Oxidative stress in the trabecular meshwork (Review)

Zhao,Jing; Wang,Shuang; Zhong,Wei; Yang,Ben; Sun,Lixia; Zheng,Yajuan

doi:10.3892/ijmm.2016.2714

Oxidative stress in the trabecular meshwork (Review)

Authors:
- Jing Zhao
- Shuang Wang
- Wei Zhong
- Ben Yang
- Lixia Sun
- Yajuan Zheng
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Affiliations: Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Ophthalmology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130031, P.R. China
Published online on: August 24, 2016 https://doi.org/10.3892/ijmm.2016.2714
Pages: 995-1002

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Abstract

Glaucoma is the second leading cause of blindness worldwide and elevated intraocular pressure (IOP) is the most important risk factor. High IOP usually occurs as a result of an increase in aqueous humor outflow resistance at the trabecular meshwork (TM). An abnormal TM contributes to the development of glaucoma. Oxidative stress and vascular damage are considered two major cellular factors that lead to alterations in the TM. In this review, we discuss the findings related to oxidative damage to the TM, including the sources of oxidative stress in the TM such as the mitochondria, peroxisomes, endoplasmic reticulum, membrane, cytosol and exogenous factors. We also discuss antioxidants and clinical studies related to protection against oxidative stress in the TM. Although many questions remain unanswered, it is becoming increasingly clear that oxidative stress-induced damage to the TM is related to glaucoma. This may inspire new studies to find better and more stable antioxidants, and better models with which to elucidate the mechanisms involved, and to determine whether in vitro findings translate into in vivo observations. The regulation of the oxidative/redox balance may be the ultimate target for protecting the TM from oxidative stress and preventing glaucoma.

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1	Kingman S: Glaucoma is second leading cause of blindness globally. Bull World Health Organ. 82:887–888. 2004.
2	Bojikian KD, Moore DB, Chen PP and Slabaugh MA: Optic disc hemorrhage after phacoemulsification in patients with glaucoma. ISRN Ophthalmol. 2014:5740542014. View Article : Google Scholar : PubMed/NCBI
3	Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK II, Wilson MR and Gordon MO: The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 120:701–830. 2002. View Article : Google Scholar : PubMed/NCBI
4	Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B and Hussein M; Early Manifest Glaucoma Trial Group: Reduction of intraocular pressure and glaucoma progression: Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 120:1268–1279. 2002. View Article : Google Scholar : PubMed/NCBI
5	Yue BY: The extracellular matrix and its modulation in the trabecular meshwork. Surv Ophthalmol. 40:379–390. 1996. View Article : Google Scholar : PubMed/NCBI
6	Flammer J: The vascular concept of glaucoma. Surv Ophthalmol. 38(Suppl): S3–S6. 1994. View Article : Google Scholar : PubMed/NCBI
7	Shen F, Chen B, Danias J, Lee KC, Lee H, Su Y, Podos SM and Mittag TW: Glutamate-induced glutamine synthetase expression in retinal Muller cells after short-term ocular hypertension in the rat. Invest Ophthalmol Vis Sci. 45:3107–3112. 2004. View Article : Google Scholar : PubMed/NCBI
8	Galassi F, Renieri G, Sodi A, Ucci F, Vannozzi L and Masini E: Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma. Br J Ophthalmol. 88:757–760. 2004. View Article : Google Scholar : PubMed/NCBI
