活性氧(reactive oxygen species, ROS)是在氧化磷酸化过程中产生的,在细胞及组织的增殖、分化及凋亡等方面发挥着重要作用。大量研究表明,ROS与视网膜母细胞瘤、葡萄膜黑色素瘤、年龄相关性黄斑变性、年龄相关性白内障、干眼症、翼状胬肉等眼部相关疾病的发生、发展密切相关。本文主要针对ROS的作用机制及在眼部相关疾病中的研究现况进行阐述,为进一步研究眼部相关疾病及治疗提供参考依据。
Reactive oxygen species (ROS) is produced in the process of oxidative phosphorylation, and plays an important role in proliferation, differentiation and apoptosis of cells and tissues. A large number of studies have shown that ROS is closely related to the occurrence and development of eye related diseases such as Retinoblastoma, Uveal Melanoma, Age-Related Macular Degeneration, Age- Related Cataract, Dry Eye and Pterygium. In this article, the mechanism of ROS and the research status of ROS in eye related diseases were expounded, so as to provide reference for further research on ophthalmic diseases and treatment.
Reactive oxygen species (ROS) is produced in the process of oxidative phosphorylation, and plays an important role in proliferation, differentiation and apoptosis of cells and tissues. A large number of studies have shown that ROS is closely related to the occurrence and development of eye related diseases such as Retinoblastoma, Uveal Melanoma, Age-Related Macular Degeneration, Age- Related Cataract, Dry Eye and Pterygium. In this article, the mechanism of ROS and the research status of ROS in eye related diseases were expounded, so as to provide reference for further research on ophthalmic diseases and treatment.
张雯洁,刘静雯,卢怡洁,秦 波. 活性氧在眼科疾病的研究现状和进展Research Status and Progress of Reactive Oxygen Species in Ophthalmic Diseases[J]. 临床医学进展, 2021, 11(09): 4092-4098. https://doi.org/10.12677/ACM.2021.119597
参考文献ReferencesKowluru, R. (2021) Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road. Antioxidants (Basel, Switzerland), 10, 783. <br>https://doi.org/10.3390/antiox10050783Syed Mortadza, S., Wang, L., Li, D., et al. (2015) TRPM2 Channel-Mediated ROS-Sensitive Ca2+ Signaling Mechanisms in Immune Cells. Frontiers in Immunology, 6, 407. <br>https://doi.org/10.3389/fimmu.2015.00407Zou, Z., Chang, H., Li, H., et al. (2017) Induction of Reactive Oxygen Species: An Emerging Approach for Cancer Therapy. Apoptosis: An International Journal on Programmed Cell Death, 22, 1321-1335.
<br>https://doi.org/10.1007/s10495-017-1424-9Jin, Y., Huynh, D.T.N., Nguyen, T.L.L., et al. (2020) Therapeutic Effects of Ginsenosides on Breast Cancer Growth and Metastasis. Archives of Pharmacal Research, 43, 773-787. <br>https://doi.org/10.1007/s12272-020-01265-8Dröge, W. (2002) Free Radicals in the Physiological Control of Cell Function. Physiological Reviews, 82, 47-95.
<br>https://doi.org/10.1152/physrev.00018.2001Shadel, G.S. and Horvath, T.L. (2015) Mitochondrial ROS Signaling in Organismal Homeostasis. Cell, 163, 560-569.
<br>https://doi.org/10.1016/j.cell.2015.10.001Sauer, H., Wartenberg, M. and Hescheler, J. (2001) Reactive Oxygen Species as Intracellular Messengers during Cell Growth and Differentiation. Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 11, 173-186. <br>https://doi.org/10.1159/000047804Lesnefsky, E.J., Moghaddas, S., Tandler, B., et al. (2001) Mitochondrial Dysfunction in Cardiac Disease: Ischemia— Reperfusion, Aging, and Heart Failure. Journal of Molecular and Cellular Cardiology, 33, 1065-1089.
<br>https://doi.org/10.1006/jmcc.2001.1378Chen, Q., Vazquez, E.J., Moghaddas, S., et al. (2003) Production of Reactive Oxygen Species by Mitochondria: Central Role of Complex III. The Journal of Biological Chemistry, 278, 36027-36031.
<br>https://doi.org/10.1074/jbc.M304854200Saccà, S., Roszkowska, A. and Izzotti, A. (2013) Environmental Light and Endogenous Antioxidants as the Main Determinants of Non-Cancer Ocular Diseases. Mutation Research, 752, 153-171.
<br>https://doi.org/10.1016/j.mrrev.2013.01.001Saccà, S.C., Cutolo, C.A., Ferrari, D., et al. (2018) The Eye, Oxidative Damage and Polyunsaturated Fatty Acids. Nutrients, 10, 668. <br>https://doi.org/10.3390/nu10060668Valko, M., Leibfritz, D., Moncol, J., et al. (2007) Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. The International Journal of Biochemistry & Cell Biology, 39, 44-84.
