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Involvement of NADPH oxidases in alkali burn-induced corneal injury

  • Authors:
    • Xue-Jun Gu
    • Xian Liu
    • Ying-Ying Chen
    • Yao Zhao
    • Man Xu
    • Xiao-Jian Han
    • Qiu-Ping Liu
    • Jing-Lin Yi
    • Jing-Ming Li
  • View Affiliations / Copyright

    Affiliations: Affiliated Eye Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 75-82
    |
    Published online on: May 17, 2016
       https://doi.org/10.3892/ijmm.2016.2594
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Abstract

Chemical burns are a major cause of corneal injury. Oxidative stress, inflammatory responses and neovascularization after the chemical burn aggravate corneal damage, and lead to loss of vision. Although NADPH oxidases (Noxs) play a crucial role in the production of reactive oxygen species (ROS), the role of Noxs in chemical burn-induced corneal injury remains to be elucidated. In the present study, the transcription and expression of Noxs in corneas were examined by RT-qPCR, western blot analysis and immunofluorescence staining. It was found that alkali burns markedly upregulated the transcription and expression of Nox2 and Nox4 in human or mouse corneas. The inhibition of Noxs by diphenyleneiodonium (DPI) or apocynin (Apo) effectively attenuated alkali burn-induced ROS production and decreased 3-nitrotyrosine (3-NT) protein levels in the corneas. In addition, Noxs/CD11b double‑immunofluorescence staining indicated that Nox2 and Nox4 were partially co-localized with CD11b. DPI or Apo prevented the infiltration of CD11b-positive inflammatory cells, and inhibited the transcription of inflammatory cytokines following alkali burn-induced corneal injury. In our mouse model of alkali burn-induced corneal injury, corneal neovascularization (CNV) occurred on day 3, and it affected 50% of the whole area of the cornea on day 7, and on day 14, CNV coverage of the cornea reached maximum levels. DPI or Apo effectively attenuated alkali burn‑induced CNV and decreased the mRNA levels of angiogenic factors, including vascular endothelial growth factor (VEGF), VEGF receptors and matrix metalloproteinases (MMPs). Taken together, our data indicate that Noxs play a role in alkali burn-induced corneal injury by regulating oxidative stress, inflammatory responses and CNV, and we thus suggest that Noxs are a potential therapeutic target in the future treatment of chemical-induced corneal injury.
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1 

Wagoner MD: Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol. 41:275–313. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Kubota M, Shimmura S, Kubota S, Miyashita H, Kato N, Noda K, Ozawa Y, Usui T, Ishida S, Umezawa K, et al: Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model. Invest Ophthalmol Vis Sci. 52:427–433. 2011. View Article : Google Scholar

3 

Conners MS, Urbano F, Vafeas C, Stoltz RA, Dunn MW and Schwartzman ML: Alkali burn-induced synthesis of inflammatory eicosanoids in rabbit corneal epithelium. Invest Ophthalmol Vis Sci. 38:1963–1971. 1997.PubMed/NCBI

4 

Finkel T: Oxidant signals and oxidative stress. Curr Opin Cell Biol. 15:247–254. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Mokini Z, Marcovecchio ML and Chiarelli F: Molecular pathology of oxidative stress in diabetic angiopathy: role of mitochondrial and cellular pathways. Diabetes Res Clin Pract. 87:313–321. 2010. View Article : Google Scholar

6 

Hakim FA and Pflueger A: Role of oxidative stress in diabetic kidney disease. Med Sci Monit. 16:RA37–RA48. 2010.PubMed/NCBI

7 

Blasiak J, Petrovski G, Veréb Z, Facskó A and Kaarniranta K: Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration. BioMed Res Int. 2014:7680262014. View Article : Google Scholar : PubMed/NCBI

