Skip to main content
SpringerLink
Log in

Oxidative Stress in Cornea

  • Chapter
  • First Online:
Studies on the Cornea and Lens

Abstract

Oxidative stress has been implicated in many pathophysiological events. A disturbance in the pro-oxidant and antioxidant balance leads to potential damage and corneal diseases. Oxidative stress has been reported to play an essential role in corneal normal physiology as well as corneal pathology. Reactive oxygen species are not only considered to be the damaging factors in various pathologies, but they also participate in a wide variety of physiological processes such as signaling transduction. In this chapter, the role of oxidative stress and antioxidants was described at the aspects of cellular damages, proliferation, and inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002;50:341–51.

    CAS  PubMed  Google Scholar 

  2. Freeman BA, Crapo JD. Biology of disease: free radicals and tissue injury. Lab Invest. 1982;47:412–26.

    CAS  PubMed  Google Scholar 

  3. Afanas’ev I. ROS and RNS signaling in heart disorders: could antioxidant treatment be successful? Oxid Med Cell Longev. 2011;2011:293769.

    PubMed Central  PubMed  Google Scholar 

  4. Bisbal C, Lambert K, Avignon A. Antioxidants and glucose metabolism disorders. Curr Opin Clin Nutr Metab Care. 2010;13(4):439–46.

    CAS  PubMed  Google Scholar 

  5. Crouch RK, Goletz P, Snyder A, Coles WH. Antioxidant enzymes in human tears. J Ocul Pharmacol. 1991;7(3):253–8.

    CAS  PubMed  Google Scholar 

  6. Gogia R, Richer SP, Rose RC. Tear fluid content of electrochemically active components including water soluble antioxidants. Curr Eye Res. 1998;17(3):257–63.

    CAS  PubMed  Google Scholar 

  7. Shoham A, Hadziahmetovic M, Dunaief JL, Mydlarski MB, Schipper HM. Oxidative stress in diseases of the human cornea. Free Radic Biol Med. 2008;45(8):1047–55.

    CAS  PubMed  Google Scholar 

  8. Williams RN, Paterson CA. The influence of topical corticosteroid therapy upon polymorphonuclear leukocyte distribution, vascular integrity and ascorbate levels in endotoxin-induced inflammation of the rabbit eye. Exp Eye Res. 1987;44(2):191–8.

    CAS  PubMed  Google Scholar 

  9. Maurice DM. The structure and transparency of the cornea. J Physiol (Lond). 1957;136:263–86.

    CAS  Google Scholar 

  10. Dikstein S, Maurice DM. The active control of corneal hydration. Isr J Med Sci. 1972;8:1523–8.

    CAS  PubMed  Google Scholar 

  11. Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47:1239–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Gillespie MN, Pastukh V, Ruchko MV. Oxidative DNA modifications in hypoxic signaling. Ann N Y Acad Sci. 2009;1177:140–50.

    CAS  PubMed  Google Scholar 

  13. Shin YJ, Cho DY, Chung TY, Han SB, Hyon JY, Wee WR. Rapamycin reduces reactive oxygen species in cultured human corneal endothelial cells. Curr Eye Res. 2011;36(12):1116–22.

    CAS  PubMed  Google Scholar 

  14. Loh KP, Huang SH, De Silva R, Tan BK, Zhu YZ. Oxidative stress: apoptosis in neuronal injury. Curr Alzheimer Res. 2006;3:327–37.

    Google Scholar 

  15. Nishi Y, Engler C, Na DR, Kashiwabuchi RT, Shin YJ, Cano M, Jun AS, Chuck RS. Evaluation of phacoemulsification-induced oxidative stress and damage of cultured human corneal endothelial cells in different solutions using redox fluorometry microscopy. Acta Ophthalmol. 2010;88(8):e323–7.

    PubMed  Google Scholar 

  16. Shin YJ, Nishi Y, Engler C, Kang J, Hashmi S, Jun AS, Gehlbach PL, Chuck RS. The effect of phacoemulsification energy on the redox state of cultured human corneal endothelial cells. Arch Ophthalmol. 2009;127:435–41.

    CAS  PubMed  Google Scholar 

  17. Augustin AJ, Dick HB. Oxidative tissue damage after phacoemulsification: influence of ophthalmic viscosurgical devices. J Cataract Refract Surg. 2004;30:424–7.

    PubMed  Google Scholar 

  18. Shin YJ, Tata DB, Waynant RE, Gehlbach PL, Chuck RS. Fluorometric determination of the redox state and distribution of mitochondria in human malignant glioblastoma cells grown on different culturing substrates. Photomed Laser Surg. 2010;28 Suppl 1:S105–10.

    CAS  PubMed  Google Scholar 

  19. del V Cano M, Reyes JM, Park CY, et al. Demonstration by redox fluorometry that sulforaphane protects retinal pigment epithelial cells against oxidative stress. Invest Ophthalmol Vis Sci. 2008;49(6):2606–12.

    PubMed  Google Scholar 

  20. Huang S, Heikal AA, Webb WW. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys J. 2002;82(5):2811–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Shimmura S, Tsubota K, Oguchi Y, Fukumura D, Suematsu M, Tsuchiya M. Oxiradical-dependent photoemission induced by a phacoemulsification probe. Invest Ophthalmol Vis Sci. 1992;33(10):2904–7.

