Research progress of polyunsaturated fatty acids in inflammation of diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Liu Xiaoxin , Liu Xinyi ,  Liu Kun

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;

Corresponding author：

Liu Kun, Email: drliukun@sjtu.edu.cn

Keywords：

Diabetic retinopathy; Metabolomics; Inflammation; Polyunsaturated fatty acid; Review

DOI：

10.3760/cma.j.cn511434-20240730-00290

Video：

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Abstract Full text Figures/Tables Video References Cited by

Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), and its pathogenesis remains incompletely understood. Research has identified inflammation as a key factor in the onset and progression of DR. As a group of systemic metabolic disorders, the dysregulation of polyunsaturated fatty acid (PUFA) metabolism induced by DM is closely related to the inflammatory mechanisms in DR. Recent metabolomic studies have revealed that in various stages of DR and in diabetic animal models, most upregulated PUFAs and their derivatives act as pro-inflammatory mediators, while downregulated PUFAs and their derivatives are predominantly anti-inflammatory. In the progression of DR, some PUFAs may exert anti-inflammatory effects by inhibiting microglial activation, reducing the expression of inflammatory proteins, antagonizing the pro-inflammatory effects of arachidonic acid, and suppressing the activation of inflammasomes and the migration of neutrophils. Conversely, other PUFAs may promote inflammation through mechanisms such as the formation of pro-inflammatory mediators resembling prostaglandins, facilitating leukocyte adhesion, and inducing oxidative stress responses. PUFAs play a complex dual role in the inflammatory mechanisms of DR. A deeper understanding of these mechanisms not only aids in elucidating the pathogenesis of DR but also provides potential targets for developing new therapeutic strategies.