9	Chung HS, Harris A, Evans DW, Kagemann L, Garzozi HJ and Martin B: Vascular aspects in the pathophysiology of glaucomatous optic neuropathy. Surv Ophthalmol. 43(Suppl 1): S43–S50. 1999. View Article : Google Scholar : PubMed/NCBI
10	Lütjen-Drecoll E: Morphological changes in glaucomatous eyes and the role of TGFbeta2 for the pathogenesis of the disease. Exp Eye Res. 81:1–4. 2005. View Article : Google Scholar : PubMed/NCBI
11	Dalle-Donne I, Rossi R, Colombo R, Giustarini D and Milzani A: Biomarkers of oxidative damage in human disease. Clin Chem. 52:601–623. 2006. View Article : Google Scholar : PubMed/NCBI
12	Weidinger A and Kozlov AV: Biological activities of reactive oxygen and nitrogen species: Oxidative stress versus signal transduction. Biomolecules. 5:472–484. 2015. View Article : Google Scholar : PubMed/NCBI
13	Giustarini D, Dalle-Donne I, Tsikas D and Rossi R: Oxidative stress and human diseases: Origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci. 46:241–281. 2009. View Article : Google Scholar : PubMed/NCBI
14	Babizhayev MA: Lipid fluorophores of the human crystalline lens with cataract. Graefes Arch Clin Exp Ophthalmol. 227:384–391. 1989. View Article : Google Scholar : PubMed/NCBI
15	Green K: Free radicals and aging of anterior segment tissues of the eye: A hypothesis. Ophthalmic Res. 27(Suppl 1): 143–149. 1995. View Article : Google Scholar : PubMed/NCBI
16	Jezek P and Hlavatá L: Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol. 37:2478–2503. 2005. View Article : Google Scholar : PubMed/NCBI
17	Turrens JF: Mitochondrial formation of reactive oxygen species. J Physiol. 552:335–344. 2003. View Article : Google Scholar : PubMed/NCBI
18	Rinnerthaler M, Bischof J, Streubel MK, Trost A and Richter K: Oxidative stress in aging human skin. Biomolecules. 5:545–589. 2015. View Article : Google Scholar : PubMed/NCBI
19	Harman D: The biologic clock: The mitochondria? J Am Geriatr Soc. 20:145–147. 1972. View Article : Google Scholar : PubMed/NCBI
20	Chance B, Sies H and Boveris A: Hydroperoxide metabolism in mammalian organs. Physiol Rev. 59:527–605. 1979.PubMed/NCBI
21	Muller FL, Lustgarten MS, Jang Y, Richardson A and Van Remmen H: Trends in oxidative aging theories. Free Radic Biol Med. 43:477–503. 2007. View Article : Google Scholar : PubMed/NCBI
22	Fransen M, Nordgren M, Wang B and Apanasets O: Role of peroxisomes in ROS/RNS-metabolism: Implications for human disease. Biochim Biophys Acta. 1822:1363–1373. 2012. View Article : Google Scholar
23	Harrison R: Structure and function of xanthine oxidoreductase: Where are we now? Free Radic Biol Med. 33:774–797. 2002. View Article : Google Scholar : PubMed/NCBI
24	Bae YS, Oh H, Rhee SG and Yoo YD: Regulation of reactive oxygen species generation in cell signaling. Mol Cells. 32:491–509. 2011. View Article : Google Scholar : PubMed/NCBI
25	Gorsky LD, Koop DR and Coon MJ: On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem. 259:6812–6817. 1984.PubMed/NCBI
26	Benham AM, van Lith M, Sitia R and Braakman I: Ero1-PDI interactions, the response to redox flux and the implications for disulfide bond formation in the mammalian endoplasmic reticulum. Philos Trans R Soc Lond B Biol Sci. 368:201104032013. View Article : Google Scholar : PubMed/NCBI
27	Bhandary B, Marahatta A, Kim HR and Chae HJ: An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. Int J Mol Sci. 14:434–456. 2012. View Article : Google Scholar : PubMed/NCBI
28	Rinnerthaler M, Büttner S, Laun P, Heeren G, Felder TK, Klinger H, Weinberger M, Stolze K, Grousl T, Hasek J, et al: Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive oxygen species generation, apoptosis, and actin cable formation in yeast. Proc Natl Acad Sci USA. 109:8658–8663. 2012. View Article : Google Scholar : PubMed/NCBI