    CAS  PubMed  Google Scholar 

  22. Holst A, Rolfsen W, Svensson B, Ollinger K, Lundgren B. Formation of free radicals during phacoemulsification. Curr Eye Res. 1993;12(4):359–65.

    CAS  PubMed  Google Scholar 

  23. Cameron MD, Poyer JF, Aust SD. Identification of free radicals produced during phacoemulsification. J Cataract Refract Surg. 2001;27(3):463–70.

    CAS  PubMed  Google Scholar 

  24. Takahashi H, Sakamoto A, Takahashi R, Ohmura T, Shimmura S, Ohara K. Free radicals in phacoemulsification and aspiration procedures. Arch Ophthalmol. 2002;120(10):1348–52.

    PubMed  Google Scholar 

  25. Ricci JE, Gottlieb RA, Green DR. Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. J Cell Biol. 2003;160(1):65–75.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Fleury C, Mignotte B, Vayssière JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie. 2002;84(2–3):131–41.

    CAS  PubMed  Google Scholar 

  27. Finger PT. Radiation therapy for orbital tumors: concepts, current use, and ophthalmic radiation side effects. Surv Ophthalmol. 2009;54:545–68.

    PubMed  Google Scholar 

  28. Kiuchi T, Tatsuzaki H, Wakabayashi T, Okamoto F, Kaji Y, Oshika T. Long-term changes in rabbit cornea after ionizing radiation. Cornea. 2004;23:S87–90.

    PubMed  Google Scholar 

  29. Kiuchi T, Tatsuzaki H, Hommura S, Oshika T. Specular microscopic study of X-ray-irradiated rabbit cornea. Eye (Lond). 2004;18:929–34.

    CAS  Google Scholar 

  30. Blodi FC. The effects of experimental x-radiation on the cornea. Arch Ophthalmol. 1960;63:20–9.

    CAS  PubMed  Google Scholar 

  31. Jooyandeh F, Moore JS, Morgan RE, Phillips GO. Chemical effects of gamma-irradiation of aqueous solutions of heparin and keratan sulphate. Radiat Res. 1971;45:455–61.

    CAS  PubMed  Google Scholar 

  32. Beutel J, Schroder C, von Hof K, Kosmehl H, Wedel T, Sieg P, et al. Pharmacological prevention of radiation-induced dry eye-an experimental study in a rabbit model. Graefes Arch Clin Exp Ophthalmol. 2007;245:1347–55.

    CAS  PubMed  Google Scholar 

  33. Fard-Esfahani A, Mirshekarpour H, Fallahi B, Eftekhari M, Ekhari M, Saghari M, et al. The effect of high-dose radioiodine treatment on lacrimal gland function in patients with differentiated thyroid carcinoma. Clin Nucl Med. 2007;32:696–9.

    PubMed  Google Scholar 

  34. Solans R, Bosch JA, Galofré P, Porta F, Roselló J, Selva-O’Callagan A, et al. Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. J Nucl Med. 2001;42:738–43.

    CAS  PubMed  Google Scholar 

  35. Bigsby RM, Valluri S, Lopez J, Mendonca MS, Caperell-Grant A, DesRosiers C, et al. Ovarian hormone modulation of radiation-induced cataractogenesis: dose-response studies. Invest Ophthalmol Vis Sci. 2009;50:3304–10.

    PubMed  Google Scholar 

  36. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998;78:547–81.

    CAS  PubMed  Google Scholar 

  37. Sohal RS. Role of oxidative stress and protein oxidation in the aging process. Free Radic Biol Med. 2002;33:37–44.

    CAS  PubMed  Google Scholar 

  38. Shin YJ, Seo JM, Chung TY, Hyon JY, Wee WR. Effect of cysteamine on oxidative stress-induced cell death of human corneal endothelial cells. Curr Eye Res. 2011;36:910–7.

    CAS  PubMed  Google Scholar 

  39. Rosenberg ME, Silkensen J. Clusterin: physiologic and pathophysiologic considerations. Int J Biochem Cell Biol. 1995;27:633–45.

    CAS  PubMed  Google Scholar 

  40. Dumont P, Chainiaux F, Eliaers F, Petropoulou C, Remacle J, Koch-Brandt C, Gonos ES, Toussaint O. Overexpression of apolipoprotein J in human fibroblasts protects against cytotoxicity and premature senescence induced by ethanol and tert-butylhydroperoxide. Cell Stress Chaperones. 2002;7(1):23–35.

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Shin YJ, Kim JH, Seo JM, Lee SM, Hyon JY, Yu YS, Wee WR. Protective effect of clusterin on oxidative stress-induced cell death of human corneal endothelial cells. Mol Vis. 2009;15:2789–95.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Tunon MJ, Sanchez-Campos S, Gutierrez B, Culebras JM, Gonzalez-Gallego J. Effects of FK506 and rapamycin on generation of reactive oxygen species, nitric oxide production and nuclear factor kappa B activation in rat hepatocytes. Biochem Pharmacol. 2003;66:439–45.

    CAS  PubMed  Google Scholar 

  43. Suzuki M, Endo M, Shinohara F, Echigo S, Rikiishi H. Rapamycin suppresses ROS-dependent apoptosis caused by selenomethionine in A549 lung carcinoma cells. Cancer Chemother Pharmacol. 2011;67(5):1129–36.