8 

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

9 

Saika S, Miyamoto T, Yamanaka O, Kato T, Ohnishi Y, Flanders KC, Ikeda K, Nakajima Y, Kao WW, Sato M, et al: Therapeutic effect of topical administration of SN50, an inhibitor of nuclear factor-kappaB, in treatment of corneal alkali burns in mice. Am J Pathol. 166:1393–1403. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Zhou AY, Bai YJ, Zhao M, Yu WZ and Li XX: KH902, a recombinant human VEGF receptor fusion protein, reduced the level of placental growth factor in alkali burn induced-corneal neovascularization. Ophthalmic Res. 50:180–186. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Carter RT, Kambampati R, Murphy CJ and Bentley E: Expression of matrix metalloproteinase 2 and 9 in experimentally wounded canine corneas and spontaneous chronic corneal epithelial defects. Cornea. 26:1213–1219. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Sumimoto H, Miyano K and Takeya R: Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun. 338:677–686. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Bedard K and Krause KH: The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 87:245–313. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Sareila O, Kelkka T, Pizzolla A, Hultqvist M and Holmdahl R: NOX2 complex-derived ROS as immune regulators. Antioxid Redox Signal. 15:2197–2208. 2011. View Article : Google Scholar

15 

Nisimoto Y, Diebold BA, Cosentino-Gomes D and Lambeth JD: Nox4: a hydrogen peroxide-generating oxygen sensor. Biochemistry. 53:5111–5120. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Geiszt M, Kopp JB, Várnai P and Leto TL: Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci USA. 97:8010–8014. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Hilenski LL, Clempus RE, Quinn MT, Lambeth JD and Griendling KK: Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 24:677–683. 2004. View Article : Google Scholar

18 

Kuroda J, Nakagawa K, Yamasaki T, Nakamura K, Takeya R, Kuribayashi F, Imajoh-Ohmi S, Igarashi K, Shibata Y, Sueishi K and Sumimoto H: The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells. Genes Cells. 10:1139–1151. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Ellis EA, Grant MB, Murray FT, Wachowski MB, Guberski DL, Kubilis PS and Lutty GA: Increased NADH oxidase activity in the retina of the BBZ/Wor diabetic rat. Free Radic Biol Med. 24:111–120. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Petry A, Djordjevic T, Weitnauer M, Kietzmann T, Hess J and Görlach A: NOX2 and NOX4 mediate proliferative response in endothelial cells. Antioxid Redox Signal. 8:1473–1484. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Manea A, Tanase LI, Raicu M and Simionescu M: Transcriptional regulation of NADPH oxidase isoforms, Nox1 and Nox4, by nuclear factor-kappaB in human aortic smooth muscle cells. Biochem Biophys Res Commun. 396:901–907. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Deem TL and Cook-Mills JM: Vascular cell adhesion molecule 1 (VCAM-1) activation of endothelial cell matrix metalloproteinases: role of reactive oxygen species. Blood. 104:2385–2393. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Li J, Wang JJ, Yu Q, Chen K, Mahadev K and Zhang SX: Inhibition of reactive oxygen species by Lovastatin down-regulates vascular endothelial growth factor expression and ameliorates blood-retinal barrier breakdown in db/db mice: role of NADPH oxidase 4. Diabetes. 59:1528–1538. 2010. View Article : Google Scholar : PubMed/NCBI

24 

O'Brien WJ, Krema C, Heimann T and Zhao H: Expression of NADPH oxidase in rabbit corneal epithelial and stromal cells in culture. Invest Ophthalmol Vis Sci. 47:853–863. 2006. View Article : Google Scholar : PubMed/NCBI

25 

O'Brien WJ, Heimann T and Rizvi F: NADPH oxidase expression and production of superoxide by human corneal stromal cells. Mol Vis. 15:2535–2543. 2009.PubMed/NCBI

26 

Ren S, Zhang F, Li C, Jia C, Li S, Xi H, Zhang H, Yang L and Wang Y: Selection of housekeeping genes for use in quantitative reverse transcription PCR assays on the murine cornea. Mol Vis. 16:1076–1086. 2010.PubMed/NCBI

27 

Matthiesen S, Lindemann D, Warnken M, Juergens UR and Racké K: Inhibition of NADPH oxidase by apocynin inhibits lipopolysaccharide (LPS) induced up-regulation of arginase in rat alveolar macrophages. Eur J Pharmacol. 579:403–410. 2008. View Article : Google Scholar

28 

Ahsan H: 3-Nitrotyrosine: A biomarker of nitrogen free radical species modified proteins in systemic autoimmunogenic conditions. Hum Immunol. 74:1392–1399. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Benayoun Y, Casse G, Forte R, Dallaudière B, Adenis JP and Robert PY: Corneal neovascularization: epidemiological, physiopathological, and clinical features. J Fr Ophtalmol. 36:627–639. 2013.In French. View Article : Google Scholar : PubMed/NCBI

