Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (5): 93-99.doi: 10.6040/j.issn.1673-3770.0.2021.203

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Progress in diabetic retinopathy mechanisms and cellular models

WANG Jiaojiao, LI MiaoOverview,SONG ZongmingGuidance   

  1. Department of Ophthalmology, Henan Provincial People's Hospital/Henan Eye Hospital/Henan Eye Institute, Zhengzhou 450003, Henan, China
  • Published:2022-09-20

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Abstract: Diabetic retinopathy is the leading cause of poor vision and blindness in adults. A reasonable model for diabetic retinopathy can not only simulate its pathogenic mechanism, but also reduce economic investment. Therefore, screening and constructing suitable cell models is the core of research. In this paper, the mechanisms of inflammatory response, apoptosis, vascular dysfunction, and neurovascular unit dysfunction in diabetic retinopathy were discussed. Moreover, several models of endothelial cells, pericytes, retinal pigment epithelial cells, and glial cells were summarized to provide a useful reference for further studies on the mechanism of diabetic retinopathy and the development of relevant drugs.

Key words: Diabetic retinopathy, Vitro model, Construct, Mechanism, Progress

CLC Number: 

  • R774
[1] Zhao K, Liu J, Dong G, et al. Preliminary research on the effects and mechanisms of umbilical cord derived mesenchymal stem cells in streptozotocin induced diabetic retinopathy[J]. Int J Mol Med, 2020, 46(2): 849-858. doi:10.3892/ijmm.2020.4623.
[2] Xiao F, Li L, Fu JS, et al. Regulation of the miR-19b-mediated SOCS6-JAK2/STAT3 pathway by lncRNA MEG3 is involved in high glucose-induced apoptosis in hRMECs[J]. Biosci Rep, 2020, 40(7): BSR20194370. doi:10.1042/BSR20194370.
[3] 刘志高, 王淑雅, 韩旭光, 等. 增殖性糖尿病视网膜病变术前玻璃体腔应用阿柏西普的时机及其疗效观察[J]. 山东大学耳鼻喉眼学报, 2021,35(1): 99-103. doi: 10.6040/j.issn.1673-3770.0.2020.250. LIU Zhigao, WANG Shuya, HAN Xuguang, et al. Preoperative timing and the effect of intravitreal aflibercept injection for proliferative diabetic retinopathy patients[J]. J Otolaryngol Ophthalmol Shandong Univ, 2021, 35(1): 99-103. doi: 10.6040/j.issn.1673-3770.0.2020.250.
[4] Fehér J, Taurone S, Spoletini M, et al. Ultrastructure of neurovascular changes in human diabetic retinopathy[J]. Int J Immunopathol Pharmacol, 2018, 31: 394632017748841. doi:10.1177/0394632017748841.
[5] Figueira J, Fletcher E, Massin P, et al. Ranibizumab plus panretinal photocoagulation versus panretinal photocoagulation alone for high-risk proliferative diabetic retinopathy(PROTEUS study)[J]. Ophthalmology, 2018, 125(5): 691-700. doi:10.1016/j.ophtha.2017.12.008.
[6] Kinuthia UM, Wolf A, Langmann T. Microglia and inflammatory responses in diabetic retinopathy[J]. Front Immunol, 2020, 11: 564077. doi:10.3389/fimmu.2020.564077.
[7] McKinsey GL, Lizama CO, Keown-Lang AE, et al. A new genetic strategy for targeting microglia in development and disease[J]. Elife, 2020, 9: e54590. doi:10.7554/eLife.54590.
[8] Abe N, Choudhury ME, Watanabe M, et al. Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: a study using a hypnotic bromovalerylurea[J]. Glia, 2018, 66(10): 2158-2173. doi:10.1002/glia.23469.
[9] Greter M, Lelios I, Croxford AL. Microglia versus myeloid cell nomenclature during brain inflammation[J]. Front Immunol, 2015, 6: 249. doi:10.3389/fimmu.2015.00249.
