Protective effects of melatonin on endothelial cells and pericytes in diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Sun Dandan ,  Xu Xun

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China;

Corresponding author：

Xu Xun, Email: drxuxun@tom.com

Keywords：

Melatonin; Diabetic retinopathy; Endothelial cells; Pericytes; Review

DOI：

10.3760/cma.j.cn511434-20190321-00106

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Intravitreal injection of anti-VEGF drugs has gradually become the first-line treatment for diabetic retinopathy (DR). However, diabetic macular edema (DME) caused by DR blood-retinal barrier damage is less sensitive to anti-VEGF drugs.Therefore, it is necessary to find supplementary drugs or alternative drugs that can effectively protect the structure of the blood vessel wall. Melatonin is a hormone mainly secreted by the pineal gland, which can play a number of functions in the human body such as regulating biological rhythms, scavenging free radicals, and anti-inflammatory. In recent years, studies have shown that melatonin can improve neuronal degeneration and protect blood vessel structure through multiple mechanisms in retinopathy. In terms of its protective effect on the retinal capillary structure, melatonin can improve the damage of early DR endothelial cells and pericytes through anti-oxidative stress, anti-inflammatory, and inhibiting cell apoptosis so as to protect the integrity of the blood-retinal barrier structure. It suggests that melatonin may provide new ideas for the prevention and treatment of DR, especially with DME.

Citation： Sun Dandan, Xu Xun. Protective effects of melatonin on endothelial cells and pericytes in diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2020, 36(9): 745-748. doi: 10.3760/cma.j.cn511434-20190321-00106 Copy