29	Block K, Gorin Y and Abboud HE: Subcellular localization of Nox4 and regulation in diabetes. Proc Natl Acad Sci USA. 106:14385–14390. 2009. View Article : Google Scholar : PubMed/NCBI
30	Krause KH: Tissue distribution and putative physiological function of NOX family NADPH oxidases. Jpn J Infect Dis. 57:S28–S29. 2004.PubMed/NCBI
31	Nauseef WM: Biological roles for the NOX family NADPH oxidases. J Biol Chem. 283:16961–16965. 2008. View Article : Google Scholar : PubMed/NCBI
32	Kukreja RC, Kontos HA, Hess ML and Ellis EF: PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res. 59:612–619. 1986. View Article : Google Scholar : PubMed/NCBI
33	Norren DV and Vos JJ: Spectral transmission of the human ocular media. Vision Res. 14:1237–1244. 1974. View Article : Google Scholar : PubMed/NCBI
34	Spector A: Oxidative stress-induced cataract: Mechanism of action. FASEB J. 9:1173–1182. 1995.PubMed/NCBI
35	Bryszewska M, Piasecka A, Zavodnik LB, Distel L and Schüssler H: Oxidative damage of Chinese hamster fibroblasts induced by t-butyl hydroperoxide and by X-rays. Biochim Biophys Acta. 1621:285–291. 2003. View Article : Google Scholar : PubMed/NCBI
36	Saccà SC, Pulliero A and Izzotti A: The dysfunction of the trabecular meshwork during glaucoma course. J Cell Physiol. 230:510–525. 2015. View Article : Google Scholar
37	Shoham A, Hadziahmetovic M, Dunaief JL, Mydlarski MB and Schipper HM: Oxidative stress in diseases of the human cornea. Free Radic Biol Med. 45:1047–1055. 2008. View Article : Google Scholar : PubMed/NCBI
38	Alvarado J, Murphy C and Juster R: Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals. Ophthalmology. 91:564–579. 1984. View Article : Google Scholar : PubMed/NCBI
39	Kahn MG, Giblin FJ and Epstein DL: Glutathione in calf trabecular meshwork and its relation to aqueous humor outflow facility. Invest Ophthalmol Vis Sci. 24:1283–1287. 1983.PubMed/NCBI
40	Wielgus AR and Sarna T: Ascorbate enhances photogeneration of hydrogen peroxide mediated by the iris melanin. Photochem Photobiol. 84:683–691. 2008. View Article : Google Scholar : PubMed/NCBI
41	Spector A and Garner WH: Hydrogen peroxide and human cataract. Exp Eye Res. 33:673–681. 1981. View Article : Google Scholar : PubMed/NCBI
42	Sundaresan M, Yu ZX, Ferrans VJ, Irani K and Finkel T: Requirement for generation of H₂O₂ for platelet-derived growth factor signal transduction. Science. 270:296–299. 1995. View Article : Google Scholar : PubMed/NCBI
43	Gulati P, Klöhn PC, Krug H, Göttlicher M, Markova B, Böhmer FD and Herrlich P: Redox regulation in mammalian signal transduction. IUBMB Life. 52:25–28. 2001. View Article : Google Scholar
44	Beckman KB and Ames BN: Mitochondrial aging: Open questions. Ann NY Acad Sci. 854:118–127. 1998. View Article : Google Scholar
45	Balansky R, Izzotti A, Scatolini L, D'Agostini F and De Flora S: Induction by carcinogens and chemoprevention by N-acetylcysteine of adducts to mitochondrial DNA in rat organs. Cancer Res. 56:1642–1647. 1996.PubMed/NCBI
46	de Grey AD: A proposed refinement of the mitochondrial free radical theory of aging. Bioessays. 19:161–166. 1997. View Article : Google Scholar : PubMed/NCBI
47	Dean RT, Fu S, Stocker R and Davies MJ: Biochemistry and pathology of radical-mediated protein oxidation. Biochem J. 324:1–18. 1997. View Article : Google Scholar : PubMed/NCBI
48	Izzotti A, Saccà SC, Longobardi M and Cartiglia C: Sensitivity of ocular anterior chamber tissues to oxidative damage and its relevance to the pathogenesis of glaucoma. Invest Ophthalmol Vis Sci. 50:5251–5258. 2009. View Article : Google Scholar : PubMed/NCBI