[10] Calado SM, Alves LS, Simão S, et al. GLUT1 activity contributes to the impairment of PEDF secretion by the RPE[J]. Mol Vis, 2016, 22: 761-770.
[11] Kim DI, Park MJ, Choi JH, et al. Hyperglycemia-induced GLP-1R downregulation causes RPE cell apoptosis[J]. Int J Biochem Cell Biol, 2015, 59: 41-51. doi:10.1016/j.biocel.2014.11.018.
[12] Su XJ, Sorenson CM, Sheibani N. Isolation and characterization of murine retinal endothelial cells[J]. Mol Vis, 2003, 9: 171-178. doi: 10.1002/mrd.10265.
[13] Bhattacharya S, Khan MM, Ghosh C, et al. The role of Dermcidin isoform-2 in the occurrence and severity of Diabetes[J]. Sci Rep, 2017, 7(1): 8252. doi:10.1038/s41598-017-07958-3.
[14] Song Y, Tian X, Wang XH, et al. Vascular protection of salicin on IL-1β-induced endothelial inflammatory response and damages in retinal endothelial cells[J]. Artif Cells Nanomed Biotechnol, 2019, 47(1): 1995-2002. doi:10.1080/21691401.2019.1608220.
[15] Gogg S, Smith U, Jansson PA. Increased MAPK activation and impaired insulin signaling in subcutaneous microvascular endothelial cells in type 2 diabetes: the role of endothelin-1[J]. Diabetes, 2009, 58(10): 2238-2245. doi:10.2337/db08-0961.
[16] Roberts AC, Gohil J, Hudson L, et al. Aberrant phenotype in human endothelial cells of diabetic origin: implications for saphenous vein graft failure?[J]. J Diabetes Res, 2015, 2015: 409432. doi:10.1155/2015/409432.
[17] Liu JT, Chen SL, Biswas S, et al. Glucose-induced oxidative stress and accelerated aging in endothelial cells are mediated by the depletion of mitochondrial SIRTs[J]. Physiol Rep, 2020, 8(3): e14331. doi:10.14814/phy2.14331.
[18] Boscaro C, Trenti A, Baggio C, et al. Sex differences in the pro-angiogenic response of human endothelial cells: focus on PFKFB3 and FAK activation[J]. Front Pharmacol, 2020, 11: 587221. doi:10.3389/fphar.2020.587221.
[19] Midena E, Micera A, Frizziero L, et al. Sub-threshold micropulse laser treatment reduces inflammatory biomarkers in aqueous humour of diabetic patients with macular edema[J]. Sci Rep, 2019, 9(1): 10034. doi:10.1038/s41598-019-46515-y.
[20] Yumnamcha T, Guerra M, Singh LP, et al. Metabolic dysregulation and neurovascular dysfunction in diabetic retinopathy[J]. Antioxidants(Basel), 2020, 9(12): E1244. doi:10.3390/antiox9121244.
[21] Tu YY, Song E, Wang ZZ, et al. Melatonin attenuates oxidative stress and inflammation of Müller cells in diabetic retinopathy via activating the Sirt1 pathway[J]. Biomedecine Pharmacother, 2021, 137: 111274. doi:10.1016/j.biopha.2021.111274.
[22] Capozzi ME, Giblin MJ, Penn JS. Palmitic acid induces Müller cell inflammation that is potentiated by Co-treatment with glucose[J]. Sci Rep, 2018, 8(1): 5459. doi:10.1038/s41598-018-23601-1.
[23] Guo YW, Hong WM, Wang XM, et al. MicroRNAs in microglia: how do MicroRNAs affect activation, inflammation, polarization of microglia and mediate the interaction between microglia and glioma?[J]. Front Mol Neurosci, 2019, 12: 125. doi:10.3389/fnmol.2019.00125.
[24] 易秋雪. 外源性EPO通过调节小胶质细胞保护糖尿病视网膜病变血-视网膜内屏障[D]. 上海: 上海交通大学, 2019.
[25] Mesquida M, Drawnel F, Fauser S. The role of inflammation in diabetic eye disease[J]. Semin Immunopathol, 2019, 41(4): 427-445. doi:10.1007/s00281-019-00750-7.