1.	Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol Ⅰ data[J]. Am J Ophthalmol, 2016, 172: 72-79. DOI: 10.1016/j.ajo.2016.09.012.
2.	陈翀, 刘堃. 重视糖尿病黄斑水肿的个体化治疗[J]. 中华眼底病杂志, 2020, 36(2): 89-93. DOI: 10.3760/cma.j.issn.1005-1015.2020.02.001.Chen C, Liu K. Attach importance to individualized treatment of diabetic macular edema[J]. Chin J Ocul Fundus Dis, 2020, 36(2): 89-93. DOI: 10.3760/cma.j.issn.1005-1015.2020.02.001.
3.	许迅, 卢一. 重视对糖尿病黄斑水肿的诊治[J]. 中华眼底病杂志, 2018, 34(4): 313-316. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.001.Xu X, Lu Y. Focusing on the diagnosis and treatment of diabetic macular edema[J]. Chin J Ocul Fundus Dis, 2018, 34(4): 313-316. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.001.
4.	Chitimus DM, Popescu MR, Voiculescu SE, et al. Melatonin’s impact on antioxidative and anti-inflammatory reprogramming in homeostasis and disease[J/OL]. Biomolecules, 2020, 10(9): 1211[2020-08-20]. https://pubmed.ncbi.nlm.nih.gov/32825327/. DOI: 10.3390/biom10091211.
5.	Esquiva G, Hannibal J. Melanopsin-expressing retinal ganglion cells in aging and disease[J]. Histol Histopathol, 2019, 34(12): 1299-1311. DOI: 10.14670/hh-18-138.
6.	Xu XJ, Wang SM, Jin Y, et al. Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa[J/OL]. J Pineal Res, 2017, 63(3): 1[2017-06-20]. https://pubmed.ncbi.nlm.nih.gov/28580724/. DOI: 10.1111/jpi.12428.
7.	Jiang TT, Chang Q, Zhao ZY, et al. Melatonin-mediated cytoprotection against hyperglycemic injury in muller cells[J/OL]. PLoS One, 2012, 7(12): 50661[2012-12-04]. https://pubmed.ncbi.nlm.nih.gov/23226532/. DOI: 10.1371/journal.pone.0050661.
8.	Kaur C, Sivakumar V, Yong Z, et al. Blood-retinal barrier disruption and ultrastructural changes in the hypoxic retina in adult rats: the beneficial effect of melatonin administration[J]. J Pathol, 2007, 212(4): 429-439. DOI: 10.1002/path.2195.
9.	Xu Y, Lu X, Hu Y, et al. Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1alpha-VEGF pathway in oxygen-induced retinopathy mice[J/OL]. J Pineal Res, 2018, 64(4): 12473[2018-03-08]. https://pubmed.ncbi.nlm.nih.gov/29411894/. DOI: 10.1111/jpi.12473.
10.	Ro S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy[J]. Am J Pathol, 2017, 187(1): 9-19. DOI: 10.1016/j.ajpath.2016.08.022.
11.	Kusuhara S, Fukushima Y, Ogura S, et al. Pathophysiology of diabetic retinopathy: the old and the new[J]. Diabetes Metab J, 2018, 42(5): 364-376. DOI: 10.4093/dmj.2018.0182.
12.	Cui Y, Xu X, Bi H, et al. Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy[J]. Exp Eye Res, 2006, 83(4): 807-816. DOI: 10.1016/j.exer.2006.03.024.
13.	Giacco F, Brownlee M. Oxidative stress and diabetic complications[J]. Circ Res, 2010, 107(9): 1058-1070. DOI: 10.1161/circresaha.110.223545.
14.	Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. DOI: 10.1016/j.preteyeres.2011.05.002.
15.	Menini S, Iacobini C, Vitale M, et al. The inflammasome in chronic complications of diabetes and related metabolic disorders[J/OL]. Cells, 2020, 9(8): 1812[2020-07-30]. https://pubmed.ncbi.nlm.nih.gov/32751658/. DOI: 10.3390/cells9081812.
16.	Kaštelan S, Orešković I, Bišćan F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J/OL]. Biochem Med (Zagreb), 2020, 30(3): 030502[2020-10-15]. https://pubmed.ncbi.nlm.nih.gov/32774120/. DOI: 10.11613/bm.2020.030502.
17.	Dehdashtian E, Mehrzadi S, Yousefi B, et al. Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress[J]. Life Sci, 2018, 193: 20-33. DOI: 10.1016/j.lfs.2017.12.001.
18.	Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions[J]. Circ Res, 2005, 97(6): 512-523. DOI: 10.1161/01.RES.0000182903.16652.d7.
19.	Chou J, Rollins S, Fawzi AA. Role of endothelial cell and pericyte dysfunction in diabetic retinopathy: review of techniques in rodent models[J]. Adv Exp Med Biol, 2014, 801: 669-675. DOI: 10.1007/978-1-4614-3209-8_84.
20.	Zephy D, Ahmad J. Type 2 diabetes mellitus: role of melatonin and oxidative stress[J]. Diabetes Metab Syndr, 2015, 9(2): 127-131. DOI: 10.1016/j.dsx.2014.09.018.
21.	Ozdemir G, Ergun Y, Bakaris S, et al. Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats[J]. Eye (Lond), 2014, 28(8): 1020-1027. DOI: 10.1038/eye.2014.127.
22.	Mehrzadi S, Motevalian M, Kanavi MR, et al. Protective effect of melatonin in the diabetic rat retina[J]. Fundam Clin Pharmacol, 2018, 32(4): 414-421. DOI: 10.1111/fcp.12361.
23.	Nabavi SF, Barber AJ, Spagnuolo C, et al. Nrf2 as molecular target for polyphenols: a novel therapeutic strategy in diabetic retinopathy[J]. Crit Rev Clin Lab Sci, 2016, 53(5): 293-312. DOI: 10.3109/10408363.2015.1129530.