    CAS  PubMed  Google Scholar 

  44. Huang B, Blanco G, Mercer RW, Fleming T, Pepose JS. Human corneal endothelial cell expression of Na+, K + -adenosine triphosphatase isoforms. Arch Ophthalmol. 2003;121:840–5.

    CAS  PubMed  Google Scholar 

  45. Ng LE, Halliwell B, Wong KP. Nephrotoxic cell death by diclofenac and meloxicam. Biochem Biophys Res Commun. 2008;369:873–7.

    CAS  PubMed  Google Scholar 

  46. Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 2000;267:4904–11.

    CAS  PubMed  Google Scholar 

  47. Thiele K, Bierhaus A, Autschbach F, et al. Cell specific effects of glucocorticoid treatment on the NF-kappaBp65/IkappaBalpha system in patients with Crohn’s disease. Gut. 1999;45:693–704.

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Maher P. The effects of stress and aging on glutathione metabolism. Ageing Res Rev. 2005;4:288–314.

    CAS  PubMed  Google Scholar 

  49. Dickinson DA, Forman HJ. Glutathione in defense and signaling. Ann N Y Acad Sci. 2002;973:488–504.

    CAS  PubMed  Google Scholar 

  50. Hayes JD, McLellan LI. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 1999;31:273–300.

    CAS  PubMed  Google Scholar 

  51. Kofman AE, McGraw MR, Payne CJ. Rapamycin increases oxidative stress response gene expression in adult stem cells. Aging (Albany NY). 2012;4(4):279–89.

    CAS  Google Scholar 

  52. Dutta D, Xu J, Kim JS, Dunn Jr WA, Leeuwenburgh C. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity. Autophagy. 2013;9(3):328–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Pisoni RL, Park GY, Velilla VQ, Thoene JG. Detection and characterization of a transport system mediating cysteamine entry into human fibroblast lysosomes. Specificity for aminoethylthiol and aminoethylsulfide derivatives. J Biol Chem. 1995;270:1179–84.

    CAS  PubMed  Google Scholar 

  54. De Biaggi CP, Barros PS, Silva VV, Brooks DE, Barros SB. Ascorbic acid levels of aqueous humor of dogs after experimental phacoemulsification. Vet Ophthalmol. 2006;9:299–302.

    PubMed  Google Scholar 

  55. Gahl WA, Thoene JG, Schneider JA. Cystinosis: a disorder of lysosomal membrane transport. In: Scriver CR, Beaudet al, Sly WS, et al., editors. The metabolic & molecular bases of inherited disease, vol. 3. 8th ed. New York: McGraw Hill; 2001. p. 5085–108.

    Google Scholar 

  56. Jones NP, Postlethwaite RJ, Noble JL. Clearance of corneal crystals in nephropathic cystinosis by topical cysteamine 0–5%. Br J Ophthalmol. 1991;75:311–2.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Tavares R, Coelho D, Macario MC, Torres A, Quadrado MJ, Murta J. Evaluation of treatment with cysteamine eyedrops for cystinosis with confocal microscopy. Cornea. 2009;28:938–40.

    PubMed  Google Scholar 

  58. Kessler A, Biasibetti M, da Silva Melo DA, Wajner M, Dutra-Filho CS, de Souza Wyse AT, Wannmacher CM. Antioxidant effect of cysteamine in brain cortex of young rats. Neurochem Res. 2008;33:737–44.

    CAS  PubMed  Google Scholar 

  59. Maher P, Lewerenz J, Lozano C, Torres JL. A novel approach to enhancing cellular glutathione levels. J Neurochem. 2008;107:690–700.

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Dominy Jr JE, Simmons CR, Hirschberger LL, Hwang J, Coloso RM, Stipanuk MH. Discovery and characterization of a second mammalian thiol dioxygenase, cysteamine dioxygenase. J Biol Chem. 2007;282:25189–98.

    CAS  PubMed  Google Scholar 

  61. Kamata H, Hirata H. Redox regulation of cellular signalling. Cell Signal. 1999;11:1–14.

    CAS  PubMed  Google Scholar 

  62. Cross AR, Jones OT. Enzymic mechanisms of superoxide production. Biochim Biophys Acta. 1991;1057:281–98.

    CAS  PubMed  Google Scholar 

  63. Panda A, Vanathi M, Kumar A, Dash Y, Priya S. Corneal graft rejection. Surv Ophthalmol. 2007;52:375–96.

    PubMed  Google Scholar 

  64. Des Marchais B, Bazin R, Boisjoly HM, Laughrea PA, Dubé I, Lille S, Roy R. Role of presensitization and donor-recipient crossmatching in corneal graft outcome. Cornea. 1998;17:141–5.

    CAS  PubMed  Google Scholar 

  65. Jonas JB, Rank RM, Budde WM. Immunologic graft reactions after allogenic penetrating keratoplasty. Am J Ophthalmol. 2002;133:437–43.

    PubMed  Google Scholar 

  66. Streilein JW. Anterior chamber associated immune deviation: the privilege of immunity in the eye. Surv Ophthalmol. 1990;35:67–73.