49	Clopton DA and Saltman P: Low-level oxidative stress causes cell-cycle specific arrest in cultured cells. Biochem Biophys Res Commun. 210:189–196. 1995. View Article : Google Scholar : PubMed/NCBI
50	Knepper PA, Goossens W and Palmberg PF: Glycosaminoglycan stratification of the juxtacanalicular tissue in normal and primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 37:2414–2425. 1996.PubMed/NCBI
51	Knepper PA, Goossens W, Hvizd M and Palmberg PF: Glycosaminoglycans of the human trabecular meshwork in primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 37:1360–1367. 1996.PubMed/NCBI
52	Izzotti A, Longobardi M, Cartiglia C and Saccà SC: Mitochondrial damage in the trabecular meshwork occurs only in primary open-angle glaucoma and in pseudoexfoliative glaucoma. PLoS One. 6:e145672011. View Article : Google Scholar : PubMed/NCBI
53	Alvarado JA, Alvarado RG, Yeh RF, Franse-Carman L, Marcellino GR and Brownstein MJ: A new insight into the cellular regulation of aqueous outflow: How trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm's canal endothelial cells. Br J Ophthalmol. 89:1500–1505. 2005. View Article : Google Scholar : PubMed/NCBI
54	Zhou L, Li Y and Yue BY: Oxidative stress affects cytoskeletal structure and cell-matrix interactions in cells from an ocular tissue: The trabecular meshwork. J Cell Physiol. 180:182–189. 1999. View Article : Google Scholar : PubMed/NCBI
55	Giancotti FG: Integrin signaling: Specificity and control of cell survival and cell cycle progression. Curr Opin Cell Biol. 9:691–700. 1997. View Article : Google Scholar : PubMed/NCBI
56	Welge-Lüssen U and Birke K: Oxidative stress in the trabecular meshwork of POAG. Klin Monbl Augenheilkd. 227:99–107. 2010.In German.
57	Li G, Luna C, Liton PB, Navarro I, Epstein DL and Gonzalez P: Sustained stress response after oxidative stress in trabecular meshwork cells. Mol Vis. 13:2282–2288. 2007.
58	Dröge W: Free radicals in the physiological control of cell function. Physiol Rev. 82:47–95. 2002. View Article : Google Scholar : PubMed/NCBI
59	Frisch SM and Ruoslahti E: Integrins and anoikis. Curr Opin Cell Biol. 9:701–706. 1997. View Article : Google Scholar : PubMed/NCBI
60	Martindale JL and Holbrook NJ: Cellular response to oxidative stress: Signaling for suicide and survival. J Cell Physiol. 192:1–15. 2002. View Article : Google Scholar : PubMed/NCBI
61	Yan DB, Trope GE, Ethier CR, Menon IA and Wakeham A: Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes. Invest Ophthalmol Vis Sci. 32:2515–2520. 1991.PubMed/NCBI
62	Padgaonkar V, Giblin FJ, Leverenz V, Lin LR and Reddy VN: Studies of H₂O₂-induced effects on cultured bovine trabecular meshwork cells. J Glaucoma. 3:123–131. 1994. View Article : Google Scholar : PubMed/NCBI
63	De La Paz MA and Epstein DL: Effect of age on superoxide dismutase activity of human trabecular meshwork. Invest Ophthalmol Vis Sci. 37:1849–1853. 1996.PubMed/NCBI
64	Alvarado J, Murphy C, Polansky J and Juster R: Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci. 21:714–727. 1981.PubMed/NCBI
65	Freedman SF, Anderson PJ and Epstein DL: Superoxide dismutase and catalase of calf trabecular meshwork. Invest Ophthalmol Vis Sci. 26:1330–1335. 1985.PubMed/NCBI
66	Tan JC, Peters DM and Kaufman PL: Recent developments in understanding the pathophysiology of elevated intraocular pressure. Curr Opin Ophthalmol. 17:168–174. 2006.PubMed/NCBI
67	Gabelt BT and Kaufman PL: Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res. 24:612–637. 2005. View Article : Google Scholar : PubMed/NCBI
