The role and mechanism of oxidized low-density lipoprotein in the pathogenesis of age-related macular degeneration_Chinese Journal of Ocular Fundus Diseases

Authors：

Wu Tong , Dang Kuanrong , Hui Yannian ,  Du Hongjun

Department of Ophthalmology, Eye Institute of PLA, Xijing Hospital, The Air Force Medical University, Xi’an 710032, China;

Corresponding author：

Du Hongjun, Email: dhj2020@126.com

Keywords：

Macular degeneration; Scavenger receptors, class E; Cell death; Inflammation; Review

DOI：

10.3760/cma.j.cn511434-20200826-00410

Video：

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Abstract Full text Figures/Tables Video References Cited by

Drusen is one of the early hallmark changes of AMD. The oxidative stress and inflammatory reaction caused by oxidative phospholipids (OxPLs) in drusen can lead to retinal pigment epithelium (RPE) cell death (apoptosis, pyroptosis, etc.) and the formation of choroidal neovascularization, which is the pathogenesis of AMD. Pyroptosis, also known as inflammatory necrosis, is one of the main forms of OxPLs induced cell death. Proinflammatory factors released by pyroptic cells can in turn aggravate the inflammatory reaction, leading to further damage. In order to prevent AMD, inflammatory response and cell death may be reduced by regulating lipid metabolism, reducing OxPLs endocytosis and increasing cholesterol efflux. In-depth understanding effects of OxPLs, inflammation and RPE pyrosis in the pathogenesis of AMD in elucidate the pathogenesis of AMD and to seek new treatment measures has important clinical significance.

Citation： Wu Tong, Dang Kuanrong, Hui Yannian, Du Hongjun. The role and mechanism of oxidized low-density lipoprotein in the pathogenesis of age-related macular degeneration. Chinese Journal of Ocular Fundus Diseases, 2021, 37(8): 656-660. doi: 10.3760/cma.j.cn511434-20200826-00410 Copy