24.	Jiang T, Chang Q, Cai J, et al. Protective effects of melatonin on retinal inflammation and oxidative stress in experimental diabetic retinopathy[J/OL]. Oxid Med Cell Longev, 2016, 2016: 3528274[2016-04-06]. https://pubmed.ncbi.nlm.nih.gov/27143993/. DOI: 10.1155/2016/3528274.
25.	Salido EM, Bordone M, De Laurentiis A, et al. Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats[J]. J Pineal Res, 2013, 54(2): 179-189. DOI: 10.1111/jpi.12008.
26.	Rubsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy[J/OL]. Int J Mol Sci, 2018, 19(4): 942[2018-03-22]. https://pubmed.ncbi.nlm.nih.gov/29565290/. DOI: 10.3390/ijms19040942.
27.	Behl Y, Krothapalli P, Desta T, et al. Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy[J]. Am J Pathol, 2008, 172(5): 1411-1418. DOI: 10.2353/ajpath.2008.071070.
28.	Aveleira CA, Lin CM, Abcouwer SF, et al. TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability[J]. Diabetes, 2010, 59(11): 2872-2882. DOI: 10.2337/db09-1606.
29.	Zheng L, Du Y, Miller C, et al. Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes[J]. Diabetologia, 2007, 50(9): 1987-1996. DOI: 10.1007/s00125-007-0734-9.
30.	Leal EC, Manivannan A, Hosoya K, et al. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2007, 48(11): 5257-5265. DOI: 10.1167/iovs.07-0112.
31.	Aranda ML, Fleitas MFG, Dieguez H, et al. Melatonin as a therapeutic resource for inflammatory visual diseases[J]. Curr Neuropharmacol, 2017, 15(7): 951-962. DOI: 10.2174/1570159x15666170113122120.
32.	Giebel SJ, Menicucci G, McGuire PG, et al. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier[J]. Lab Invest, 2005, 85(5): 597-607. DOI: 10.1038/labinvest.3700251.
33.	Xie MY, Hu A, Luo Y, et al. Interleukin-4 and melatonin ameliorate high glucose and interleukin-1 beta stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells[J]. Mol Vis, 2014, 20: 921-928.
34.	Djordjevic B, Cvetkovic T, Stoimenov TJ, et al. Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes[J]. Eur J Pharmacol, 2018, 833: 290-297. DOI: 10.1016/j.ejphar.2018.06.011.
35.	Hardeland R. Melatonin and inflammation-story of a double-edged blade[J/OL]. J Pineal Res, 2018, 65(4): 12525[2018-10-12]. https://pubmed.ncbi.nlm.nih.gov/30242884/. DOI: 10.1111/jpi.12525.
36.	Aranda ML, González Fleitas MF, De Laurentiis A, et al. Neuroprotective effect of melatonin in experimental optic neuritis in rats[J]. J Pineal Res, 2016, 60(3): 360-372. DOI: 10.1111/jpi.12318.
37.	El-Asrar AM, Missotten L, Geboes K. Expression of cyclo-oxygenase-2 and downstream enzymes in diabetic fibrovascular epiretinal membranes[J]. Br J Ophthalmol, 2008, 92(11): 1534-1539. DOI: 10.1136/bjo.2008.142182.
38.	Chang CC, Huang TY, Chen HY, et al. Protective effect of melatonin against oxidative stress-induced apoptosis and enhanced autophagy in human retinal pigment epithelium cells[J/OL]. Oxid Med Cell Longev, 2018, 2018:9015765[2018-08-05]. https://pubmed.ncbi.nlm.nih.gov/30174783/. DOI: 10.1155/2018/9015765.
39.	Ferreira de Melo IM, Martins Ferreira CG, Lima da Silva Souza EH, et al. Melatonin regulates the expression of inflammatory cytokines, VEGF and apoptosis in diabetic retinopathy in rats[J/OL]. Chem Biol Interact, 2020, 327: 109183[2020-08-25]. https://pubmed.ncbi.nlm.nih.gov/32554039/. DOI: 10.1016/j.cbi.2020.109183.
40.	Mehrzadi S, Hemati K, Reiter RJ, et al. Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment[J]. Expert Opin Ther Targets, 2020, 24(4): 359-378. DOI: 10.1080/14728222.2020.1737015.
41.	李光祖, 王晓莉, 李振, 等. 褪黑素对视网膜缺血再灌注损伤大鼠视网膜细胞凋亡的影响及机制探讨[J]. 中华眼底病杂志, 2018, 34(1): 55-59. DOI: 10.3760/cma.j.issn.1005-1015.2018.01.014.Li GZ, Wang XL, Li Z, et al. The effect of melatonin on retinal apoptosis in rats with ischemia-reperfusion injury[J]. Chin J Ocul Fundus Dis, 2018, 34(1): 55-59. DOI: 10.3760/cma.j.issn.1005-1015.2018.01.014.
42.	Ma Y, Zhao Q, Shao Y, et al. Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy via MAPK pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(3 Suppl): S1-8. DOI: 10.26355/eurrev_201908_18620.
43.	Hikichi T, Tateda N, Miura T. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy[J]. Clin Ophthalmol, 2011, 5: 655-660. DOI: 10.2147/opth.s19559.
44.	do Carmo Buonfiglio D, Peliciari-Garcia RA, do Amaral FG, et al. Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats[J]. Invest Ophthalmol Vis Sci, 2011, 52(10): 7416-7422. DOI: 10.1167/iovs.10-6756.
45.	Chen W, Cao H, Lu QY, et al. Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2 diabetes[J]. Int J Clin Exp Pathol, 2014, 7(7): 4317-4322.

1. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of protocol Ⅰ data[J]. Am J Ophthalmol, 2016, 172: 72-79. DOI: 10.1016/j.ajo.2016.09.012.
2. 陈翀, 刘堃. 重视糖尿病黄斑水肿的个体化治疗[J]. 中华眼底病杂志, 2020, 36(2): 89-93. DOI: 10.3760/cma.j.issn.1005-1015.2020.02.001.Chen C, Liu K. Attach importance to individualized treatment of diabetic macular edema[J]. Chin J Ocul Fundus Dis, 2020, 36(2): 89-93. DOI: 10.3760/cma.j.issn.1005-1015.2020.02.001.
3. 许迅, 卢一. 重视对糖尿病黄斑水肿的诊治[J]. 中华眼底病杂志, 2018, 34(4): 313-316. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.001.Xu X, Lu Y. Focusing on the diagnosis and treatment of diabetic macular edema[J]. Chin J Ocul Fundus Dis, 2018, 34(4): 313-316. DOI: 10.3760/cma.j.issn.1005-1015.2018.04.001.
4. Chitimus DM, Popescu MR, Voiculescu SE, et al. Melatonin’s impact on antioxidative and anti-inflammatory reprogramming in homeostasis and disease[J/OL]. Biomolecules, 2020, 10(9): 1211[2020-08-20]. https://pubmed.ncbi.nlm.nih.gov/32825327/. DOI: 10.3390/biom10091211.
5. Esquiva G, Hannibal J. Melanopsin-expressing retinal ganglion cells in aging and disease[J]. Histol Histopathol, 2019, 34(12): 1299-1311. DOI: 10.14670/hh-18-138.
6. Xu XJ, Wang SM, Jin Y, et al. Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa[J/OL]. J Pineal Res, 2017, 63(3): 1[2017-06-20]. https://pubmed.ncbi.nlm.nih.gov/28580724/. DOI: 10.1111/jpi.12428.
7. Jiang TT, Chang Q, Zhao ZY, et al. Melatonin-mediated cytoprotection against hyperglycemic injury in muller cells[J/OL]. PLoS One, 2012, 7(12): 50661[2012-12-04]. https://pubmed.ncbi.nlm.nih.gov/23226532/. DOI: 10.1371/journal.pone.0050661.
8. Kaur C, Sivakumar V, Yong Z, et al. Blood-retinal barrier disruption and ultrastructural changes in the hypoxic retina in adult rats: the beneficial effect of melatonin administration[J]. J Pathol, 2007, 212(4): 429-439. DOI: 10.1002/path.2195.
9. Xu Y, Lu X, Hu Y, et al. Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1alpha-VEGF pathway in oxygen-induced retinopathy mice[J/OL]. J Pineal Res, 2018, 64(4): 12473[2018-03-08]. https://pubmed.ncbi.nlm.nih.gov/29411894/. DOI: 10.1111/jpi.12473.
10. Ro S, Kern TS, Song B, et al. Mechanistic insights into pathological changes in the diabetic retina: implications for targeting diabetic retinopathy[J]. Am J Pathol, 2017, 187(1): 9-19. DOI: 10.1016/j.ajpath.2016.08.022.
11. Kusuhara S, Fukushima Y, Ogura S, et al. Pathophysiology of diabetic retinopathy: the old and the new[J]. Diabetes Metab J, 2018, 42(5): 364-376. DOI: 10.4093/dmj.2018.0182.
12. Cui Y, Xu X, Bi H, et al. Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: the role of reactive oxygen species in diabetic retinopathy[J]. Exp Eye Res, 2006, 83(4): 807-816. DOI: 10.1016/j.exer.2006.03.024.
13. Giacco F, Brownlee M. Oxidative stress and diabetic complications[J]. Circ Res, 2010, 107(9): 1058-1070. DOI: 10.1161/circresaha.110.223545.
14. Tang J, Kern TS. Inflammation in diabetic retinopathy[J]. Prog Retin Eye Res, 2011, 30(5): 343-358. DOI: 10.1016/j.preteyeres.2011.05.002.
15. Menini S, Iacobini C, Vitale M, et al. The inflammasome in chronic complications of diabetes and related metabolic disorders[J/OL]. Cells, 2020, 9(8): 1812[2020-07-30]. https://pubmed.ncbi.nlm.nih.gov/32751658/. DOI: 10.3390/cells9081812.
16. Kaštelan S, Orešković I, Bišćan F, et al. Inflammatory and angiogenic biomarkers in diabetic retinopathy[J/OL]. Biochem Med (Zagreb), 2020, 30(3): 030502[2020-10-15]. https://pubmed.ncbi.nlm.nih.gov/32774120/. DOI: 10.11613/bm.2020.030502.
