Abstract
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 language | English |
|---|---|
| Pages (from-to) | 5780-5787 |
| Number of pages | 8 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 53 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2012 Aug |
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ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
- Medicine(all)
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Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions. / Onouchi, Hiromi; Ishii, Takamasa; Miyazawa, Masaki; Uchino, Yuichi; Yasuda, Kayo; Hartman, Phil S.; Kawai, Kenji; Tsubota, Kazuo; Ishii, Naoaki.
In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 9, 08.2012, p. 5780-5787.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial superoxide anion overproduction in Tet-mev-1 transgenic mice accelerates age-dependent corneal cell dysfunctions
AU - Onouchi, Hiromi
AU - Ishii, Takamasa
AU - Miyazawa, Masaki
AU - Uchino, Yuichi
AU - Yasuda, Kayo
AU - Hartman, Phil S.
AU - Kawai, Kenji
AU - Tsubota, Kazuo
AU - Ishii, Naoaki
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84871695366&partnerID=8YFLogxK
U2 - 10.1167/iovs.12-9573
DO - 10.1167/iovs.12-9573
M3 - Article
C2 - 22786907
AN - SCOPUS:84871695366
VL - 53
SP - 5780
EP - 5787
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 9
ER -