    CAS  PubMed  Google Scholar 

  67. Levenson JE, Brightbill FS. Endothelial rejection in human transplants. Arch Ophthalmol. 1973;89:489–92.

    CAS  PubMed  Google Scholar 

  68. Coster DJ, Williams KA. The impact of corneal allograft rejection on the long-term outcome of corneal transplantation. Am J Ophthalmol. 2005;140:1112–22.

    PubMed  Google Scholar 

  69. Morris RE, Wu J, Shorthouse R. A study of the contrasting effects of cyclosporine, FK 506, and rapamycin on the suppression of allograft rejection. Transplant Proc. 1990;22:1638–41.

    CAS  PubMed  Google Scholar 

  70. McMahon G, Weir MR, Li XC, Mandelbrot DA. The evolving role of mTOR inhibition in transplantation tolerance. J Am Soc Nephrol. 2011;22:408–15.

    CAS  PubMed  Google Scholar 

  71. Chon WJ, Josephson MA. Leflunomide in renal transplantation. Expert Rev Clin Immunol. 2011;7:273–81.

    CAS  PubMed  Google Scholar 

  72. Collier SJ. Immunosuppressive drugs. Curr Opin Immunol. 1989–1990;2:854–8.

    CAS  Google Scholar 

  73. Li YJ, Takizawa H, Kawada T. Role of oxidative stresses induced by diesel exhaust particles in airway inflammation, allergy and asthma: their potential as a target of chemoprevention. Inflamm Allergy Drug Targets. 2010;9:300–5.

    CAS  PubMed  Google Scholar 

  74. Eberlein M, Scheibner KA, Black KE, Collins SL, Chan-Li Y, Powell JD, Horton MR. Anti-oxidant inhibition of hyaluronan fragment-induced inflammatory gene expression. J Inflamm (Lond). 2008;5:20.

    Google Scholar 

  75. Szabo S, Reichlin S. Somatostatin in rat tissues is depleted by cysteamine administration. Endocrinology. 1981;109:2255–7.

    CAS  PubMed  Google Scholar 

  76. Deleuze S, Goudet G. Cysteamine supplementation of in vitro maturation media: a review. Reprod Domest Anim. 2010;45:e476–82.

    CAS  PubMed  Google Scholar 

  77. Anand T, Kumar D, Chauhan MS, Manik RS, Palta P. Cysteamine supplementation of in vitro maturation medium, in vitro culture medium or both media promotes in vitro development of buffalo (Bubalus bubalis) embryos. Reprod Fertil Dev. 2008;20:253–7.

    CAS  PubMed  Google Scholar 

  78. Kessler A, Biasibetti M, Feksa LR, Rech VC, Melo DA, Wajner M, Dutra-Filho CS, Wyse AT, Wannmacher CM. Effects of cysteamine on oxidative status in cerebral cortex of rats. Metab Brain Dis. 2008;23:81–93.

    CAS  PubMed  Google Scholar 

  79. Salam OM. Modulation of inflammatory paw oedema by cysteamine in the rat. Pharmacol Res. 2002;45:275–84.

    PubMed  Google Scholar 

  80. El-Shenawy SM, Abdel-Salam OM, Baiuomy AR, El-Batran S, Arbid MS. Studies on the anti-inflammatory and antinociceptive effects of melatonin in the rat. Pharmacol Res. 2002;46:235–43.

    CAS  PubMed  Google Scholar 

  81. Shin YJ, Hyon JY, Kim S, Koh JW, Kwon SI, Wee WR. Cysteamine suppresses human peripheral blood mononuclear cells–human corneal endothelial cell reaction via reactive oxygen species reduction. Mol Vis. 2011;17:3371–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Williams KA, White MA, Ash JK, Coster DJ. Leukocytes in the graft bed associated with corneal graft failure: analysis by immunohistology and actuarial graft survival. Ophthalmology. 1989;96:38–44.

    CAS  PubMed  Google Scholar 

  83. Smolin G, Biswell R. Corneal graft rejection associated with anterior iris adhesion: case report. Ann Ophthalmol. 1978;10:1603–4.

    CAS  PubMed  Google Scholar 

  84. Khodadoust AA, Silverstein AM. Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol. 1969;8:180–95.

    CAS  PubMed  Google Scholar 

  85. Maenz M, Morcos M, Ritter T. A comprehensive flowcytometric analysis of graft infiltrating lymphocytes, draining lymph nodes and serum during the rejection phase in a fully allogeneic rat cornea transplant model. Mol Vis. 2011;17:420–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Khodr B, Khalil Z. Modulation of inflammation by reactive oxygen species: implications for aging and tissue repair. Free Radic Biol Med. 2001;30:1–8.

    CAS  PubMed  Google Scholar 

  87. George L, Lokhandwala MF, Asghar M. Exercise activates redox-sensitive transcription factors and restores renal D1 receptor function in old rats. Am J Physiol Renal Physiol. 2009;297:F1174–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Vallières L, Rivest S. Interleukin-6 is a needed proinflammatory cytokine in the prolonged neural activity and transcriptional activation of corticotropin-releasing factor during endotoxemia. Endocrinology. 1999;140:3890–903.

    PubMed  Google Scholar 

  89. Tak PP, Firestein GS. NF-κB: a key role in inflammatory diseases. J Clin Invest. 2001;107:7–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Schindler R, Mancilla J, Endres S, Ghorbani R, Clark SC, Dinarello CA. Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990;75:40–7.

