Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown.

Laboratory of Eye Histochemistry and Pharmacology Department of Neuroscience Institute of Experimental Medicine Academy of Sciences of the Czech Republic Vídeňská 1083 14220 Prague 4 Czech Republic

Zobrazit více v PubMed

Wakamatsu T. H., Dogru M., Ayako I., et al. Evaluation of lipid oxidative stress status and inflammation in topic ocular surface disease. Molecular Vision. 2010;19(16):2465–2475. PubMed PMC

Spector A. Oxidative stress-induced cataract: mechanism of action. The FASEB Journal. 1995;9(12):1173–1182. PubMed

Yadav U. C. S., Kalariya N. M., Ramana K. V. Emerging role of antioxidants in the protection of uveitis complications. Current Medicinal Chemistry. 2011;18(6):931–942. doi: 10.2174/092986711794927694. PubMed DOI PMC

Ishimoto S. I., Wu G. S., Hayashi S., Zhang J., Rao N. A. Free radical tissue damages in the anterior segment of the eye in experimental autoimmune uveitis. Investigative Ophthalmology and Visual Science. 1996;37(4):630–636. PubMed

Gritz D. C., Montes C., Atalla L. R., Wu G.-S., Sevanian A., Rao N. A. Histochemical localization of superoxide production in experimental autoimmune uveitis. Current Eye Research. 1991;10(10):927–931. doi: 10.3109/02713689109020328. PubMed DOI

Niesman M. R., Johnson K. A., Penn J. S. Therapeutic effect of liposomal superoxide dismutase in an animal model of retinopathy of prematurity. Neurochemical Research. 1997;22(5):597–605. doi: 10.1023/A:1022474120512. PubMed DOI

Wilkinson-Berka J. L., Rana I., Armani R., Agrotis A. Reactive oxygen species, Nox and angiotensin II in angiogenesis: implications for retinopathy. Clinical Science. 2013;124(10):597–615. doi: 10.1042/cs20120212. PubMed DOI

Chiras D., Kitsos G., Petersen M. B., Skalidakis I., Kroupis C. Oxidative stress in dry age-related macular degeneration and exfoliation syndrome. Critical Reviews in Clinical Laboratory Sciences. 2015;52(1):12–27. doi: 10.3109/10408363.2014.968703. PubMed DOI

Ammar D. A., Hamweyah K. M., Kahook M. Y. Antioxidants protect Trabecular meshwork Cells from hydrogen peroxide-induced cell death. Translational Vision Science & Technology. 2012;1(1):4–8. doi: 10.1167/tvst.1.1.4. PubMed DOI PMC

Aslan M., Dogan S., Kucuksayan E. Oxidative stress and potential applications of free radical scavengers in glaucoma. Redox Report. 2013;18(2):76–87. doi: 10.1179/1351000212y.0000000033. PubMed DOI PMC

Pinazo-Durán M. D., Zanón-Moreno V., García-Medina J. J., Gallego-Pinazo R. Evaluation of presumptive biomarkers of oxidative stress, immune response and apoptosis in primary open-angle glaucoma. Current Opinion in Pharmacology. 2013;13(1):98–107. doi: 10.1016/j.coph.2012.10.007. PubMed DOI

Alio J. L., Ayala M. J., Mulet M. E., Artola A., Ruiz J. M., Bellot J. Antioxidant therapy in the treatment of experimental acute corneal inflammation. Ophthalmic Research. 1995;27(3):136–143. PubMed

Augustin A. J., Spitznas M., Kaviani N., et al. Oxidative reactions in the tear fluid of patients suffering from dry eyes. Graefe's Archive for Clinical and Experimental Ophthalmology. 1995;233(11):694–698. doi: 10.1007/BF00164671. PubMed DOI

Čejková J., Ardan T., Šimonová Z., et al. Nitric oxide synthase induction and cytotoxic nitrogen-related oxidant formation in conjunctival epithelium of dry eye (Sjögren's syndrome) Nitric Oxide—Biology and Chemistry. 2007;17(1):10–17. doi: 10.1016/j.niox.2007.04.006. PubMed DOI

Čejková J., Ardan T., Šimonová Z., et al. Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjögren's syndrome) and its possible contribution to the development of ocular surface oxidative injuries. Histology and Histopathology. 2008;23(12):1477–1483. PubMed

Čejková J., Ardan T., Čejka Č., et al. Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness. Histology and Histopathology. 2009;24(10):1357–1365. PubMed