<br>https://doi.org/10.1016/j.biocel.2006.07.001Klump, K.E. and Mcginnis, J.F. (2014) The Role of Reactive Oxygen Species in Ocular Malignancy. Advances in Experimental Medicine and Biology, 801, 655-659. <br>https://doi.org/10.1007/978-1-4614-3209-8_82Van Reyk, D., Gillies, M. and Davies, M. (2003) The Retina: Oxidative Stress and Diabetes. Redox Report: Communications in Free Radical Research, 8, 187-192. <br>https://doi.org/10.1179/135100003225002673Zhang, D., Gao, C., Li, R., et al. (2017) TEOA, a Triterpenoid from Actinidia eriantha, Induces Autophagy in SW620 Cells via Endoplasmic Reticulum Stress and ROS-Dependent Mitophagy. Archives of Pharmacal Research, 40, 579-591.
<br>https://doi.org/10.1007/s12272-017-0899-9Jeon, H., Huynh, D.T.N., Baek, N., et al. (2021) Ginsenoside-Rg2 Affects Cell Growth via Regulating ROS-Mediated AMPK Activation and Cell Cycle in MCF-7 Cells. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 85, Article ID: 153549. <br>https://doi.org/10.1016/j.phymed.2021.153549Wu, Q., Deng, J., Fan, D., et al. (2018) Ginsenoside Rh4 Induces Apoptosis and Autophagic Cell Death through Activation of the ROS/JNK/p53 Pathway in Colorectal Cancer Cells. Biochemical Pharmacology, 148, 64-74.
<br>https://doi.org/10.1016/j.bcp.2017.12.004Yang, L., Moss, T., Mangala, L.S., et al. (2014) Metabolic Shifts toward Glutamine Regulate Tumor Growth, Invasion and Bioenergetics in Ovarian Cancer. Molecular Systems Biology, 10, 728. <br>https://doi.org/10.1002/msb.20134892Li, L., Fath, M.A., Scarbrough, P.M., et al. (2015) Combined Inhibition of Glycolysis, the Pentose Cycle, and Thioredoxin Metabolism Selectively Increases Cytotoxicity and Oxidative Stress in Human Breast and Prostate Cancer. Redox Biology, 4, 127-135. <br>https://doi.org/10.1016/j.redox.2014.12.001Tahmasebi, G., Eslami, E., Naserzadeh, P., et al. (2020) Role of Mitochondria and Lysosomes in the Selective Cytotoxicity of Cold Atmospheric Plasma on Retinoblastoma Cells. Iranian Journal of Pharmaceutical Research: IJPR, 19, 203-215.Pelicano, H., Carney, D. and Huang, P. (2004) ROS Stress in Cancer Cells and Therapeutic Implications. Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy, 7, 97-110.
<br>https://doi.org/10.1016/j.drup.2004.01.004Trachootham, D., Zhou, Y., Zhang, H., et al. (2006) Selective Killing of Oncogenically Transformed Cells through a ROS-Mediated Mechanism by Beta-Phenylethyl Isothiocyanate. Cancer Cell, 10, 241-252.
<br>https://doi.org/10.1016/j.ccr.2006.08.009Moloney, J. and Cotter, T. (2018) ROS Signalling in the Biology of Cancer. Seminars in Cell & Developmental Biology, 80, 50-64. <br>https://doi.org/10.1016/j.semcdb.2017.05.023Kivelä, T. (2009) The Epidemiological Challenge of the Most Frequent Eye Cancer: Retinoblastoma, an Issue of Birth and Death. The British Journal of Ophthalmology, 93, 1129-1131. <br>https://doi.org/10.1136/bjo.2008.150292Sun, J., Xi, H.Y., Shao, Q., et al. (2020) Biomarkers in Retinoblastoma. International Journal of Ophthalmology, 13, 325-341. <br>https://doi.org/10.18240/ijo.2020.02.18Kaliki, S. and Shields, C.L. (2017) Uveal Melanoma: Relatively Rare but Deadly Cancer. Eye (London, England), 31, 241-257. <br>https://doi.org/10.1038/eye.2016.275Vandhana, S., Lakshmi, T.S., Indra, D., et al. (2012) Microarray Analysis and Biochemical Correlations of Oxidative Stress Responsive Genes in Retinoblastoma. Current Eye Research, 37, 830-841.