68	Kumar DM and Agarwal N: Oxidative stress in glaucoma: A burden of evidence. J Glaucoma. 16:334–343. 2007. View Article : Google Scholar : PubMed/NCBI
69	Izzotti A, Saccà SC, Cartiglia C and De Flora S: Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients. Am J Med. 114:638–646. 2003. View Article : Google Scholar : PubMed/NCBI
70	Saccà SC, Pascotto A, Camicione P, Capris P and Izzotti A: Oxidative DNA damage in the human trabecular meshwork: Clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol. 123:458–463. 2005. View Article : Google Scholar : PubMed/NCBI
71	Zanon-Moreno V, Marco-Ventura P, Lleo-Perez A, Pons-Vazquez S, Garcia-Medina JJ, Vinuesa-Silva I, Moreno-Nadal MA and Pinazo-Duran MD: Oxidative stress in primary open-angle glaucoma. J Glaucoma. 17:263–268. 2008. View Article : Google Scholar : PubMed/NCBI
72	Nguyen KP, Chung ML, Anderson PJ, Johnson M and Epstein DL: Hydrogen peroxide removal by the calf aqueous outflow pathway. Invest Ophthalmol Vis Sci. 29:976–981. 1988.PubMed/NCBI
73	Chen Y, Mehta G and Vasiliou V: Antioxidant defenses in the ocular surface. Ocul Surf. 7:176–185. 2009. View Article : Google Scholar : PubMed/NCBI
74	Behndig A, Svensson B, Marklund SL and Karlsson K: Superoxide dismutase isoenzymes in the human eye. Invest Ophthalmol Vis Sci. 39:471–475. 1998.PubMed/NCBI
75	Reiss GR, Werness PG, Zollman PE and Brubaker RF: Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals. Arch Ophthalmol. 104:753–755. 1986. View Article : Google Scholar : PubMed/NCBI
76	Tamm ER, Russell P, Johnson DH and Piatigorsky J: Human and monkey trabecular meshwork accumulate alpha B-crystallin in response to heat shock and oxidative stress. Invest Ophthalmol Vis Sci. 37:2402–2413. 1996.PubMed/NCBI
77	Hanashima C and Namiki H: Reduced viability of vascular endothelial cells by high concentration of ascorbic acid in vitreous humor. Cell Biol Int. 23:287–298. 1999. View Article : Google Scholar : PubMed/NCBI
78	Brubaker RF, Bourne WM, Bachman LA and McLaren JW: Ascorbic acid content of human corneal epithelium. Invest Ophthalmol Vis Sci. 41:1681–1683. 2000.PubMed/NCBI
79	Dreyer R and Rose RC: Lacrimal gland uptake and metabolism of ascorbic acid. Proc Soc Exp Biol Med. 202:212–216. 1993. View Article : Google Scholar : PubMed/NCBI
80	Becker B: Chemical composition of human aqueous humor; effects of acetazoleamide. AMA Arch Opthalmol. 57:793–800. 1957. View Article : Google Scholar
81	Giblin FJ, McCready JP, Kodama T and Reddy VN: A direct correlation between the levels of ascorbic acid and H₂O₂ in aqueous humor. Exp Eye Res. 38:87–93. 1984. View Article : Google Scholar : PubMed/NCBI
82	Ringvold A: The significance of ascorbate in the aqueous humour protection against UV-A and UV-B. Exp Eye Res. 62:261–264. 1996. View Article : Google Scholar : PubMed/NCBI
83	Griffiths HR and Lunec J: Ascorbic acid in the 21st century - more than a simple antioxidant. Environ Toxicol Pharmacol. 10:173–182. 2001. View Article : Google Scholar : PubMed/NCBI
84	Andorn AC, Britton RS and Bacon BR: Ascorbate-stimulated lipid peroxidation in human brain is dependent on iron but not on hydroxyl radical. J Neurochem. 67:717–722. 1996. View Article : Google Scholar : PubMed/NCBI
85	Song JH, Shin SH and Ross GM: Oxidative stress induced by ascorbate causes neuronal damage in an in vitro system. Brain Res. 895:66–72. 2001. View Article : Google Scholar : PubMed/NCBI
86	Lee SH, Oe T and Blair IA: Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science. 292:2083–2086. 2001. View Article : Google Scholar : PubMed/NCBI