Arnal E., Peris-Martínez C., Menezo J. L., Johnsen-Soriano S., Romero F. J. Oxidative stress in keratoconus? Investigative Ophthalmology and Visual Science. 2011;52(12):8592–8597. doi: 10.1167/iovs.11-7732. PubMed DOI

Buddi R., Lin B., Atilano S. R., Zorapapel N. C., Kenney M. C., Brown D. J. Evidence of oxidative stress in human corneal diseases. Journal of Histochemistry and Cytochemistry. 2002;50(3):341–351. doi: 10.1177/002215540205000306. PubMed DOI

Čejková J., Ardan T., Čejka Č., Kovačeva J., Zídek Z. Irradiation of the rabbit cornea with UVB rays stimulates the expression of nitric oxide synthase-generated nitric oxide and the formation of cytotoxic nitrogen-related oxidants. Histology and Histopathology. 2005;20(2):467–473. PubMed

Čejková J., Štípek S., Crkovská J., et al. UV rays, the prooxidant / antioxidant imbalance in the cornea and oxidative eye damage. Physiological Research. 2004;53(1):1–10. PubMed

Zhou T., Zong R., Zhang Z., et al. SERPINA3K protects against oxidative stress via modulating ROS generation/degradation and KEAP1-NRF2 pathway in the corneal epithelium. Investigative Ophthalmology and Visual Science. 2012;53(8):5033–5043. doi: 10.1167/iovs.12-9729. PubMed DOI

Čejka Č., Pláteník J., Guryca V., et al. Light absorption properties of the rabbit cornea repeatedly irradiated with UVB rays. Photochemistry and Photobiology. 2007;83(3):652–657. doi: 10.1111/j.1751-1097.2007.00061.x. PubMed DOI

Eaton J. W. UV-mediated cataractogenesis: a radical perspective. Documenta Ophthalmologica. 1994;88(3):233–242. doi: 10.1007/bf01203677. PubMed DOI

Mitchell J., Cenedella R. J. Quantitation of ultraviolet light-absorbing fractions of the cornea. Cornea. 1995;14(3):266–272. doi: 10.1097/00003226-199505000-00007. PubMed DOI

Kolozsvári L., Nógrádi A., Hopp B., Bor Z. UV absorbance of the human cornea in the 240- to 400-nm range. Investigative Ophthalmology and Visual Science. 2002;43(7):2165–2168. PubMed

Podskochy A. Protective role of corneal epithelium against ultraviolet radiation damage. Acta Ophthalmologica Scandinavica. 2004;82(6):714–717. doi: 10.1111/j.1600-0420.2004.00369.x. PubMed DOI

Ringvold A. The significance of ascorbate in the aqueous humour protection against UV-A and UV-B. Experimental Eye Research. 1996;62(3):261–264. doi: 10.1006/exer.1996.0031. PubMed DOI

Ringvold A. In vitro evidence for UV-protection of the eye by the corneal epithelium mediated by the cytoplasmic protein, RNA, and ascorbate. Acta Ophthalmologica Scandinavica. 1997;75(5):496–498. PubMed

Brubaker R. F., Bourne W. M., Bachman L. A., McLaren J. W. Ascorbic acid content of human corneal epithelium. Investigative Ophthalmology and Visual Science. 2000;41(7):1681–1683. PubMed

Bilgihan A., Bilgihan K., Toklu Y., Konuk O., Yis Ö., Hasanreisoğlu B. Ascorbic acid levels in human tears after photorefractive keratectomy, transepithelial photorefractive keratectomy, and laser in situ keratomileusis. Journal of Cataract and Refractive Surgery. 2001;27(4):585–588. doi: 10.1016/s0886-3350(00)00877-4. PubMed DOI

Bilgihan A., Bilgihan K., Yis Ö., Sezer C., Akyol G., Hasanreisoglu B. Effects of topical vitamin E on corneal superoxide dismutase, glutathione peroxidase activities and polymorphonuclear leucocyte infiltration after photorefractive keratectomy. Acta Ophthalmologica Scandinavica. 2003;81(2):177–180. doi: 10.1034/j.1600-0420.2003.00042.x. PubMed DOI

Atalla L. R., Sevanian A., Rao N. A. Immunohistochemical localization of glutathione peroxidase in ocular tissue. Current Eye Research. 1988;7(10):1023–1027. doi: 10.3109/02713688809015149. PubMed DOI

Abedinia M., Pain T., Algar E. M., Holmes R. S. Bovine corneal aldehyde dehydrogenase: the major soluble corneal protein with a possible dual protective role for the eye. Experimental Eye Research. 1990;51(4):419–426. doi: 10.1016/0014-4835(90)90154-m. PubMed DOI

