122[2025-03-28]. https://pubmed.ncbi.nlm.nih.gov/40148316/. DOI: 10.1038/s41420-025-02409-9.
27. Brailey PM, Evans L, López-Rodríguez JC, et al. CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses[J/OL]. Nat Commun, 2022, 13(1): 6723[2022-11-07]. https://pubmed.ncbi.nlm.nih.gov/36344546/. DOI: 10.1038/s41467-022-34532-x.
28. Zuo S, Wang Y, Bao H, et al. Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair[J/OL]. Nat Commun, 2024, 15(1): 7269[2024-08-23]. https://pubmed.ncbi.nlm.nih.gov/39179603/. DOI: 10.1038/s41467-024-51736-5.
29. Zhou T, Yan K, Zhang Y, et al. Fenofibrate suppresses corneal neovascularization by regulating lipid metabolism through PPARα signaling pathway[J/OL]. Front Pharmacol, 2022, 13: 1000254[2022-12-16]. https://pubmed.ncbi.nlm.nih.gov/36588740/. DOI: 10.3389/fphar.2022.1000254.
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31. Faraj TA, Edroos G, Erridge C. Toll-like receptor stimulants in processed meats promote lipid accumulation in macrophages and atherosclerosis in apoe-/- mice[J/OL]. Food Chem Toxicol, 2024, 186: 114539[2024-02-21]. https://pubmed.ncbi.nlm.nih.gov/38387521/. DOI: 10.1016/j.fct.2024.114539.
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Current status and future prospects of community-based diabetic retinopathy screening in China

Chinese Journal of Ocular Fundus Diseases

Research progress on macrophage lipid metabolism reprogramming in the regulation of vascular remodeling in diabetic retinopathy

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