<br>https://doi.org/10.3109/02713683.2012.678544Zhu, X., Li, X. and Chen, Z. (2020) Inhibition of Anticancer Growth in Retinoblastoma Cells by Naturally Occurring Sesquiterpene Nootkatone Is Mediated via Autophagy, Endogenous ROS Production, Cell Cycle Arrest and Inhibition of NF-κB Signalling Pathway. Journal of BUON: Official Journal of the Balkan Union of Oncology, 25, 427-431.Guiying, T., Yue, L., Chao, X., et al. (2019) Antitumor Effects of 8-Deoxylactucin in RB355 Human Retinoblastoma Cells Are Mediated via Apoptosis Induction, Reactive Oxygen Species Production, and Cell Cycle Arrest. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 25, 4575-4582.
<br>https://doi.org/10.12659/MSM.914242Yan, F., Liao, R., Silva, M., Li, S., et al. (2020) Pristimerin-Induced Uveal Melanoma Cell Death via Inhibiting PI3K/ Akt/FoxO3a Signalling Pathway. Journal of Cellular and Molecular Medicine, 24, 6208-6219.
<br>https://doi.org/10.1111/jcmm.15249Kaarniranta, K., Pawlowska, E., Szczepanska, J., et al. (2019) Role of Mitochondrial DNA Damage in ROS-Mediated Pathogenesis of Age-Related Macular Degeneration (AMD). International Journal of Molecular Sciences, 20, 2374.
<br>https://doi.org/10.3390/ijms20102374Babizhayev, M. (2016) Generation of Reactive Oxygen Species in the Anterior Eye Segment. Synergistic Codrugs of N-Acetylcarnosine Lubricant Eye Drops and Mitochondria-Targeted Antioxidant Act as a Powerful Therapeutic Platform for the Treatment of Cataracts and Primary Open-Angle Glaucoma. BBA Clinical, 6, 49-68.
<br>https://doi.org/10.1016/j.bbacli.2016.04.004Brennan, L. and Kantorow, M. (2009) Mitochondrial Function and Redox Control in the Aging Eye: Role of MsrA and Other Repair Systems in Cataract and Macular Degenerations. Experimental Eye Research, 88, 195-203.
<br>https://doi.org/10.1016/j.exer.2008.05.018Yao, K., Ye, P., Zhang, L., et al. (2008) Epigallocatechin Gallate Protects against Oxidative Stress-Induced Mitochondria-Dependent Apoptosis in Human Lens Epithelial Cells. Molecular Vision, 14, 217-223.Kruk, J., Kubasik-Kladna, K. and Aboul-Enein, H. (2015) The Role Oxidative Stress in the Pathogenesis of Eye Diseases: Current Status and a Dual Role of Physical Activity. Mini Reviews in Medicinal Chemistry, 16, 241-257.
<br>https://doi.org/10.2174/1389557516666151120114605Babizhayev, M., Deyev, A., Yermakova, V., et al. (2004) Lipid Peroxidation and Cataracts: N-Acetylcarnosine as a Therapeutic Tool to Manage Age-Related Cataracts in Human and in Canine Eyes. Drugs in R&D, 5, 125-139.
<br>https://doi.org/10.2165/00126839-200405030-00001Ganea, E. and Harding, J. (2006) Glutathione-Related Enzymes and the Eye. Current Eye Research, 31, 1-11.
<br>https://doi.org/10.1080/02713680500477347Pennington, K.L. and Deangelis, M.M. (2016) Epidemiology of Age-Related Macular Degeneration (AMD): Associations with Cardiovascular Disease Phenotypes and Lipid Factors. Eye and Vision (London, England), 3, Article No. 34.
<br>https://doi.org/10.1186/s40662-016-0063-5Rohowetz, L.J., Kraus, J.G. and Koulen, P. (2018) Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina. International Journal of Molecular Sciences, 19, 3362. <br>https://doi.org/10.3390/ijms19113362Payne, A.J., Kaja, S., Sabates, N.R., et al. (2013) A Case for Neuroprotection in Ophthalmology: Developments in Translational Research. Missouri Medicine, 110, 429-436.Blasiak, J. (2020) Senescence in the Pathogenesis of Age-Related Macular Degeneration. Cellular and Molecular Life Sciences, 77, 789-805. <br>https://doi.org/10.1007/s00018-019-03420-xHe, Y., Leung, K.W., Zhang, Y.H., et al. (2008) Mitochondrial Complex I Defect Induces ROS Release and Degeneration in Trabecular Meshwork Cells of POAG Patients: Protection by Antioxidants. Investigative Ophthalmology & Visual Science, 49, 1447-1458. <br>https://doi.org/10.1167/iovs.07-1361Zheng, Z., Chen, H., Wang, H., et al. (2010) Improvement of Retinal Vascular Injury in Diabetic Rats by Statins Is Associated with the Inhibition of Mitochondrial Reactive Oxygen Species Pathway Mediated by Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1α. Diabetes, 59, 2315-2325. <br>https://doi.org/10.2337/db10-0638Ruan, Y., Jiang, S., Musayeva, A., et al. (2020) Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies. Antioxidants (Basel, Switzerland), 9, 761. <br>https://doi.org/10.3390/antiox9080761Panahi, Y., Ahmadi, Y., Teymouri, M., et al. (2018) Curcumin as a Potential Candidate for Treating Hyperlipidemia: A Review of Cellular and Metabolic Mechanisms. Journal of Cellular Physiology, 233, 141-152.