17. Dehdashtian E, Mehrzadi S, Yousefi B, et al. Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress[J]. Life Sci, 2018, 193: 20-33. DOI: 10.1016/j.lfs.2017.12.001.
18. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions[J]. Circ Res, 2005, 97(6): 512-523. DOI: 10.1161/01.RES.0000182903.16652.d7.
19. Chou J, Rollins S, Fawzi AA. Role of endothelial cell and pericyte dysfunction in diabetic retinopathy: review of techniques in rodent models[J]. Adv Exp Med Biol, 2014, 801: 669-675. DOI: 10.1007/978-1-4614-3209-8_84.
20. Zephy D, Ahmad J. Type 2 diabetes mellitus: role of melatonin and oxidative stress[J]. Diabetes Metab Syndr, 2015, 9(2): 127-131. DOI: 10.1016/j.dsx.2014.09.018.
21. Ozdemir G, Ergun Y, Bakaris S, et al. Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats[J]. Eye (Lond), 2014, 28(8): 1020-1027. DOI: 10.1038/eye.2014.127.
22. Mehrzadi S, Motevalian M, Kanavi MR, et al. Protective effect of melatonin in the diabetic rat retina[J]. Fundam Clin Pharmacol, 2018, 32(4): 414-421. DOI: 10.1111/fcp.12361.
23. Nabavi SF, Barber AJ, Spagnuolo C, et al. Nrf2 as molecular target for polyphenols: a novel therapeutic strategy in diabetic retinopathy[J]. Crit Rev Clin Lab Sci, 2016, 53(5): 293-312. DOI: 10.3109/10408363.2015.1129530.
24. Jiang T, Chang Q, Cai J, et al. Protective effects of melatonin on retinal inflammation and oxidative stress in experimental diabetic retinopathy[J/OL]. Oxid Med Cell Longev, 2016, 2016: 3528274[2016-04-06]. https://pubmed.ncbi.nlm.nih.gov/27143993/. DOI: 10.1155/2016/3528274.
25. Salido EM, Bordone M, De Laurentiis A, et al. Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats[J]. J Pineal Res, 2013, 54(2): 179-189. DOI: 10.1111/jpi.12008.
26. Rubsam A, Parikh S, Fort PE. Role of inflammation in diabetic retinopathy[J/OL]. Int J Mol Sci, 2018, 19(4): 942[2018-03-22]. https://pubmed.ncbi.nlm.nih.gov/29565290/. DOI: 10.3390/ijms19040942.
27. Behl Y, Krothapalli P, Desta T, et al. Diabetes-enhanced tumor necrosis factor-alpha production promotes apoptosis and the loss of retinal microvascular cells in type 1 and type 2 models of diabetic retinopathy[J]. Am J Pathol, 2008, 172(5): 1411-1418. DOI: 10.2353/ajpath.2008.071070.
28. Aveleira CA, Lin CM, Abcouwer SF, et al. TNF-alpha signals through PKCzeta/NF-kappaB to alter the tight junction complex and increase retinal endothelial cell permeability[J]. Diabetes, 2010, 59(11): 2872-2882. DOI: 10.2337/db09-1606.
29. Zheng L, Du Y, Miller C, et al. Critical role of inducible nitric oxide synthase in degeneration of retinal capillaries in mice with streptozotocin-induced diabetes[J]. Diabetologia, 2007, 50(9): 1987-1996. DOI: 10.1007/s00125-007-0734-9.
30. Leal EC, Manivannan A, Hosoya K, et al. Inducible nitric oxide synthase isoform is a key mediator of leukostasis and blood-retinal barrier breakdown in diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2007, 48(11): 5257-5265. DOI: 10.1167/iovs.07-0112.
31. Aranda ML, Fleitas MFG, Dieguez H, et al. Melatonin as a therapeutic resource for inflammatory visual diseases[J]. Curr Neuropharmacol, 2017, 15(7): 951-962. DOI: 10.2174/1570159x15666170113122120.
32. Giebel SJ, Menicucci G, McGuire PG, et al. Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier[J]. Lab Invest, 2005, 85(5): 597-607. DOI: 10.1038/labinvest.3700251.
33. Xie MY, Hu A, Luo Y, et al. Interleukin-4 and melatonin ameliorate high glucose and interleukin-1 beta stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells[J]. Mol Vis, 2014, 20: 921-928.
34. Djordjevic B, Cvetkovic T, Stoimenov TJ, et al. Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes[J]. Eur J Pharmacol, 2018, 833: 290-297. DOI: 10.1016/j.ejphar.2018.06.011.
35. Hardeland R. Melatonin and inflammation-story of a double-edged blade[J/OL]. J Pineal Res, 2018, 65(4): 12525[2018-10-12]. https://pubmed.ncbi.nlm.nih.gov/30242884/. DOI: 10.1111/jpi.12525.
36. Aranda ML, González Fleitas MF, De Laurentiis A, et al. Neuroprotective effect of melatonin in experimental optic neuritis in rats[J]. J Pineal Res, 2016, 60(3): 360-372. DOI: 10.1111/jpi.12318.
37. El-Asrar AM, Missotten L, Geboes K. Expression of cyclo-oxygenase-2 and downstream enzymes in diabetic fibrovascular epiretinal membranes[J]. Br J Ophthalmol, 2008, 92(11): 1534-1539. DOI: 10.1136/bjo.2008.142182.
38. Chang CC, Huang TY, Chen HY, et al. Protective effect of melatonin against oxidative stress-induced apoptosis and enhanced autophagy in human retinal pigment epithelium cells[J/OL]. Oxid Med Cell Longev, 2018, 2018:9015765[2018-08-05]. https://pubmed.ncbi.nlm.nih.gov/30174783/. DOI: 10.1155/2018/9015765.
39. Ferreira de Melo IM, Martins Ferreira CG, Lima da Silva Souza EH, et al. Melatonin regulates the expression of inflammatory cytokines, VEGF and apoptosis in diabetic retinopathy in rats[J/OL]. Chem Biol Interact, 2020, 327: 109183[2020-08-25]. https://pubmed.ncbi.nlm.nih.gov/32554039/. DOI: 10.1016/j.cbi.2020.109183.
40. Mehrzadi S, Hemati K, Reiter RJ, et al. Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment[J]. Expert Opin Ther Targets, 2020, 24(4): 359-378. DOI: 10.1080/14728222.2020.1737015.
41. 李光祖, 王晓莉, 李振, 等. 褪黑素对视网膜缺血再灌注损伤大鼠视网膜细胞凋亡的影响及机制探讨[J]. 中华眼底病杂志, 2018, 34(1): 55-59. DOI: 10.3760/cma.j.issn.1005-1015.2018.01.014.Li GZ, Wang XL, Li Z, et al. The effect of melatonin on retinal apoptosis in rats with ischemia-reperfusion injury[J]. Chin J Ocul Fundus Dis, 2018, 34(1): 55-59. DOI: 10.3760/cma.j.issn.1005-1015.2018.01.014.
42. Ma Y, Zhao Q, Shao Y, et al. Melatonin inhibits the inflammation and apoptosis in rats with diabetic retinopathy via MAPK pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(3 Suppl): S1-8. DOI: 10.26355/eurrev_201908_18620.
43. Hikichi T, Tateda N, Miura T. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy[J]. Clin Ophthalmol, 2011, 5: 655-660. DOI: 10.2147/opth.s19559.
44. do Carmo Buonfiglio D, Peliciari-Garcia RA, do Amaral FG, et al. Early-stage retinal melatonin synthesis impairment in streptozotocin-induced diabetic wistar rats[J]. Invest Ophthalmol Vis Sci, 2011, 52(10): 7416-7422. DOI: 10.1167/iovs.10-6756.
45. Chen W, Cao H, Lu QY, et al. Urinary 6-sulfatoxymelatonin level in diabetic retinopathy patients with type 2 diabetes[J]. Int J Clin Exp Pathol, 2014, 7(7): 4317-4322.

Previous Article
The imaging characteristics of pachychoroidopathy and the research status and progress of pathogenesis and treatment based on the imaging characteristics

Chinese Journal of Ocular Fundus Diseases

Protective effects of melatonin on endothelial cells and pericytes in diabetic retinopathy

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Format

Content