[26] Shao K, Xi L, Cang Z, et al. Knockdown of NEAT1 exerts suppressive effects on diabetic retinopathy progression via inactivating TGF-β1 and VEGF signaling pathways[J]. J Cell Physiol, 2020, 235(12): 9361-9369. doi:10.1002/jcp.29740.
[27] Hammer SS, Beli E, Kady N, et al. The mechanism of diabetic retinopathy pathogenesis unifying key lipid regulators, sirtuin 1 and liver X receptor[J]. EBioMedicine, 2017, 22: 181-190. doi:10.1016/j.ebiom.2017.07.008.
[28] Yumnamcha T, Devi TS, Singh LP. Auranofin mediates mitochondrial dysregulation and inflammatory cell death in human retinal pigment epithelial cells: implications of retinal neurodegenerative diseases[J]. Front Neurosci, 2019, 13: 1065. doi:10.3389/fnins.2019.01065.
[29] Becker S, Carroll LS, Vinberg F. Diabetic photoreceptors: Mechanisms underlying changes in structure and function[J]. Vis Neurosci, 2020, 37: E008. doi:10.1017/s0952523820000097.
[30] Gao M, Liu HY, Xiao YS, et al. xCT regulates redox homeostasis and promotes photoreceptor survival after retinal detachment[J]. Free Radic Biol Med, 2020, 158: 32-43. doi:10.1016/j.freeradbiomed.2020.06.023.
[31] Lai TT, Yang CM, Yang CH. Astaxanthin protects retinal photoreceptor cells against high glucose-induced oxidative stress by induction of antioxidant enzymes via the PI3K/Akt/Nrf2 pathway[J]. Antioxidants(Basel), 2020, 9(8): E729. doi:10.3390/antiox9080729.
[32] Lv J, Bao SY, Liu TH, et al. Sulforaphane delays diabetes-induced retinal photoreceptor cell degeneration[J]. Cell Tissue Res, 2020, 382(3): 477-486. doi:10.1007/s00441-020-03267-w.
[33] Leal EC, Aveleira CA, Castilho AF, et al. High glucose and oxidative/nitrosative stress conditions induce apoptosis in retinal endothelial cells by a caspase-independent pathway[J]. Exp Eye Res, 2009, 88(5): 983-991. doi:10.1016/j.exer.2008.12.010.
[34] Cai X, McGinnis JF. Diabetic retinopathy: animal models, therapies, and perspectives[J]. J Diabetes Res, 2016, 2016: 3789217. doi:10.1155/2016/3789217.
[35] Suarez S, McCollum GW, Jayagopal A, et al. High glucose-induced retinal pericyte apoptosis depends on association of GAPDH and Siah1[J]. J Biol Chem, 2015, 290(47): 28311-28320. doi:10.1074/jbc.m115.682385.
[36] Shi H, Koronyo Y, Fuchs DT, et al. Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease[J]. Acta Neuropathol Commun, 2020, 8(1): 202. doi:10.1186/s40478-020-01076-4.
[37] Fu DX, Yu JY, Connell AR, et al. Beneficial effects of berberine on oxidized LDL-induced cytotoxicity to human retinal Müller cells[J]. Invest Ophthalmol Vis Sci, 2016, 57(7): 3369-3379. doi:10.1167/iovs.16-19291.
[38] 李蓉, 姚杨, 杜军辉, 等. 自噬在高糖条件下视网膜色素上皮细胞表达血管内皮生长因子促进RF/6A细胞血管生成中的作用[J]. 眼科新进展, 2019,39(8): 714-718. doi:10.13389/j.cnki.rao.2019.0163. LI Rong, YAO Yang, DU Junhui, et al. Autophagy promotes angiogenesis of RF/6A cells following upregulating the expression of vascular endothelial growth factor in retinal pigment epithelial cells under high glucose conditions[J]. Recent Adv Ophthalmol, 2019, 39(8): 714-718. doi:10.13389/j.cnki.rao.2019.0163.
[39] Hu J, Li T, Du X, et al. G protein-coupled receptor 91 signaling in diabetic retinopathy and hypoxic retinal diseases[J]. Vision Res, 2017, 139: 59-64. doi:10.1016/j.visres.2017.05.001.
[40] Chen M, Liu B, Ma J, et al. Protective effect of mitochondria-targeted peptide MTP-131 against oxidative stress-induced apoptosis in RGC-5 cells[J]. Mol Med Rep, 2017, 15(4): 2179-2185. doi:10.3892/mmr.2017.6271.
