Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy
The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mou...
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MDPI AG
2024-02-01
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| author | Chun-Yen Wu Da-Fong Song Zhi-Jia Chen Chao-Sheng Hu David Pei-Cheng Lin Han-Hsin Chang |
| author_facet | Chun-Yen Wu Da-Fong Song Zhi-Jia Chen Chao-Sheng Hu David Pei-Cheng Lin Han-Hsin Chang |
| author_sort | Chun-Yen Wu |
| collection | DOAJ |
| description | The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial–mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases. |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-04-24T18:32:54Z |
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| spelling | doaj.art-fcdfcc3729b74ff78818b999d0558f162024-03-27T13:22:02ZengMDPI AGBiology2079-77372024-02-0113313310.3390/biology13030133Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous KeratopathyChun-Yen Wu0Da-Fong Song1Zhi-Jia Chen2Chao-Sheng Hu3David Pei-Cheng Lin4Han-Hsin Chang5Department of Nutrition, Chung Shan Medical University, Taichung City 402, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung City 402, TaiwanDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 402, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung City 402, TaiwanDepartment of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung City 402, TaiwanDepartment of Nutrition, Chung Shan Medical University, Taichung City 402, TaiwanThe Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial–mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.https://www.mdpi.com/2079-7737/13/3/133Klotho null mutationage-related cornea degenerationFuchs endothelial corneal dystrophybullous keratopathydry eye diseasemurine model |
| spellingShingle | Chun-Yen Wu Da-Fong Song Zhi-Jia Chen Chao-Sheng Hu David Pei-Cheng Lin Han-Hsin Chang Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy Biology Klotho null mutation age-related cornea degeneration Fuchs endothelial corneal dystrophy bullous keratopathy dry eye disease murine model |
| title | Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy |
| title_full | Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy |
| title_fullStr | Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy |
| title_full_unstemmed | Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy |
| title_short | Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy |
| title_sort | absence of the klotho function causes cornea degeneration with specific features resembling fuchs endothelial corneal dystrophy and bullous keratopathy |
| topic | Klotho null mutation age-related cornea degeneration Fuchs endothelial corneal dystrophy bullous keratopathy dry eye disease murine model |
| url | https://www.mdpi.com/2079-7737/13/3/133 |
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