Corneal oxidative damage in keratoconus cells due to decreased oxidant elimination from modified expression levels of SOD enzymes, PRDX6, SCARA3, CPSF3, and FOXM1.

Purpose: To compare the levels of gene expression for enzymes involved in production and elimination of reactive oxygen/nitrogen species (ROS/RNS) in normal human corneal cells (NL cells) with those in human corneal cells with keratoconus (KC cells) in vitro. Methods: Primary NL and KC stromal fibro...

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Publicado en:Journal of Ophthalmic & Vision Research Vol. 14; no. 1; pp. 62 - 71
Autores principales: Atilano, Shari, Lee, Daniel, Fukuhara, Paula, Chwa, Marilyn, Nesburn, Anthony, Udar, Nitin, Kenney, Cristina
Formato: pictorial research tables/charts Journal Article
Publicado: Knowledge E DMCC Jan-Mar2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jan-Mar2019
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      pub: Knowledge E DMCC
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        atl: Corneal oxidative damage in keratoconus cells due to decreased oxidant elimination from modified expression levels of SOD enzymes, PRDX6, SCARA3, CPSF3, and FOXM1.
      aug:
        au:
          Atilano, Shari
          Lee, Daniel
          Fukuhara, Paula
          Chwa, Marilyn
          Nesburn, Anthony
          Udar, Nitin
          Kenney, Cristina
        affil: Department of Ophthalmology, Gavin Herbert Eye Institute, University of California Irvine, Irvine, CA
      sug:
        subj:
          Corneal Injuries Pathology
          Keratoconus Pathology
          Oxidative Stress
          Oxidants Adverse Effects
          Gene Expression
          Superoxide Dismutase Metabolism
          Human
          Comparative Studies
          In Vitro Studies
          Reactive Oxygen Species
          Reactive Nitrogen Species
          Polymerase Chain Reaction Methods
          Biological Assay Methods
          Immunohistochemistry
          Descriptive Statistics
      ab: Purpose: To compare the levels of gene expression for enzymes involved in production and elimination of reactive oxygen/nitrogen species (ROS/RNS) in normal human corneal cells (NL cells) with those in human corneal cells with keratoconus (KC cells) in vitro. Methods: Primary NL and KC stromal fibroblast cultures were incubated with apocynin (an inhibitor of NADPH oxidase) or N-nitro-L-arginine (N-LLA; an inhibitor of nitric oxide synthase). ROS/RNS levels were measured using an H2DCFDA fluorescent assay. The RT2 Profiler™ PCR Array for Oxidative Stress and Antioxidant Defense was used for initial screening of the NL and KC cultures. Transcription levels for genes related to production or elimination of ROS/RNS were analyzed using quantitative PCR. Immunohistochemistry was performed on 10 intact human corneas using antibodies against SCARA3 and CPSF3. Results: Array screening of 84 antioxidant-related genes identified 12 genes that were differentially expressed between NL and KC cultures. Compared with NL cells, quantitative PCR showed that KC cells had decreased expression of antioxidant genes SCARA3 isoform 2 (0.59-fold, P = 0.02) and FOXM1 isoform 1 (0.61-fold, P = 0.03). KC cells also had downregulation of the antioxidant genes SOD1 (0.4-fold, P = 0.0001) and SOD3 (0.37-fold, P = 0.02) but increased expression of SOD2 (3.3-fold, P < 0.0001), PRDX6 (1.47-fold, P = 0.01), and CPSF3 (1.44-fold, P = 0.02). Conclusion: The difference in expression of antioxidant enzymes between KC and NL suggests that the oxidative stress imbalances found in KC are caused by defects in ROS/RNS removal rather than increased ROS/RNS production.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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