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1. Shaw PX, Zhang L, Zhang M, et al. Complement factor H genotypes impact risk of age-related macular degeneration by interaction with oxidized phospholipids[J]. Proc Natl Acad Sci USA, 2012, 109(34): 13757-13762. DOI: 10.1073/pnas.1121309109.
2. 张敏, 李志坚, 王亚敏. 细胞焦亡在眼部疾病中的研究进展[J]. 眼科新进展, 2019, 39(1): 82-85. DOI: 10.13389/j.cnki.rao.2019.2019.Zhang M, Li ZJ, Wang YM. Research progress of pyroptosis in ocular diseases[J]. Rec Adv Ophthalmol, 2019, 39(1): 82-85. DOI: 10.13389/j.cnki.rao.2019.2019.
3. Huang P, Liu W, Chen J, et al. TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3[J]. Cell Biol Int, 2020, 44(11): 2213-2219. DOI: 10.1002/cbin.11429.
4. Chen Y, Bedell M, Zhang K. Age-related macular degeneration: genetic and environmental factors of disease[J]. Mol Interv, 2010, 10(5): 271-281. DOI: 10.1124/mi.10.5.4.
5. Wang L, Clark ME, Crossman DK, et al. Abundant lipid and protein components of drusen[J/OL]. PLoS One, 2010, 5(4): e10329[2010-04-23]. https://pubmed.ncbi.nlm.nih.gov/20428236/. DOI: 10.1371/journal.pone.0010329.
6. Curcio CA, Presley JB, Millican CL, et al. Basal deposits and drusen in eyes with age-related maculopathy: evidence for solid lipid particles[J]. Exp Eye Res, 2005, 80(6): 761-775. DOI: 10.1016/j.exer.2004.09.017.
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11. Strowig T, Henao-Mejia J, Elinav E, et al. Inflammasomes in health and disease[J]. Nature, 2012, 481(7381): 278-286. DOI: 10.1038/nature10759.
12. Sheedy FJ, Grebe A, Rayner KJ, et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation[J]. Nat Immunol, 2013, 14(8): 812-820. DOI: 10.1038/ni.2639.
13. Netea MG, Simon A, Van De Veerdonk F, et al. IL-1beta processing in host defense: beyond the inflammasomes[J/OL]. PLoS Pathog, 2010, 6(2): e1000661[2010-02-26]. https://pubmed.ncbi.nlm.nih.gov/20195505/. DOI: 10.1371/journal.ppat.1000661.
14. Chen L, Yao Q, Xu S, et al. Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux[J]. Biochem Biophys Res Commun, 2018, 495(1): 382-387. DOI: 10.1016/j.bbrc.2017.11.025.
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16. 潘纩, Ismail M.O.Abukhousa, 王艺东新型程序性细胞死亡方式—焦亡的研究进展[J]. 现代生物医学进展, 2019, 19(9): 1793-1797. DOI: 10.13241/j.cnki.pmb.2019.09.043.Pan K, Abukhousa IMO, Wang YD. Research progress of a new type of programmed cell death-pyroptosis[J]. Progress in Modern Biomedicine, 2019, 19(9): 1793-1797. DOI: 10.13241/j.cnki.pmb.2019.09.043.
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18. Zhaolin Z, Jiaojiao C, Peng W, et al. OxLDL induces vascular endothelial cell pyroptosis through miR-125a-5p/TET2 pathway[J]. J Cell Physiol, 2019, 234(5): 7475-7491. DOI: 10.1002/jcp.27509.
19. Zi Y, Yi-An Y, Bing J, et al. Sirt6-induced autophagy restricted TREM-1-mediated pyroptosis in ox-LDL-treated endothelial cells: relevance to prognostication of patients with acute myocardial infarction[J/OL]. Cell Death Discov, 2019, 5: 88[2019-04-12]. https://pubmed.ncbi.nlm.nih.gov/30993014/. DOI: 10.1038/s41420-019-0168-4.
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22. Zeng CY, Li CG, Shu JX, et al. ATP induces caspase-3/gasdermin E-mediated pyroptosis in NLRP3 pathway-blocked murine macrophages[J]. Apoptosis, 2019, 24(9-10): 703-717. DOI: 10.1007/s10495-019-01551-x.
23. Liao Y, Zhang H, He D, et al. Retinal pigment epithelium cell death is associated with NLRP3 inflammasome activation by all-trans retinal[J]. Invest Ophthalmol Vis Sci, 2019, 60(8): 3034-3045. DOI: 10.1167/iovs.18-26360.
24. Datta S, Cano M, Ebrahimi K, et al. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD[J]. Prog Retin Eye Res, 2017, 60: 201-218. DOI: 10.1016/j.preteyeres.2017.03.002.
25. Du H, Xiao X, Stiles T, et al. Novel mechanistic interplay between products of oxidative stress and components of the complement system in AMD pathogenesis[J]. Open J Ophthalmol, 2016, 6(1): 43-50. DOI: 10.4236/ojoph.2016.61006.
26. Kauppinen A, Paterno JJ, Blasiak J, et al. Inflammation and its role in age-related macular degeneration[J]. Cell Mol Life Sci, 2016, 73(9): 1765-1786. DOI: 10.1007/s00018-016-2147-8.
27. Tarallo V, Hirano Y, Gelfand BD, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88[J]. Cell, 2012, 149(4): 847-859. DOI: 10.1016/j.cell.2012.03.036.
28. Gao J, Cui JZ, To E, et al. Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells associated with NLRP3 inflammasome in the rodent eye[J/OL]. J Neuroinflammation, 2018, 15(1): 15[2018-01-12]. https://pubmed.ncbi.nlm.nih.gov/29329580/. DOI: 10.1186/s12974-018-1062-3.
29. Ibrahim J, De Schutter E, Op De Beeck K. GSDME: a potential ally in cancer detection and treatment[J]. Trends in cancer, 2021, 7(5): 392-394. DOI: 10.1016/j.trecan.2020.12.002.
30. Brandstetter C, Patt J, Holz FG, et al. Inflammasome priming increases retinal pigment epithelial cell susceptibility to lipofuscin phototoxicity by changing the cell death mechanism from apoptosis to pyroptosis[J]. J Photochem Photobiol B, 2016, 161: 177-183. DOI: 10.1016/j.jphotobiol.2016.05.018.
31. Kim GY, Lee JW, Ryu HC, et al. Proinflammatory cytokine IL-1beta stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis[J]. J Immunol, 2010, 184(7): 3946-3954. DOI: 10.4049/jimmunol.0901735.
32. Lavalette S, Raoul W, Houssier M, et al. Interleukin-1beta inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration[J]. Am J Pathol, 2011, 178(5): 2416-2423. DOI: 10.1016/j.ajpath.2011.01.013.
33. Li A, Dubey S, Varney ML, et al. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis[J]. J Immunol, 2003, 170(6): 3369-3376. DOI: 10.4049/jimmunol.170.6.3369.
34. Nakao S, Noda K, Zandi S, et al. VAP-1-mediated M2 macrophage infiltration underlies IL-1β-but not VEGF-A-induced lymph-and angiogenesis[J]. Am J Pathol, 2011, 178(4): 1913-1921. DOI: 10.1016/j.ajpath.2011.01.011.
35. Ijima R, Kaneko H, Ye F, et al. Interleukin-18 induces retinal pigment epithelium degeneration in mice[J]. Invest Ophthalmol Vis Sci, 2014, 55(10): 6673-6678. DOI: 10.1167/iovs.14-15367.
36. Wu T, Dang KR, Wang YF, et al. A modified laser-induced choroidal neovascularization animal model with intravitreal oxidized low-density lipoprotein[J]. Int J Ophthalmol, 2020, 13(8): 1187-1194. DOI: 10.18240/ijo.2020.08.03.
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