30 

Hamill CE, Bozorg S, Peggy Chang HY, Lee H, Sayegh RR, Shukla AN and Chodosh J: Corneal alkali burns: a review of the literature and proposed protocol for evaluation and treatment. Int Ophthalmol Clin. 53:185–194. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Cejkova J, Trosan P, Cejka C, Lencova A, Zajicova A, Javorkova E, Kubinova S, Sykova E and Holan V: Suppression of alkali-induced oxidative injury in the cornea by mesenchymal stem cells growing on nanofiber scaffolds and transferred onto the damaged corneal surface. Exp Eye Res. 116:312–323. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Jiang F, Zhang Y and Dusting GJ: NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev. 63:218–242. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Sotozono C, He J, Matsumoto Y, Kita M, Imanishi J and Kinoshita S: Cytokine expression in the alkali-burned cornea. Curr Eye Res. 16:670–676. 1997. View Article : Google Scholar : PubMed/NCBI

34 

Ushio-Fukai M: Redox signaling in angiogenesis: role of NADPH oxidase. Cardiovasc Res. 71:226–235. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Shakiba Y, Mansouri K, Arshadi D and Rezaei N: Corneal neovascularization: molecular events and therapeutic options. Recent Pat Inflamm Allergy Drug Discov. 3:221–231. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Lassègue B and Griendling KK: NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol. 30:653–661. 2010. View Article : Google Scholar :

37 

Nayernia Z, Jaquet V and Krause KH: New insights on NOX enzymes in the central nervous system. Antioxid Redox Signal. 20:2815–2837. 2014. View Article : Google Scholar :

38 

Kimura M, Rabbani ZN, Zodda AR, Yan H, Jackson IL, Polascik TJ, Donatucci CF, Moul JW, Vujaskovic Z and Koontz BF: Role of oxidative stress in a rat model of radiation-induced erectile dysfunction. J Sex Med. 9:1535–1549. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Spencer NY and Engelhardt JF: The basic biology of redoxosomes in cytokine-mediated signal transduction and implications for disease-specific therapies. Biochemistry. 53:1551–1564. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Gu X, Liu X, Chen Y, Zhao Y, Xu M, Han X, Liu Q, Yi J and Li J: Involvement of NADPH oxidases in alkali burn-induced corneal injury. Int J Mol Med 38: 75-82, 2016.
APA
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X. ... Li, J. (2016). Involvement of NADPH oxidases in alkali burn-induced corneal injury. International Journal of Molecular Medicine, 38, 75-82. https://doi.org/10.3892/ijmm.2016.2594
MLA
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X., Liu, Q., Yi, J., Li, J."Involvement of NADPH oxidases in alkali burn-induced corneal injury". International Journal of Molecular Medicine 38.1 (2016): 75-82.
Chicago
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X., Liu, Q., Yi, J., Li, J."Involvement of NADPH oxidases in alkali burn-induced corneal injury". International Journal of Molecular Medicine 38, no. 1 (2016): 75-82. https://doi.org/10.3892/ijmm.2016.2594
Copy and paste a formatted citation
x
Spandidos Publications style
Gu X, Liu X, Chen Y, Zhao Y, Xu M, Han X, Liu Q, Yi J and Li J: Involvement of NADPH oxidases in alkali burn-induced corneal injury. Int J Mol Med 38: 75-82, 2016.
APA
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X. ... Li, J. (2016). Involvement of NADPH oxidases in alkali burn-induced corneal injury. International Journal of Molecular Medicine, 38, 75-82. https://doi.org/10.3892/ijmm.2016.2594
MLA
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X., Liu, Q., Yi, J., Li, J."Involvement of NADPH oxidases in alkali burn-induced corneal injury". International Journal of Molecular Medicine 38.1 (2016): 75-82.
Chicago
Gu, X., Liu, X., Chen, Y., Zhao, Y., Xu, M., Han, X., Liu, Q., Yi, J., Li, J."Involvement of NADPH oxidases in alkali burn-induced corneal injury". International Journal of Molecular Medicine 38, no. 1 (2016): 75-82. https://doi.org/10.3892/ijmm.2016.2594
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