Downes J. E., VandeBerg J. L., Hubbard G. B., Holmes R. S. Regional distribution of mammalian corneal aldehyde dehydrogenase and alcohol dehydrogenase. Cornea. 1992;11(6):560–566. doi: 10.1097/00003226-199211000-00013. PubMed DOI

Uma L., Hariharan J., Sharma Y., Balasubramanian D. Effect of UVB radiation on corneal aldehyde dehydrogenase. Current Eye Research. 1996;15(6):685–690. doi: 10.3109/02713689609008910. PubMed DOI

Piatigorsky J. Enigma of the abundant water-soluble cytoplasmic proteins of the cornea: the “refracton” hypothesis. Cornea. 2001;20(8):853–858. doi: 10.1097/00003226-200111000-00015. PubMed DOI

Young A. R. Acute effects of UVR on human eyes and skin. Progress in Biophysics and Molecular Biology. 2006;92(6):80–85. PubMed

Cullen A. P. Photokeratitis and other phototoxic effects on the cornea and conjunctiva. International Journal of Toxicology. 2002;21(6):455–464. doi: 10.1080/10915810290169882. PubMed DOI

Pitts D. G., Cullen A. P., Hacker P. D. Ocular effects of ultraviolet radiation from 295 to 365 nm. Investigative Ophthalmology and Visual Science. 1977;16(10):932–939. PubMed

Doughty M. J., Cullen A. P. Long-term effects of a single dose of ultraviolet-B on albino rabbit cornea—II. Deturgescence and fluid pump assessed in vitro. Photochemistry and photobiology. 1990;51(4):439–449. doi: 10.1111/j.1751-1097.1990.tb01735.x. PubMed DOI

Čejka Č., Pláteník J., Buchal R., et al. Effect of two different UVA doses on the rabbit cornea and lens. Photochemistry and Photobiology. 2009;85(3):794–800. doi: 10.1111/j.1751-1097.2008.00478.x. PubMed DOI

Rogers C. S., Chan L.-M., Sims Y. S., Byrd K. D., Hinton D. L., Twining S. S. The effects of sub-solar levels of UV-A and UV-B on rabbit corneal and lens epithelial cells. Experimental Eye Research. 2004;78(5):1007–1014. doi: 10.1016/j.exer.2003.12.011. PubMed DOI

Podskochy A., Gan L., Fagerholm P. Apoptosis in UV-exposed rabbit corneas. Cornea. 2000;19(1):99–103. doi: 10.1097/00003226-200001000-00019. PubMed DOI

Kennedy M., Kim K. H., Harten B., et al. Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells. Investigative Ophthalmology and Visual Science. 1997;38(12):2483–2491. PubMed

Hong J.-W., Liu J. J., Lee J.-S., et al. Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea. Investigative Ophthalmology and Visual Science. 2001;42(12):2795–2803. PubMed

Čejková J., Štípek S., Crkovská J., Ardan T., Midelfart A. Reactive oxygen species (ROS)-generating oxidases in the normal rabbit cornea and their involvement in the corneal damage evoked by UVB rays. Histology and Histopathology. 2001;16(2):523–533. PubMed

Cejkova J., Stipek S., Crkovska J., Ardan T. Changes of antioxidant enzymes in the cornea of albino rabbits irradiated with UVB rays. Histochemical and biochemical study. Histology and Histopathology. 2000;15(4):1043–1050. PubMed

Lodovici M., Caldini S., Morbidelli L., Akpan V., Ziche M., Dolara P. Protective effect of 4-coumaric acid from UVB ray damage in the rabbit eye. Toxicology. 2009;255(1-2):1–5. doi: 10.1016/j.tox.2008.09.011. PubMed DOI

Downes J. E., Swann P. G., Holmes R. S. Ultraviolet light-induced pathology in the eye: associated changes in ocular aldehyde dehydrogenase and alcohol dehydrogenase activities. Cornea. 1993;12(3):241–248. doi: 10.1097/00003226-199305000-00010. PubMed DOI

Tessem M.-B., Bathen T. F., Čejková J., Midelfart A. Effect of UV-A and UV-B irradiation on the metabolic profile of aqueous humor in rabbits analyzed by 1H NMR spectroscopy. Investigative Ophthalmology and Visual Science. 2005;46(3):776–781. doi: 10.1167/iovs.04-0787. PubMed DOI

Tessem M.-B., Midelfart A., Čejková J., Bathen T. F. Effect of UVA and UVB irradiation on the metabolic profile of rabbit cornea and lens analysed by HR-MAS H NMR spectroscopy. Ophthalmic Research. 2006;38(2):105–114. doi: 10.1159/000090511. PubMed DOI