<br>https://doi.org/10.1002/jcp.25756Shimouchi, A., Yokota, H., Ono, S., et al. (2016) Neuroprotective Effect of Water-Dispersible Hesperetin in Retinal Ischemia Reperfusion Injury. Japanese Journal of Ophthalmology, 60, 51-61.
<br>https://doi.org/10.1007/s10384-015-0415-zUchino, Y., Kawakita, T., Miyazawa, M., et al. (2012) Oxidative Stress Induced Inflammation Initiates Functional Decline of Tear Production. PLoS ONE, 7, e45805. <br>https://doi.org/10.1371/journal.pone.0045805Balci, M., Sahin, S., Mutlu, F.M., et al. (2011) Investigation of Oxidative Stress in Pterygium Tissue. Molecular Vision, 17, 443-447.Dogru, M., Kojima, T., Simsek, C., et al. (2018) Potential Role of Oxidative Stress in Ocular Surface Inflammation and Dry Eye Disease. Investigative Ophthalmology & Visual Science, 59, DES163-DES168.
<br>https://doi.org/10.1167/iovs.17-23402Wakamatsu, T., Dogru, M., Matsumoto, Y., et al. (2013) Evaluation of Lipid Oxidative Stress Status in Sjögren Syndrome Patients. Investigative Ophthalmology & Visual Science, 54, 201-210. <br>https://doi.org/10.1167/iovs.12-10325Zheng, Q., Ren, Y., Reinach, P.S., et al. (2015) Reactive Oxygen Species Activated NLRP3 Inflammasomes Initiate Inflammation in Hyperosmolarity Stressed Human Corneal Epithelial Cells and Environment-Induced Dry Eye Patients. Experimental Eye Research, 134, 133-140. <br>https://doi.org/10.1016/j.exer.2015.02.013Zhu, C., Pan, F., Ge, L., et al. (2014) SERPINA3K Plays Antioxidant Roles in Cultured Pterygial Epithelial Cells through Regulating ROS System. PLoS ONE, 9, e108859. <br>https://doi.org/10.1371/journal.pone.0108859Tsai, Y., Cheng, Y., Lee, H., et al. (2005) Oxidative DNA Damage in Pterygium. Molecular Vision, 11, 71-75.Frey, T. and Antonetti, D.A. (2011) Alterations to the Blood-Retinal Barrier in Diabetes: Cytokines and Reactive Oxygen Species. Antioxidants & Redox Signaling, 15, 1271-1284. <br>https://doi.org/10.1089/ars.2011.3906Castilho, Á., Aveleira, C.A., Leal, E.C., et al. (2012) Heme Oxygenase-1 Protects Retinal Endothelial Cells against High Glucose- and Oxidative/Nitrosative Stress-Induced Toxicity. PLoS ONE, 7, e42428.
<br>https://doi.org/10.1371/journal.pone.0042428Silva, K., Rosales, M., Biswas, S., et al. (2009) Diabetic Retinal Neurodegeneration Is Associated with Mitochondrial Oxidative Stress and Is Improved by an Angiotensin Receptor Blocker in a Model Combining Hypertension and Diabetes. Diabetes, 58, 1382-1390. <br>https://doi.org/10.2337/db09-0166Santana-Garrido, Á., Reyes-Goya, C., Fernández-Bobadilla, C., et al. (2021) NADPH Oxidase-Induced Oxidative Stress in the Eyes of Hypertensive Rats. Molecular Vision, 27, 161-178.Iomdina, E.N., Khoroshilova-Maslova, I.P., Robustova, O.V., et al. (2015) Mitochondria-Targeted Antioxidant SkQ1 Reverses Glaucomatous Lesions in Rabbits. Frontiers in Bioscience (Landmark Edition), 20, 892-901.
<br>https://doi.org/10.2741/4343Ikuno, Y. (2017) Overview of the Complications of High Myopia. Retina (Philadelphia, PA), 37, 2347-2351.
<br>https://doi.org/10.1097/IAE.0000000000001489Francisco, B.M., Salvador, M. and Amparo, N. (2015) Oxidative Stress in Myopia. Oxidative Medicine and Cellular Longevity, 2015, Article ID: 750637. <br>https://doi.org/10.1155/2015/750637