87	Camougrand N and Rigoulet M: Aging and oxidative stress: Studies of some genes involved both in aging and in response to oxidative stress. Respir Physiol. 128:393–401. 2001. View Article : Google Scholar : PubMed/NCBI
88	Cejková J, Vejrazka M, Pláteník J and Stípek S: Age-related changes in superoxide dismutase, glutathione peroxidase, catalase and xanthine oxidoreductase/xanthine oxidase activities in the rabbit cornea. Exp Gerontol. 39:1537–1543. 2004. View Article : Google Scholar : PubMed/NCBI
89	Samiec PS, Drews-Botsch C, Flagg EW, Kurtz JC, Sternberg P Jr, Reed RL and Jones DP: Glutathione in human plasma: Decline in association with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med. 24:699–704. 1998. View Article : Google Scholar : PubMed/NCBI
90	Serbecic N and Beutelspacher SC: Vitamins inhibit oxidant-induced apoptosis of corneal endothelial cells. Jpn J Ophthalmol. 49:355–362. 2005. View Article : Google Scholar : PubMed/NCBI
91	Wallace DC: A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu Rev Genet. 39:359–407. 2005. View Article : Google Scholar : PubMed/NCBI
92	Gherghel D, Griffiths HR, Hilton EJ, Cunliffe IA and Hosking SL: Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 46:877–883. 2005. View Article : Google Scholar : PubMed/NCBI
93	Ferreira SM, Lerner SF, Brunzini R, Evelson PA and Llesuy SF: Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol. 137:62–69. 2004. View Article : Google Scholar : PubMed/NCBI
94	Ghanem AA, Arafa LF and El-Baz A: Oxidative stress markers in patients with primary open-angle glaucoma. Curr Eye Res. 35:295–301. 2010. View Article : Google Scholar : PubMed/NCBI
95	Yang J, Tezel G, Patil RV, Romano C and Wax MB: Serum autoantibody against glutathione S-transferase in patients with glaucoma. Invest Ophthalmol Vis Sci. 42:1273–1276. 2001.PubMed/NCBI
96	Bagnis A, Izzotti A, Centofanti M and Saccà SC: Aqueous humor oxidative stress proteomic levels in primary open angle glaucoma. Exp Eye Res. 103:55–62. 2012. View Article : Google Scholar : PubMed/NCBI
97	Majsterek I, Malinowska K, Stanczyk M, Kowalski M, Blaszczyk J, Kurowska AK, Kaminska A, Szaflik J and Szaflik JP: Evaluation of oxidative stress markers in pathogenesis of primary open-angle glaucoma. Exp Mol Pathol. 90:231–237. 2011. View Article : Google Scholar : PubMed/NCBI
98	Famili A, Ammar DA and Kahook MY: Ethyl pyruvate treatment mitigates oxidative stress damage in cultured trabecular meshwork cells. Mol Vis. 19:1304–1309. 2013.PubMed/NCBI
99	Ammar DA, Hamweyah KM and Kahook MY: Antioxidants protect trabecular meshwork cells from hydrogen peroxide-induced cell death. Transl Vis Sci Technol. 1:42012. View Article : Google Scholar : PubMed/NCBI
100	Yu AL, Fuchshofer R, Kampik A and Welge-Lüssen U: Effects of oxidative stress in trabecular meshwork cells are reduced by prostaglandin analogues. Invest Ophthalmol Vis Sci. 49:4872–4880. 2008. View Article : Google Scholar : PubMed/NCBI
101	Yang Y, Liu X, Huang J, Zhong Y, Mao Z, Xiao H, Li M and Zhuo Y: Inhibition of p38 mitogen-activated protein kinase phosphorylation decrease tert-butyl hydroperoxide-induced apoptosis in human trabecular meshwork cells. Mol Vis. 18:2127–2136. 2012.PubMed/NCBI
102	Awai-Kasaoka N, Inoue T, Kameda T, Fujimoto T, Inoue-Mochita M and Tanihara H: Oxidative stress response signaling pathways in trabecular meshwork cells and their effects on cell viability. Mol Vis. 19:1332–1340. 2013.PubMed/NCBI
103	Tourtas T, Birke MT, Kruse FE, Welge-Lüssen UC and Birke K: Preventive effects of omega-3 and omega-6 fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells. PLoS One. 7:e313402012. View Article : Google Scholar : PubMed/NCBI