Čejková J., Čejka C., Ardan T., Širc J., Michálek J., Luyckx J. Reduced UVB-induced corneal damage caused by reactive oxygen and nitrogen species and decreased changes in corneal optics after trehalose treatment. Histology and Histopathology. 2010;25(11):1403–1416. PubMed

Čejková J., Ardan T., Čejka Č., Luyckx J. Favorable effects of trehalose on the development of UVB-mediated antioxidant/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression. Graefe's Archive for Clinical and Experimental Ophthalmology. 2011;249(8):1185–1194. doi: 10.1007/s00417-011-1676-y. PubMed DOI

Čejková J., Čejka Č., Luyckx J. Trehalose treatment accelerates the healing of UVB-irradiated corneas. Comparative immunohistochemical studies on corneal cryostat sections and corneal impression cytology. Histology and Histopathology. 2012;27(8):1029–1040. PubMed

Pauloin T., Dutot M., Joly F., Warnet J.-M., Rat P. High molecular weight hyaluronan decreases UVB-induced apoptosis and inflammation in human epithelial corneal cells. Molecular Vision. 2009;15:577–583. PubMed PMC

Li J.-M., Chou H.-C., Wang S.-H., et al. Hyaluronic acid-dependent protection against UVB-damaged human corneal cells. Environmental and Molecular Mutagenesis. 2013;54(6):429–449. doi: 10.1002/em.21794. PubMed DOI

Čejka Č., Ardan T., Širc J., Michálek J., Brůnová B., Čejková J. The influence of various toxic effects on the cornea and changes in corneal light transmission. Graefe's Archive for Clinical and Experimental Ophthalmology. 2010;248(12):1749–1756. doi: 10.1007/s00417-010-1438-2. PubMed DOI

Randleman J. B., Loft E. S. Ophthalmologic Approach to Chemical Burns. 2014. http://emedicine.medscape.com/article/1215950-overview.

Meek K. M., Dennis S., Khan S. Changes in the refractive index of the stroma and its extrafibrillar matrix when the cornea swells. Biophysical Journal. 2003;85(4):2205–2212. doi: 10.1016/S0006-3495(03)74646-3. PubMed DOI PMC

Kim Y. L., Walsh J. T., Jr., Goldstick T. K., Glucksberg M. R. Variation of corneal refractive index with hydration. Physics in Medicine and Biology. 2004;49(5):859–868. doi: 10.1088/0031-9155/49/5/015. PubMed DOI

Patel S., Marshall J., Fitzke F. W., III Refractive index of the human corneal epithelium and stroma. Journal of Refractive Surgery. 1995;11(2):100–105. PubMed

Kubota M., Shimmura S., Kubota S., et al. Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Investigative Ophthalmology and Visual Science. 2011;52(1):427–433. doi: 10.1167/iovs.10-6167. PubMed DOI

Cejkova J., Trosan P., Cejka C., et al. Suppression of alkali-induced oxidative injury in the cornea by mesenchymal stem cells growing on nanofiber scaffolds and transferred onto the damaged corneal surface. Experimental Eye Research. 2013;116(2):312–323. doi: 10.1016/j.exer.2013.10.002. PubMed DOI

Javorkova E., Trosan P., Zajicova A., et al. Modulation of the early inflammatory microenvironment in the alkali-burned eye by systemically administered interferon-γ-treated mesenchymal stromal cells. Stem Cells and Development. 2014;23(20):2490–2500. doi: 10.1089/scd.2013.0568. PubMed DOI PMC

Yao L., Li Z.-R., Su W.-R., et al. Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn. PLoS ONE. 2012;7(2) doi: 10.1371/journal.pone.0030842.e30842 PubMed DOI PMC

Brignole F., Potron L., Martin C., et al. Effects of RTGA OTR4131 on ocular surface: in vivo evaluation on a rabbit corneal wound healing model and in vitro toxicological studies. Investigative Ophthalmology and Visual Sciences. 2005;46, E-Abstract 2166

Garcia-Filipe S., Barbier-Chassefiere V., Alexakis C., et al. RGTA OTR4120, a heparan sulfate mimetic, is a possible long-term active agent to heal burned skin. Journal of Biomedical Materials Research—Part A. 2007;80(1):75–84. doi: 10.1002/jbm.a.30874. PubMed DOI

Cejkova J., Olmiere C., Cejka C., Trosan P., Holan V. The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage. Histology and Histopathology. 2014;29(4):457–478. PubMed