    CAS  PubMed  Google Scholar 

  91. Korpinen E, Groop PH, Fagerudd JA, Teppo AM, Akerblom HK, Vaarala O. Increased secretion of TGF-beta1 by peripheral blood mononuclear cells from patients with Type 1 diabetes mellitus with diabetic nephropathy. Diabet Med. 2001;18:121–5.

    CAS  PubMed  Google Scholar 

  92. Libermann TA, Baltimore D. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol. 1990;10:2327–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Bhat-Nakshatri P, Newton TR, Goulet Jr R, Nakshatri HNF. κB activation and interleukin 6 production in fibroblasts by estrogen receptor-negative breast cancer cell-derived interleukin 1α. Proc Natl Acad Sci U S A. 1998;95:6971–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Mou HB, Lin MF, Huang H, Cai Z. Transforming growth factor-β1 modulates lipopolysaccharide-induced cytokine/chemokine production and inhibits nuclear factor-κB, extracellular signal-regulated kinases and p38 activation in dendritic cells in mice. Transplant Proc. 2011;43:2049–52.

    CAS  PubMed  Google Scholar 

  95. Murillo MM, Carmona-Cuenca I, Del Castillo G, Ortiz C, Roncero C, Sánchez A, Fernández M, Fabregat I. Activation of NADPH oxidase by transforming growth factor-beta in hepatocytes mediates up-regulation of epidermal growth factor receptor ligands through a nuclear factor-kappaBdependent mechanism. Biochem J. 2007;405:251–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Flynn TH, Mitchison NA, Ono SJ, Larkin DF. Aqueous humor alloreactive cell phenotypes, cytokines and chemokines in corneal allograft rejection. Am J Transplant. 2008;8:1537–43.

    CAS  PubMed  Google Scholar 

  97. Funding M, Vorum H, Nexo E, Moestrup SK, Ehlers N, Moller HJ. Soluble CD163 and interleukin-6 are increased in aqueous humour from patients with endothelial rejection of corneal grafts. Acta Ophthalmol Scand. 2005;83:234–9.

    CAS  PubMed  Google Scholar 

  98. Sagoo P, Chan G, Larkin DF, George AJ. Inflammatory cytokines induce apoptosis of corneal endothelium through nitric oxide. Invest Ophthalmol Vis Sci. 2004;45:3964–73.

    PubMed  Google Scholar 

  99. Klass BR, Grobbelaar AO, Rolfe KJ. Transforming growth factor β1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgrad Med J. 2009;85:9–14.

    CAS  PubMed  Google Scholar 

  100. Ma FY, Tesch GH, Ozols E, Xie M, Schneider MD, Nikolic-Paterson DJ. TGF-β1-activated kinase-1 regulates inflammation and fibrosis in the obstructed kidney. Am J Physiol Renal Physiol. 2011;300:F1410–21.

    CAS  PubMed  Google Scholar 

  101. Yi K, Chung TY, Hyon JY, Koh JW, Wee WR, Shin YJ. Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells—chemically injured keratocyte reaction. Mol Vis. 2011;17:2665–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Kubota M, Shimmura S, Kubota S, Miyashita H, Kato N, Noda K, Oawa Y, Usui T, Ishida S, Umezawa K, Kurihara T, Tsubota K. Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Invest Ophthalmol Vis Sci. 2011;52:427–33.

    CAS  PubMed  Google Scholar 

  103. Wagoner MD. Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol. 1997;41:275–313.

    CAS  PubMed  Google Scholar 

  104. Nuijts RM. Autologous limbal transplantation in unilateral chemical burns. Doc Ophthalmol. 1999;98:257–66.

    CAS  PubMed  Google Scholar 

  105. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39:44–84.

    CAS  PubMed  Google Scholar 

  106. Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82:47–95.

    PubMed  Google Scholar 

  107. Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med. 2011;208:519–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Zhou Q, Wang Y, Yang L, Wang Y, Chen P, Wang Y, Chen P, Wang Y, Dong X, Xie L. Histone deacetylase inhibitors blocked activation and caused senescence of corneal stromal cells. Mol Vis. 2008;14:2556–65.

    PubMed Central  PubMed  Google Scholar 

  109. Burdon RH, Gill V, Rice-Evans C. Oxidative stress and tumor cell proliferation. Free Radic Res Commun. 1990;11:65–76.

    CAS  PubMed  Google Scholar 

  110. DiBartolomeis SM, Moné JP. Apoptosis: a four-week laboratory investigation for advanced molecular and cellular biology students. Cell Biol Educ. 2003;2:275–95.

    PubMed Central  PubMed  Google Scholar 

  111. Burdon RH, Rice-Evans C. Free radicals and the regulation of mammalian cell proliferation. Free Radic Res Commun. 1989;6:345–58.

    CAS  PubMed  Google Scholar 

  112. Cho YS, Lee J, Lee TH, Lee EY, Lee KU, Park JY, Moon HB. Alpha-lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J Allergy Clin Immunol. 2004;114:429–35.

    CAS  PubMed  Google Scholar 

  113. Zhang WJ, Wei H, Hagen T, Frei B. Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. Proc Natl Acad Sci U S A. 2007;104:4077–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Saja K, Babu MS, Karunagaran D, Sudhakaran PR. Antiinflammatory effect of curcumin involves downregulation of MMP-9 in blood mononuclear cells. Int Immunopharmacol. 2007;7:1659–67.

