Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions

Hiromi Onouchi, Takamasa Ishii, Masaki Miyazawa, Yuichi Uchino, Kayo Yasuda, Phil S. Hartman, Kenji Kawai, Kazuo Tsubota, Naoaki Ishii

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Purpose. The Tet-mev-1 mouse expressing a mitochondrial complex-II mutated SDHCV69E gene controlled by a tetracycline (Tet)-On/Off system can overproduce O2·- and is a versatile whole-animal model for studying mitochondrial oxidative stress. Here we report a series of age-dependent variations in corneal epithelium, endothelium, and parenchymal cells of the Tet-mev-1 mice relative to wild-type C57BL/6j mice. Methods. Measurements of (1) mitochondrial electron transport enzyme activities; (2) O2·- production; (3) carbonylated protein, and 8-hydroxydeoxyguanosine (8-OHdG) levels as markers of oxidative stress; (4) pathologic analyses under optical and electron microscopy; (5) hematoxylin-eosin or toluidine-blue staining; and (6) immunohistochemistry with an anti-β-catenin antibody were performed in the eye, especially the cornea. Results. Complex II-III activity was decreased by electron leakage between complex II and CoQ. This resulted in increased age-dependent intracellular oxidative stress in the eye of Tet-mev-1 mice. Corneal epithelialization was delayed in Tet-mev-1 mice after 20% ethanol treatment, as the number of cells and mitotic cells decreased in the corneal epithelium of Tet-mev-1 mice compared with that of wild type. The age-dependent decrease in cell number accelerated in the corneal endothelium cells. Moreover, it was suggested that the corneal thickness was decreased by thinning of parenchymal cells with age in Tet-mev-1 mice. Conclusions. These results suggest that mitochondrial oxidative stress with electron transport chain dysfunction can influence pathogenesis and progression of age-related corneal diseases, as well as generalized corneal aging acceleration.

Original languageEnglish
Pages (from-to)5780-5787
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number9
Publication statusPublished - 2012 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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