Brignole-Baudouin F., Warnet J. M., Barritault D., Baudouin C. RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies. Journal Francais d'Ophtalmologie. 2013;36(9):740–747. doi: 10.1016/j.jfo.2013.01.012. PubMed DOI

Aifa A., Gueudry J., Portmann A., Delcampe A., Muraine M. Topical treatment with a new matrix therapy agent (RGTA) for the treatment of corneal neurotrophic ulcers. Investigative Ophthalmology and Visual Science. 2012;53(13):8181–8185. doi: 10.1167/iovs.12-10476. PubMed DOI

Pfister R. R., Haddox J. L., Yuille-Barr D. The combined effect of citrate/ascorbate treatment in alkali-injured rabbit eyes. Cornea. 1991;10(2):100–104. doi: 10.1097/00003226-199103000-00002. PubMed DOI

Pfister R. R., Haddox J. L., Lank K. M. Citrate or ascorbate/citrate treatment of established corneal ulcers in the alkali-injured rabbit eye. Investigative Ophthalmology and Visual Science. 1988;29(7):1110–1115. PubMed

Macway-Jones K., Marsden J. Ascorbate for alkali burns to the eye. Emergency Medicine Journal. 2003;20(5):465–466. doi: 10.1136/emj.20.5.465. PubMed DOI PMC

Yang G., Espandar L., Mamalis N., Prestwich G. D. A cross-linked hyaluronan gel accelerates healing of corneal epithelial abrasion and alkali burn injuries in rabbits. Veterinary Ophthalmology. 2010;13(3):144–150. doi: 10.1111/j.1463-5224.2010.00771.x. PubMed DOI

Chung J. H., Kim H. J., Fagerholmb P., Cho B. C. Effect of topically applied Na-hyaluronan on experimental corneal alkali wound healing. Korean Journal of Ophthalmology. 1996;10(2):68–75. doi: 10.3341/kjo.1996.10.2.68. PubMed DOI

Chung J.-H., Fagerholm P., Lindstrom B. Hyaluronate in healing of corneal alkali wound in the rabbit. Experimental Eye Research. 1989;48(4):569–576. doi: 10.1016/0014-4835(89)90039-0. PubMed DOI

Sekundo W., Augustin A. J., Strempel I. Topical allopurinol or corticosteroids and acetylcysteine in the early treatment of experimental corneal alkali burns: a pilot study. European Journal of Ophthalmology. 2002;12(5):366–372. PubMed

Saud E. E., Moraes H. V., Jr., Marculino L. G. C., Gomes J. A. P., Allodi S., Miguel N. C. O. Clinical and histopathological outcomes of subconjunctival triamcinolone injection for the treatment of acute ocular alkali burn in rabbits. Cornea. 2012;31(2):181–187. doi: 10.1097/ico.0b013e318221ce99. PubMed DOI

Dan L., Shi-Long Y., Miao-Li L., et al. Inhibitory effect of oral doxycycline on neovascularization in a rat corneal alkali burn model of angiogenesis. Current Eye Research. 2008;33(8):653–660. doi: 10.1080/02713680802245772. PubMed DOI

Ling S., Li W., Liu L., et al. Allograft survival enhancement using doxycycline in alkali-burned mouse corneas. Acta Ophthalmologica. 2013;91(5):e369–e378. doi: 10.1111/aos.12070. PubMed DOI

Su W., Li Z., Li Y., et al. Doxycycline enhances the inhibitory effects of bevacizumab on corneal neovascularization and prevents its side effects. Investigative Ophthalmology and Visual Science. 2011;52(12):9108–9115. doi: 10.1167/iovs.11-7255. PubMed DOI

Shin Y. J., Hyon J. Y., Choi W. S., et al. Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-β1/ERK pathways regulation. Investigative Ophthalmology and Visual Science. 2013;54(7):4452–4458. doi: 10.1167/iovs.13-11684. PubMed DOI

Shahriari H. A., Famil Tokhmehchi M. R., Hashemi N. F. Comparison of the effect of amniotic membrane suspension and autologous serum on alkaline corneal epithelial wound healing in the rabbit model. Cornea. 2008;27(10):1148–1150. doi: 10.1097/ICO.0b013e318173138a. PubMed DOI

Oh H. J., Jang J. Y., Li Z., Park S. H., Yoon K. C. Effects of umbilical cornd serum eye drops in a mouse model of ocular chemical burn. Current Eye Research. 2012;37(12):1084–1090. doi: 10.3109/02713683.2012.717243. PubMed DOI

The Healing of Oxidative Injuries with Trehalose in UVB-Irradiated Rabbit Corneas