[41] López-Contreras AK, Martínez-Ruiz MG, Olvera-Montaño C, et al. Importance of the use of oxidative stress biomarkers and inflammatory profile in aqueous and vitreous humor in diabetic retinopathy[J]. Antioxidants, 2020, 9(9): 891. doi:10.3390/antiox9090891.
[42] Shosha E, Xu ZM, Narayanan S, et al. Mechanisms of diabetes-induced endothelial cell senescence: role of arginase 1[J]. Int J Mol Sci, 2018, 19(4): 1215. doi:10.3390/ijms19041215.
[43] Kady N, Yan Y, Salazar T, et al. Increase in acid sphingomyelinase level in human retinal endothelial cells and CD34+ circulating angiogenic cells isolated from diabetic individuals is associated with dysfunctional retinal vasculature and vascular repair process in diabetes[J]. J Clin Lipidol, 2017, 11(3): 694-703. doi:10.1016/j.jacl.2017.03.007.
[44] 李红梅, 雷霍, 杨晓春, 等. 天麻素对高糖培养的小胶质细胞和视网膜神经节细胞相互作用的影响[J]. 昆明理工大学学报(自然科学版), 2015, 40(6): 96-102. doi:10.16112/j.cnki.53-1223/n.2015.06.016. LI Hongmei, LEI Huo, YANG Xiaochun, et al. Effect of gastrodin on interactions between microglia and retinal ganglion cells cultured by high glucose[J]. J Kunming Univ Sci Technol Nat Sci Ed, 2015, 40(6): 96-102. doi:10.16112/j.cnki.53-1223/n.2015.06.016.
[45] Durham JT, Dulmovits BM, Cronk SM, et al. Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy?[J]. Invest Ophthalmol Vis Sci, 2015, 56(6): 3441-3459. doi:10.1167/iovs.14-13945.
[46] 廖宇洁, 于晓彦, 金轶平, 等. 体外共培养模式下小胶质细胞影响内皮细胞紧密连接[J]. 海南医学, 2019, 30(5): 548-551. doi: 10.3969/j.issn.1003-6350.2019.05.002. LIAO Yujie, YU Xiaoyan, JIN Yiping, et al. Effect of microglia on the expression of tight junction in human umbilical vein endothelial cells by co-culture in vitro[J]. Hainan Med J, 2019, 30(5): 548-551. doi: 10.3969/j.issn.1003-6350.2019.05.002.
[47] 张晓梅, 王彬杰, 王巍, 等. Transwell小室共培养条件下缺氧时视网膜色素上皮细胞对内皮细胞增殖的影响[J]. 哈尔滨医科大学学报, 2011, 45(4): 312-315. doi: 10.3969/j.issn.1000-1905.2011.04.005. ZHANG Xiaomei, WANG Binjie, WANG Wei, et al. Effects of retinal pigment epithelium cells on proliferation of endothelial cells under hypoxia in a co-culture system[J]. J Harbin Med Univ, 2011, 45(4): 312-315. doi: 10.3969/j.issn.1000-1905.2011.04.005.
[48] 袁晨, 张梅, 谢学军. 血-视网膜内屏障体外模型构建研究进展[J]. 国际眼科杂志, 2021,21(6): 991-995. doi: 10.3980/j.issn.1672-5123.2021.6.10. YUAN Chen, ZHANG Mei, XIE Xuejun. Progress in the construction of inner blood retinal barrier model in vitro[J]. Int Eye Sci, 2021, 21(6): 991-995. doi: 10.3980/j.issn.1672-5123.2021.6.10.
[49] 李红, 樊映川. 视网膜神经血管相互作用机制及其在糖尿病视网膜病变中的病理改变的研究进展[J]. 实用医院临床杂志, 2015, 12(3): 148-150. doi: 10.3969/j.issn.1672-6170.2015.03.057. LI Hong, FAN Yingchuan. Neurovascular interactions in the retina: mechanism and the advances of pathological changes of diabetic retinopathy[J]. Pract J Clin Med, 2015, 12(3): 148-150. doi: 10.3969/j.issn.1672-6170.2015.03.057.
[50] Garhöfer G, Chua J, Tan BY, et al. Retinal neurovascular coupling in diabetes[J]. J Clin Med, 2020, 9(9): E2829. doi:10.3390/jcm9092829.
[51] Shahulhameed S, Swain S, Jana S, et al. A robust model system for retinal hypoxia: live imaging of calcium dynamics and gene expression studies in primary human mixed retinal culture[J]. Front Neurosci, 2019, 13: 1445. doi:10.3389/fnins.2019.01445.
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