104	Ham WT Jr, Mueller HA, Ruffolo JJ Jr, Millen JE, Cleary SF, Guerry RK and Guerry D III: Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr Eye Res. 3:165–174. 1984. View Article : Google Scholar : PubMed/NCBI
105	Yokoyama Y, Maruyama K, Yamamoto K, Omodaka K, Yasuda M, Himori N, Ryu M, Nishiguchi KM and Nakazawa T: The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage. Biochem Biophys Res Commun. 451:510–515. 2014. View Article : Google Scholar : PubMed/NCBI
106	Liu Q, Wu K, Qiu X, Yang Y, Lin X and Yu M: siRNA silencing of gene expression in trabecular meshwork: RhoA siRNA reduces IOP in mice. Curr Mol Med. 12:1015–1027. 2012. View Article : Google Scholar : PubMed/NCBI
107	Romagnolo DF and Selmin OI: Flavonoids and cancer prevention: A review of the evidence. J Nutr Gerontol Geriatr. 31:206–238. 2012. View Article : Google Scholar : PubMed/NCBI
108	Miller KB, Stuart DA, Smith NL, Lee CY, McHale NL, Flanagan JA, Ou B and Hurst WJ: Antioxidant activity and polyphenol and procyanidin contents of selected commercially available cocoa-containing and chocolate products in the United States. J Agric Food Chem. 54:4062–4068. 2006. View Article : Google Scholar : PubMed/NCBI
109	Haufschild T, Kaiser HJ, Preisig T, Pruente C and Flammer J: Influence of red wine on visual function and endothelin-1 plasma level in a patient with optic neuritis. Ann Neurol. 53:825–826. 2003. View Article : Google Scholar : PubMed/NCBI
110	Määttä-Riihinen KR, Kähkönen MP, Törrönen AR and Heinonen IM: Catechins and procyanidins in berries of vaccinium species and their antioxidant activity. J Agric Food Chem. 53:8485–8491. 2005. View Article : Google Scholar : PubMed/NCBI
111	Cybulska-Heinrich A, Mozaffarieh M and Flammer J: Value of non-IOP lowering therapy for glaucoma. Klin Monbl Augenheilkd. 230:114–119. 2013.In German. PubMed/NCBI
112	Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P and Gonzalez P: Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol. 47:198–204. 2009. View Article : Google Scholar :
113	Zanon-Moreno V, Garcia-Medina JJ, Gallego-Pinazo R, Vinuesa-Silva I, Moreno-Nadal MA and Pinazo-Duran MD: Antioxidant status modifications by topical administration of dorzolamide in primary open-angle glaucoma. Eur J Ophthalmol. 19:565–571. 2009.PubMed/NCBI
114	Gutteridge JM and Halliwell B: Antioxidants: Molecules, medicines, and myths. Biochem Biophys Res Commun. 393:561–564. 2010. View Article : Google Scholar : PubMed/NCBI
115	Bjelakovic G, Nikolova D, Simonetti RG and Gluud C: Antioxidant supplements for prevention of gastrointestinal cancers: A systematic review and meta-analysis. Lancet. 364:1219–1228. 2004. View Article : Google Scholar : PubMed/NCBI
116	Talaulikar VS and Manyonda IT: Vitamin C as an antioxidant supplement in women's health: A myth in need of urgent burial. Eur J Obstet Gynecol Reprod Biol. 157:10–13. 2011. View Article : Google Scholar : PubMed/NCBI
117	Kaisar MA and Cucullo L: OTC antioxidant products for the treatment of cardiovascular and other disorders: Popular myth or fact? J Pharmacovigil. 3:e1362015. View Article : Google Scholar : PubMed/NCBI
118	Garcia-Medina JJ, Garcia-Medina M, Garrido-Fernandez P, Galvan-Espinosa J, Garcia-Maturana C, Zanon-Moreno V and Pinazo-Duran MD: A two-year follow-up of oral antioxidant supplementation in primary open-angle glaucoma: An open-label, randomized, controlled trial. Acta Ophthalmol. 93:546–554. 2015. View Article : Google Scholar
119	Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ and Morrison SJ: Oxidative stress inhibits distant metastasis by human melanoma cells. Nature. 527:186–191. 2015. View Article : Google Scholar : PubMed/NCBI