    CAS  PubMed  Google Scholar 

  115. Coussens LM, Tinkle CL, Hanahan D, Werb Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell. 2000;103:481–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–74.

    CAS  PubMed  Google Scholar 

  117. Matsubara M, Zieske JD, Fini ME. Mechanism of basement membrane dissolution preceding corneal ulceration. Invest Ophthalmol Vis Sci. 1991;32:3221–37.

    CAS  PubMed  Google Scholar 

  118. Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003;3:791–800.

    CAS  PubMed  Google Scholar 

  119. Wahl SM. Transforming growth factor beta (TGF-beta) in inflammation: a cause and a cure. J Clin Immunol. 1992;12:61–74.

    CAS  PubMed  Google Scholar 

  120. Leung JC, Chan LY, Tsang AW, Liu EW, Lam MF, Tang SC, Lai KN. Anti-macrophage migration inhibitory factor reduces transforming growth factor-beta 1 expression in experimental IgA nephropathy. Nephrol Dial Transplant. 2004;19:1976–85.

    CAS  PubMed  Google Scholar 

  121. Chaiyaroj SC, Rutta AS, Muenthaisong K, Watkins P, Na Ubol M, Looareesuwan S. Reduced levels of transforming growth factor-β1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria. Acta Trop. 2004;89:319–27.

    CAS  PubMed  Google Scholar 

  122. Andresen JL, Ehlers N. Chemotaxis of human keratocytes is increased by platelet-derived growth factor-BB, epidermal growth factor, transforming growth factor-alpha, acidic fibroblast growth factor, insulin-like growth factor-I, and transforming growth factor-beta. Curr Eye Res. 1998;17:79–87.

    CAS  PubMed  Google Scholar 

  123. Shin YJ, Hyon JY, Choi WS, Yi K, Chung ES, Chung TY, Wee WR. Chemical injury-induced corneal opacity and neovascularization reduced by rapamycin via TGF-β1/ERK pathways regulation. Invest Ophthalmol Vis Sci. 2013;54:4452–8.

    CAS  PubMed  Google Scholar 

  124. Gadjeva M, Nagashima J, Zaidi T, Mitchell RA, Pier GB. Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis. PLoS Pathog. 2010;6:e1000826.

    PubMed Central  PubMed  Google Scholar 

  125. Flaster H, Bernhagen J, Calandra T, Bucala R. The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity. Mol Endocrinol. 2007;21:1267–80.

    CAS  PubMed  Google Scholar 

  126. Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, Cerami A, Bucala R. MIF as a glucocorticoid-induced modulator of cytokine production. Nature. 1995;377:68–71.

    CAS  PubMed  Google Scholar 

  127. Yu X, Lin SG, Huang XR, Bacher M, Leng L, Bucala R, Lan HY. Macrophage migration inhibitory factor induces MMP-9 expression in macrophages via the MEK-ERK MAP kinase pathway. J Interferon Cytokine Res. 2007;27:103–9.

    CAS  PubMed  Google Scholar 

  128. Panda A, Jain M, Vanathi M, et al. Topical autologous platelet-rich plasma eyedrops for acute corneal chemical injury. Cornea. 2012;31:989–93.

    PubMed  Google Scholar 

  129. Dohlman CH, Cade F, Pfister R. Chemical burns to the eye: paradigm shifts in treatment. Cornea. 2011;30:613–4.

    PubMed  Google Scholar 

  130. Kwon YS, Kim JC. Inhibition of corneal neovascularization by rapamycin. Exp Mol Med. 2006;38:173–9.

    CAS  PubMed  Google Scholar 

  131. Kwon YS, Hong HS, Kim JC, Shin JS, Son Y. Inhibitory effect of rapamycin on corneal neovascularization in vitro and in vivo. Invest Ophthalmol Vis Sci. 2005;46:454–60.

    PubMed  Google Scholar 

  132. Sakimoto T, Sugaya S, Ishimori A, Sawa M. Anti-inflammatory effect of IL-6 receptor blockade in corneal alkali burn. Exp Eye Res. 2012;97:98–104.

    CAS  PubMed  Google Scholar 

  133. Tzeng HE, Tsai CH, Chang ZL, et al. Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. Biochem Pharmacol. 2013;85(4):531–40.

    CAS  PubMed  Google Scholar 

  134. Ito TK, Ishii G, Chiba H, Ochiai A. The VEGF angiogenic switch of fibroblasts is regulated by MMP-7 from cancer cells. Oncogene. 2007;26:7194–203.

    CAS  PubMed  Google Scholar 

  135. Wilson SE. Corneal myofibroblast biology and pathobiology: generation, persistence, and transparency. Exp Eye Res. 2012;99:78–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  136. Luckett-Chastain LR, Gallucci RM. Interleukin (IL)-6 modulates transforming growth factor-betaexpression in skin and dermal fibroblasts from IL-6-deficientmice. Br J Dermatol. 2009;161:237–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Tandon A, Tovey JC, Sharma A, Gupta R, Mohan RR. Role of transforming growth factor Beta in corneal function, biology and pathology. Curr Mol Med. 2010;10:5655–78.

