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.

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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.
2. Li YN, Liang HW, Zhang CL, et al. Ophthalmic solution of smart supramolecular peptides to capture semaphorin 4D against diabetic retinopathy[J/OL]. Adv Sci (Weinh), 2023, 10(3): e2203351[2022-11-27]. https://pubmed.ncbi.nlm.nih.gov/36437109/. DOI: 10.1002/advs.202203351.
3. 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): eaay5356[2020-08-21]. https://pubmed.ncbi.nlm.nih.gov/32820093/. DOI: 10.1126/science.aay5356.
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.
5. Tan JL, Yi J, Cao XY, et al. Celastrol: The new dawn in the treatment of vascular remodeling diseases[J/OL]. Biomed Pharmacother, 2023, 158: 114177[2023-02-01]. https://pubmed.ncbi.nlm.nih.gov/36809293/. DOI: 10.1016/j.biopha.2022.114177.
6. Deng H, Eichmann A, Schwartz MA. Fluid shear stress-regulated vascular remodeling: past, present, and future[J]. Arterioscler Thromb Vasc Biol, 2025, 45(6): 882-900. DOI: 10.1161/ATVBAHA.125.322557.
7. 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.
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.
9. Rajesh A, Droho S, Lavine JA. Macrophages in close proximity to the vitreoretinal interface are potential biomarkers of inflammation during retinal vascular disease[J/OL]. J Neuroinflammation, 2022, 19(1): 203[2022-08-08]. https://pubmed.ncbi.nlm.nih.gov/35941655/. DOI: 10.1186/s12974-022-02562-3.
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.
12. Garrido-Trigo A, Corraliza AM, Veny M, et al. Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease[J/OL]. Nat Commun, 2023, 14(1): 4506[2023-07-26]. https://pubmed.ncbi.nlm.nih.gov/37495570/. DOI: 10.1038/s41467-023-40156-6.
13. Kerneur C, Cano CE, Olive D. Major pathways involved in macrophage polarization in cancer[J/OL]. Front Immunol, 2022, 13: 1026954[2022-10-17]. https://pubmed.ncbi.nlm.nih.gov/36325334/. DOI: 10.3389/fimmu.2022.1026954.
14. He X, Li Z, Li S, et al. Huoxue Tongluo tablet enhances atherosclerosis efferocytosis by promoting the differentiation of Trem2+ macrophages via PPARγ signaling pathway[J/OL]. Phytomedicine, 2025, 140: 156579[2025-05-01]. https://pubmed.ncbi.nlm.nih.gov/40068297/. DOI: 10.1016/j.phymed.2025.156579.
15. King EM, Zhao Y, Moore CM, et al. Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung[J/OL]. JCI Insight, 2024, 9(24): e182700[2024-12-20]. https://pubmed.ncbi.nlm.nih.gov/39509324/. DOI: 10.1172/jci.insight.182700.
16. Zhong X, Zhang F, Xiao H, et al. Single-cell transcriptome analysis of macrophage subpopulations contributing to chemotherapy resistance in ovarian cancer[J/OL]. Immunobiology, 2024, 229(5): 152811[2024-05-18]. https://pubmed.ncbi.nlm.nih.gov/38941863/. DOI: 10.1016/j.imbio.2024.152811.
17. Kovoor E, Chauhan SK, Hajrasouliha A. Role of inflammatory cells in pathophysiology and management of diabetic retinopathy[J]. Surv Ophthalmol, 2022, 67(6): 1563-1573. DOI: 10.1016/j.survophthal.2022.07.008.
18. Saadane A, Veenstra AA, Minns MS, et al. CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice[J]. Diabetologia, 2023, 66(3): 590-602. DOI: 10.1007/s00125-022-05860-w.
19. Gong X, Zhao Q, Zhang H, et al. The effects of mesenchymal stem cells-derived exosomes on metabolic reprogramming in scar formation and wound healing[J]. Int J Nanomedicine, 2024, 19: 9871-9887. DOI: 10.2147/IJN.S480901.
20. Russo S, Kwiatkowski M, Govorukhina N, et al. Meta-inflammation and metabolic reprogramming of macrophages in diabetes and obesity: the importance of metabolites[J/OL]. Front Immunol, 2021, 12: 746151[2021-11-05]. https://pubmed.ncbi.nlm.nih.gov/34804028/. DOI: 10.3389/fimmu.2021.746151.
21. Florance I, Ramasubbu S. Current understanding on the role of lipids in macrophages and associated diseases[J/OL]. Int J Mol Sci, 2022, 24(1): 589[2022-12-29]. https://pubmed.ncbi.nlm.nih.gov/36614031/. DOI: 10.3390/ijms24010589.
22. Li J, Zou P, Xiao R, et al. Indole-3-propionic acid alleviates DSS-induced colitis in mice through macrophage glycolipid metabolism[J/OL]. Int Immunopharmacol, 2025, 152: 114388[2025-04-16]. https://pubmed.ncbi.nlm.nih.gov/40086057/. DOI: 10.1016/j.intimp.2025.114388.
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.
24. Wang X, Xie Z, Zhang J, et al. Interaction between lipid metabolism and macrophage polarization in atherosclerosis[J/OL]. iScience, 2025, 28(4): 112168[2025-04-18]. https://pubmed.ncbi.nlm.nih.gov/40201117/. DOI: 10.1016/j.isci.2025.112168.
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.
30. Ju C, Liu R, Ma Y, et al. Single-cell analysis combined with transcriptome sequencing identifies autophagy hub genes in macrophages after spinal cord injury[J/OL]. Clin Immunol, 2024, 270: 110412[2024-11-28]. https://pubmed.ncbi.nlm.nih.gov/39612968/. DOI: 10.1016/j.clim.2024.110412.
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.
32. Chen F, Wang N, Liao J, et al. Esculetin rebalances M1/M2 macrophage polarization to treat sepsis-induced acute lung injury through regulating metabolic reprogramming[J/OL]. J Cell Mol Med, 2024, 28(21): e70178[2024-11-13]. https://pubmed.ncbi.nlm.nih.gov/39535339/. DOI: 10.1111/jcmm.70178.
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Chinese Journal of Ocular Fundus Diseases

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

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