| Abstrakt: |
Simple Summary: The Klotho null mutation leads to accelerated senescence in many organs. The effects of an absence of the Klotho function on the cornea remain largely unknown. This study elucidates the impact of the Klotho loss-of-function on corneas. The results show endothelial cell-shedding, reduced corneal epithelial cell density, and decreased cornea stromal layer thickness in Klotho mutant mice. Furthermore, guttae formation and the desquamation of wing cells were significantly increased with the Klotho loss of function, comparable to the conditions of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed oxidative stress-induced apoptosis, inflammation, and extracellular matrix remodeling, resulting in the disruption of epithelial repair and maintenance. Thus, the Klotho null mutation model can be useful for studying cornea degeneration, encompassing senescent corneal diseases, such as dry eye, 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. 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. [ABSTRACT FROM AUTHOR] |