    Google Scholar 

  138. Sonpavde G, Choueiri TK. Biomarkers: the next therapeutic hurdle in metastatic renal cell carcinoma. Br J Cancer. 2012;107:1009–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Gurk-Turner C, Manitpisitkul W, Cooper M. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor. Transplantation. 2012;94:659–68.

    CAS  PubMed  Google Scholar 

  140. Kahan BD. Sirolimus: a comprehensive review. Expert Opin Pharmacother. 2001;2:1903–17.

    CAS  PubMed  Google Scholar 

  141. Nair S, Ren J. Autophagy and cardiovascular aging: lesson learned from rapamycin. Cell Cycle. 2012;11:2092–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  142. Tulek B, Kiyan E, Toy H, et al. Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats. Clin Invest Med. 2011;34:E341.

    CAS  PubMed  Google Scholar 

  143. Xu T, Xie JY, Wang WM, Ren H, Chen N. Impact of rapamycin on peritoneal fibrosis and transport function. Blood Purif. 2012;34:48–57.

    PubMed  Google Scholar 

  144. Kure T, Chang JH, Kato T, et al. Corneal neovascularization after excimer keratectomy wounds in matrilysin-deficient mice. Invest Ophthalmol Vis Sci. 2003;44:137–44.

    PubMed  Google Scholar 

  145. Xing D, Sun X, Li J, Cui M, Tan-Allen K, Bonanno JA. Hypoxia preconditioning protects corneal stromal cells against induced apoptosis. Exp Eye Res. 2006;82:780–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Shaul YD, Seger R. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta. 2007;1773:1213–26.

    CAS  PubMed  Google Scholar 

  147. Kretzschmar M, Doody J, Timokhina I, Massague J. A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev. 1999;13:804–16.

    CAS  PubMed Central  PubMed  Google Scholar 

  148. Alarcon C, Zaromytidou A-I, Xi Q, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-b pathways. Cell. 2009;139:757–69.

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Hayashida T, Decaestecker M, Schnaper HW. Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells. FASEB J. 2003;17:1576–8.

    CAS  PubMed  Google Scholar 

  150. Massagué J, Seoane J, Wotton D. Smad transcription factors. Genes Dev. 2005;19:2783–810.

    PubMed  Google Scholar 

  151. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18:1926–45.

    CAS  PubMed  Google Scholar 

  152. Corradetti MN, Guan KL. Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene. 2006;25:6347–60.

    CAS  PubMed  Google Scholar 

  153. Tsokas P, Ma T, Iyengar R, Landau EM, Blitzer RD. Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway. J Neurosci. 2007;27:5885–94.

    CAS  PubMed  Google Scholar 

  154. Winter JN, Jefferson LS, Kimball SR. ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling. Am J Physiol Cell Physiol. 2011;300:C1172–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Kishimoto T, Akira S, Narazaki M, Taga T. Interleukin-6 family of cytokines and gp130. Blood. 1995;86:1243–54.

    CAS  PubMed  Google Scholar 

  156. Kennedy M, Kim KH, Harten B, et al. Ultraviolet irradiation induces the production of multiple cytokines by human corneal cells. Invest Ophthalmol Vis Sci. 1997;38:2483–91.

    CAS  PubMed  Google Scholar 

  157. Cole N, Bao S, Willcox M, Husband AJ. Expression of interleukin-6 in the cornea in response to infection with different strains of Pseudomonas aeruginosa. Infect Immun. 1999;67:2497–502.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Cubitt CL, Lausch RN, Oakes JE. Differences in interleukin-6 gene expression between cultured human corneal epithelial cells and keratocytes. Invest Ophthalmol Vis Sci. 1995;36:330–6.

    CAS  PubMed  Google Scholar 

  159. Park CY, Zhu Z, Zhang C, Moon CS, Chuck RS. Cellular redox state predicts in vitro corneal endothelial cell proliferation capacity. Exp Eye Res. 2006;83:903–10.

    CAS  PubMed  Google Scholar 

  160. Kakkar P, Singh BK. Mitochondria: a hub of redox activities and cellular distress control. Mol Cell Biochem. 2007;305:235–53.

    CAS  PubMed  Google Scholar 

  161. Armstrong JS. Mitochondria: a target for cancer therapy. Br J Pharmacol. 2006;147:239–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 2008;266:37–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  163. Chance B, Schoener B, Oshino R, Itshak F, Nakase Y. Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples: NADH and flavoprotein fluorescence signals. J Biol Chem. 1979;254:4764–71.

    CAS  PubMed  Google Scholar 

  164. Ramey NA, Park CY, Gehlbach PL, Chuck RS. Imaging mitochondria in living corneal endothelial cells using autofluorescence microscopy. Photochem Photobiol. 2007;83:1325–9.

    CAS  PubMed  Google Scholar 

  165. Reyes JM, Fermanian S, Yang F, et al. Metabolic changes in mesenchymal stem cells in osteogenic medium measured by autofluorescence spectroscopy. Stem Cells. 2006;24:1213–7.

    CAS  PubMed  Google Scholar 

  166. Richter C, Gogvadze V, Laffranchi R, et al. Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta. 1995;1271:67–74.