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1. 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.
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4. Wishart DS. Emerging applications of metabolomics in drug discovery and precision medicine[J]. Nat Rev Drug Discov, 2016, 15(7): 473-484. DOI: 10.1038/nrd.2016.32.
5. Joussen AM, Poulaki V, Le ML, et al. A central role for inflammation in the pathogenesis of diabetic retinopathy[J]. FASEB J, 2004, 18(12): 1450-1452. DOI: 10.1096/fj.03-1476fje.
6. Ahsan H. Diabetic retinopathy--biomolecules and multiple pathophysiology[J]. Diabetes Metab Syndr, 2015, 9(1): 51-54. DOI: 10.1016/j.dsx.2014.09.011.
7. Van Hove I, Hu TT, Beets K, et al. Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration[J/OL]. Prog Retin Eye Res, 2021, 85: 100966[2021-03-26]. https://pubmed.ncbi.nlm.nih.gov/33775825/. DOI: 10.1016/j.preteyeres.2021.100966.
8. Zeng HY, Green WR, Tso MO. Microglial activation in human diabetic retinopathy[J]. Arch Ophthalmol, 2008, 126(2): 227-232. DOI: 10.1001/archophthalmol.2007.65.
9. Ibrahim AS, El-Remessy AB, Matragoon S, et al. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes[J]. Diabetes, 2011, 60(4): 1122-1133. DOI: 10.2337/db10-1160.
10. Xu H, Chen M. Diabetic retinopathy and dysregulated innate immunity[J]. Vision Res, 2017, 139: 39-46. DOI: 10.1016/j.visres.2017.04.013.
11. Nagayach A, Patro N, Patro I. Astrocytic and microglial response in experimentally induced diabetic rat brain[J]. Metab Brain Dis, 2014, 29(3): 747-761. DOI: 10.1007/s11011-014-9562-z.
12. Dietzen NM, Arcario MJ, Chen LJ, et al. Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites[J/OL]. Elife, 2022, 11: e74306[2022-01-04]. https://pubmed.ncbi.nlm.nih.gov/34982031/. DOI: 10.7554/eLife.74306.
13. Bloch W, Diel P, Zacher J. Ion channel regulation in endothelial function: the key role of dietary polyunsaturated fatty acids for TRPV4 activity[J]. Cardiovasc Res, 2021, 117(12): 2409-2410. DOI: 10.1093/cvr/cvab097.
14. Liput KP, Lepczyński A, Ogłuszka M, et al. Effects of dietary n-3 and n-6 polyunsaturated fatty acids in inflammation and cancerogenesis[J/OL]. Int J Mol Sci, 2021, 22(13): 6965[2021-01-28]. https://pubmed.ncbi.nlm.nih.gov/34203461/. DOI: 10.3390/ijms22136965.
15. Wang Z, Tang J, Jin E, et al. Metabolomic comparison followed by cross-validation of enzyme-linked immunosorbent assay to reveal potential biomarkers of diabetic retinopathy in chinese with type 2 diabetes[J/OL]. Front Endocrinol (Lausanne), 2022, 13: 986303[2022-09-08]. https://pubmed.ncbi.nlm.nih.gov/36157454/. DOI: 10.3389/fendo.2022.986303.
16. Wang Z, Tang J, Jin E, et al. Serum untargeted metabolomics reveal potential biomarkers of progression of diabetic retinopathy in asians[J/OL]. Front Mol Biosci, 2022, 9: 871291[2022-01-09]. https://pubmed.ncbi.nlm.nih.gov/35755823/. DOI: 10.3389/fmolb.2022.871291.
17. Guo C, Jiang D, Xu Y, et al. High-coverage serum metabolomics reveals metabolic pathway dysregulation in diabetic retinopathy: a propensity score-matched study[J/OL]. Front Mol Biosci, 2022, 9: 822647[2022-03-17]. https://pubmed.ncbi.nlm.nih.gov/35372500/. DOI: 10.3389/fmolb.2022.822647.
18. Alkhalaf A, Kleefstra N, Groenier KH, et al. Effect of benfotiamine on advanced glycation endproducts and markers of endothelial dysfunction and inflammation in diabetic nephropathy[J/OL]. PLoS One, 2012, 7(7): e40427[2012-07-06]. https://pubmed.ncbi.nlm.nih.gov/22792314/. DOI: 10.1371/journal.pone.0040427.
19. Abdelrahman AA, Bunch KL, Sandow PV, et al. Systemic administration of pegylated arginase-1 attenuates the progression of diabetic retinopathy[J/OL]. Cells, 2022, 11(18): 2890[2022-09-16]. https://pubmed.ncbi.nlm.nih.gov/36139465/. DOI: 10.3390/cells11182890.
20. Zhao T, Wang Y, Guo X, et al. Altered oxylipin levels in human vitreous indicate imbalance in pro-/anti-inflammatory homeostasis in proliferative diabetic retinopathy[J/OL]. Exp Eye Res, 2022, 214: 108799[2021-10-21]. https://pubmed.ncbi.nlm.nih.gov/34687725/. DOI: 10.1016/j.exer.2021.108799.
21. Chu KO, Chan TI, Chan KP, et al. Untargeted metabolomic analysis of aqueous humor in diabetic macular edema[J]. Mol Vis, 2022, 28: 230-244.
22. Wen X, Ng TK, Liu Q, et al. Azelaic acid and guanosine in tears improve discrimination of proliferative from non-proliferative diabetic retinopathy in type-2 diabetes patients: a tear metabolomics study[J/OL]. Heliyon, 2023, 9(5): e16109[2023-05-18]. https://pubmed.ncbi.nlm.nih.gov/37305454/. DOI: 10.1016/j.heliyon.2023.e16109.
23. Zhou Z, Zheng Z, Xiong X, et al. Gut microbiota composition and fecal metabolic profiling in patients with diabetic retinopathy[J/OL]. Front Cell Dev Biol, 2021, 9: 732204[2021-10-15]. https://pubmed.ncbi.nlm.nih.gov/34722512/. DOI: 10.3389/fcell.2021.732204.
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