Retinal ischemia-reperfusion injury (RIRI) is an important pathophysiological basis of diabetic retinopathy, glaucoma, central retinal arteriovenous obstruction and some other ischemic retinal diseases. At present, there are several theories about the pathogenesis of RIRI, which included oxidative stress, apoptosis, necrosis, necroptosis, vascular injury and inflammatory reaction. Aim at the above pathogenesis of RIRI, domestic and foreign scholars have put forward a lot of methods in treating RIRI, including anti-radical damage, anti-glutamic acid excitotoxicity, anti-apoptosis, anti-necrosis, anti-necroptosis, protection of tight junctions, protection of endothelial cells, anti-inflammatory response, etc. Although there are a lot of drug research on RIRI, the timing of drug interventions for RIRI is still unclear. It may achieve twice the result with half the effort to determine the most effective treatment time window, and will also play a vital guiding role in the clinical treatment of ophthalmic related diseases.
Citation: Guo Miao, Yan Hua. Research progress in the mechanism and treatment of retinal ischemia reperfusion injury. Chinese Journal of Ocular Fundus Diseases, 2020, 36(6): 483-488. doi: 10.3760/cma.j.cn511434-20180807-00276 Copy
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- 1. Pan H, He M, Liu R, et al. Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway[J/OL]. PLoS One, 2014, 9(12): 114186[2014-12-03]. http://europepmc.org/abstract/MED/25470382. DOI: 10.1371/journal.pone.0114186.
- 2. Gao S, Andreeva K, Cooper NG. Ischemia-reperfusion injury of the retina is linked to necroptosis via the ERK1/2-RIP3 pathway[J]. Mol Vis, 2014, 20: 1374-1387.
- 3. Minhas G, Sharma J, Khan N. Cellular stress response and immune signaling in retinal ischemia-reperfusion injury[J/OL]. Front Immunol, 2016, 7: 444[2016-10-24]. http://europepmc.org/article/MED/27822213. DOI: 10.3389/fimmu.2016.00444.
- 4. Dvoriantchikova G, Barakat D, Brambilla R, et al. Inactivation of astroglial NF-κB promotes survival of retinal neurons following ischemic injury[J]. Eur J Neurosci, 2009, 30(2): 175-185. DOI: 10.1111/j.1460-9568.2009.06814.x.
- 5. Barakat DJ, Dvoriantchikova G, Ivanov DV, et al. Astroglial NF-κB mediates oxidative stress by regulation of NADPH oxidase in a model of retinal ischemia reperfusion injury[J/OL]. J Neurochem, 2012, 120(4): 586597[2012-01-04]. http://europepmc.org/article/PMC/3310387. DOI: 10.1111/j.1471-4159.2011.07595.x.
- 6. Chen Y, Huang Y, Chen J, et al. Protective effects of glucosamine on oxidative-stress and ischemia/reperfusion-induced retinal injury[J]. Invest Ophthalmol Vis Sci, 2015, 56(3): 1506-1516. DOI: 10.1167/iovs.14-15726.
- 7. Ishizuka F, Shimazawa M, Umigai N, et al. Crocetin, a carotenoid derivative, inhibits retinal ischemic damage in mice[J]. Eur J Pharmacol, 2013, 703(1): 1-10. DOI: 10.1016/j.ejphar.2013.02.007.
- 8. Swanson RA, Ying W, Kauppinen TM, et al. Astrocyte influences on ischemic neuronal death[J]. Curr Mol Med, 2004, 4(2): 193-205. DOI: 10.2174/1566524043479185.
- 9. Lan A, Liao X, Mo L, et al. Hydrogen sulfide protects against chemical hypoxia-induced injury by inhibiting ROS-activated ERK1/2 and p38MAPK signaling pathways in PC12 cells[J/OL]. PLoS One, 2011, 6(10): 25921[2011-10-05]. http://europepmc.org/article/PMC/3187826. DOI: 10.1371/journal.pone.0025921.
- 10. Xu Z, Cho H, Hartsock MJ, et al. Neuroprotective role of Nrf2 for retinal ganglion cells in ischemia-reperfusion[J]. J Neurochem, 2015, 133(2): 233-241. DOI: 10.1111/jnc.13064.
- 11. Wei Y, Gong J, Yoshida T, et al. Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia-reperfusion injury[J]. Free Radic Biol Med, 2011, 51(1): 216-224. DOI: 10.1016/j.freeradbiomed.2011.04.026.
- 12. Himori N, Yamamoto K, Maruyama K, et al. Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death[J]. J Neurochem, 2013, 127(5): 669-680. DOI: 10.1111/jnc.12325.
- 13. Lee D, Kim K, Noh YH, et al. Brimonidine blocks glutamate excitotoxicity-induced oxidative stress and preserves mitochondrial transcription factor a in ischemic retinal injury[J/OL]. PLoS One, 2012, 7(10): 47098[2012-10-09]. http://europepmc.org/article/PMC/3467218. DOI: 10.1371/journal.pone.0047098.
- 14. Fukuda K, Hirooka K, Mizote M, et al. Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin Ⅱ type 1 receptor[J]. Invest Ophthalmol Vis Sci, 2010, 51(7): 3629-3638. DOI: 10.1167/iovs.09-4107.
- 15. Fujita T, Hirooka K, Nakamura T, et al. Neuroprotective effects of angiotensin Ⅱ type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels[J]. Invest Ophthalmol Vis Sci, 2012, 53(7): 4099-4110. DOI: 10.1167/iovs.11-9167.
- 16. Arikan S, Ersan I, Karaca T, et al. Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model[J]. Arq Bras Oftalmol, 2015, 78(2): 100-104. DOI: 10.5935/0004-2749.20150026.
- 17. Gencer B, Karaca T, Tufan HA, et al. The protective effects of dexmedetomidine against apoptosis in retinal ischemia/reperfusion injury in rats[J]. Cutan Ocul Toxicol, 2014, 33(4): 283-288. DOI: 10.3109/15569527.2013.857677.
- 18. Zhang Y, Zhang Z, Yan H, et al. Simvastatin inhibits ischemia/reperfusion injury-induced apoptosis of retinal cells via downregulation of the tumor necrosis factor-α/nuclear factor-κB pathway[J]. Int J Mol Med, 2015, 36(2): 399-405. DOI: 10.3892/ijmm.2015.2244.
- 19. Zhang Z, Qin X, Tong N, et al. Valproic acid-mediated neuroprotection in retinal ischemia injury via histone deacetylase inhibition and transcriptional activation[J]. Exp Eye Res, 2012, 94(1): 98-108. DOI: 10.1016/j.exer.2011.11.013.
- 20. Chen Q, Wang H, Liao S, et al. Nerve growth factor protects retinal ganglion cells against injury induced by retinal ischemia-reperfusion in rats[J]. Growth Factors, 2015, 33(2): 149-159. DOI: 10.3109/08977194.2015.1010642.
- 21. Shima C, Adachi Y, Minamino K, et al. Neuroprotective effects of granulocyte colony-stimulating factor on ischemia-reperfusion injury of the retina[J]. Ophthalmic Res, 2012, 48(4): 199-207. DOI: 10.1159/000340059.
- 22. Qi Y, Chen L, Zhang L, et al. Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway[J]. Exp Eye Res, 2013, 107: 44-51. DOI: 10.1016/j.exer.2012.11.011.
- 23. Wu J, Wang R, Yang D, et al. Hydrogen postconditioning promotes survival of rat retinal ganglion cells against ischemia/reperfusion injury through the PI3K/Akt pathway[J]. Biochem Biophys Res Commun, 2018, 495(4): 2462-2468. DOI: 10.1016/j.bbrc.2017.12.146.
- 24. Zhang SX, Sanders E, Fliesler SJ, et al. Endoplasmic reticulum stress and the unfolded protein responses in retinal degeneration[J]. Exp Eye Res, 2014, 125: 30-40. DOI: 10.1111/febs.14522.
- 25. Jing G, Wang JJ, Zhang SX, et al. ER stress and apoptosis: a new mechanism for retinal cell death[J/OL]. Exp Diabetes Res, 2012, 2012: 589589[2011-12-14]. http://europepmc.org/article/PMC/3246718. DOI: 10.1002/jcp.28100.
- 26. Zhang Z, Tong N, Gong Y, et al. Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis after ischemia-reperfusion injury[J]. Neurosci Lett, 2011, 504(2): 88-92. DOI: 10.1016/j.neulet.2011.09.003.
- 27. Rosenbaum DM, Degterev A, David J, et al. Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model[J]. J Neurosci Res, 2010, 88(7): 1569-1576. DOI: 10.1002/jnr.22314.
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