    PubMed  Google Scholar 

  167. Gutteridge JM, Halliwell B. Free radicals and antioxidants in the year 2000: a historical look to the future. Ann N Y Acad Sci. 2000;899:136–47.

    CAS  PubMed  Google Scholar 

  168. Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991;51:794–8.

    CAS  PubMed  Google Scholar 

  169. Zamzami N, Larochette N, Kroemer G. Mitochondrial permeability transition in apoptosis and necrosis. Cell Death Differ. 2005;12:1478–80.

    CAS  PubMed  Google Scholar 

  170. Murrell GA, Francis MJ, Bromley L. Modulation of fibroblast proliferation by oxygen free radicals. Biochem J. 1990;265:659–65.

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Nicotera TM, Privalle C, Wang TC, Oshimura M, Barrett JC. Differential proliferative responses of Syrian hamster embryo fibroblasts to paraquat-generated superoxide radicals depending on tumor suppressor gene function. Cancer Res. 1994;54:3884–8.

    CAS  PubMed  Google Scholar 

  172. Preeta R, Nair RR. Stimulation of cardiac fibroblast proliferation by cerium: a superoxide anion-mediated response. J Mol Cell Cardiol. 1999;31:1573–80.

    CAS  PubMed  Google Scholar 

  173. Attene-Ramos MS, Kitiphongspattana K, Ishii-Schrade K, Gaskins HR. Temporal changes of multiple redox couples from proliferation to growth arrest in IEC-6 intestinal epithelial cells. Am J Physiol Cell Physiol. 2005;289:C1220–8.

    CAS  PubMed  Google Scholar 

  174. Pani G, Colavitti R, Bedogni B, Anzevino R, Borrello S, Galeotti T. A redox signaling mechanism for density-dependent inhibition of cell growth. J Biol Chem. 2000;275:38891–9.

    CAS  PubMed  Google Scholar 

  175. Patterson GH, Knobel SM, Arkhammar P, Thastrup O, Piston DW. Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet beta cells. Proc Natl Acad Sci U S A. 2000;97:5203–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  176. Hassinen I, Chance B. Oxidation-reduction properties of the mitochondrial flavoprotein chain. Biochem Biophys Res Commun. 1968;28:895–900.

    Google Scholar 

  177. Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA. Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med. 2012;52(4):735–46.

    CAS  PubMed  Google Scholar 

  178. Tsai YY, Cheng YW, Lee H, Tsai FJ, Tseng SH, Lin CL, Chang KC. Oxidative DNA damage in pterygium. Mol Vis. 2005;25(11):71–5.

    Google Scholar 

  179. Maxia C, Perra MT, Demurtas P, Minerba L, Murtas D, Piras F, Corbu A, Gotuzzo DC, Cabrera RG, Ribatti D, Sirigu P. Expression of survivin protein in pterygium and relationship with oxidative DNA damage. J Cell Mol Med. 2008;12(6A):2372–80.

    CAS  PubMed  Google Scholar 

  180. Nakamura S, Shibuya M, Nakashima H, Hisamura R, Masuda N, Imagawa T, Uehara M, Tsubota K. Involvement of oxidative stress on corneal epithelial alterations in a blink-suppressed dry eye. Invest Ophthalmol Vis Sci. 2007;48(4):1552–8.

    PubMed  Google Scholar 

  181. Kojima T, Wakamatsu TH, Dogru M, Ogawa Y, Igarashi A, Ibrahim OM, Inaba T, Shimizu T, Noda S, Obata H, Nakamura S, Wakamatsu A, Shirasawa T, Shimazaki J, Negishi K, Tsubota K. Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. Am J Pathol. 2012;180:1879–96.

    CAS  PubMed  Google Scholar 

  182. Pagano G, Castello G, Pallardó FV. Sjøgren’s syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials. Free Radic Res. 2013;47:71–3.

    PubMed  Google Scholar 

  183. Lal MA, Brismar H, Eklöf AC, Aperia A. Role of oxidative stress in advanced glycation end product-induced mesangial cell activation. Kidney Int. 2002;61:2006–14.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Hallym University College of Medicine, 948-1 Daerim1-dong, Youngdeungpo-gu, Seoul, 150-950, South Korea

    Eunbi Kim, Sam Young Yoon & Young Joo Shin M.D.

Authors
  1. Eunbi Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sam Young Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Young Joo Shin M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Joo Shin M.D. .

Editor information

Editors and Affiliations

  1. Innovative Vision Products Inc., Moscow, Russia, Innovative Vision Products, Inc.,, County of New Castle, Delaware, USA

    Mark A. Babizhayev

  2. Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center; Key Laboratory of Protein Chemistry and Developmental Biology of Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China, Omaha, Nebraska, USA

    David Wan-Cheng Li

  3. Department of Pharmaceutical Sciences and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

    Anne Kasus-Jacobi

  4. Department of Ophthalmology, University of Pristina, Faculty of Medicine, Kosovska Mitrovica, Serbia

    Lepša Žorić

  5. Ophthalmology, Miguel Hernandez University, Alicante, Spain

    Jorge L. Alió

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kim, E., Yoon, S.Y., Shin, Y.J. (2015). Oxidative Stress in Cornea. In: Babizhayev, M., Li, DC., Kasus-Jacobi, A., Žorić, L., Alió, J. (eds) Studies on the Cornea and Lens. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1935-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation