| First Author | Zhang L | Year | 2020 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 61 |
| Issue | 8 | Pages | 20 |
| PubMed ID | 32668000 | Mgi Jnum | J:292479 |
| Mgi Id | MGI:6448921 | Doi | 10.1167/iovs.61.8.20 |
| Citation | Zhang L, et al. (2020) Excess Transforming Growth Factor-alpha Changed the Cell Properties of Corneal Epithelium and Stroma. Invest Ophthalmol Vis Sci 61(8):20 |
| abstractText | Purpose: This study is to investigate the corneal anomaly caused by excess transforming growth factor-alpha (TGF-alpha) during mouse development. Methods: Bitransgenic KeraRT/TGF-alpha mice, generated via cross-mating tetO-TGF-alpha and KeraRT mice, were induced to overexpress TGF-alpha by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-alphaECK mice (TGF-alpha excess expression by corneal keratocytes). Mouse eyes were examined by hematoxylin and eosin staining, immunofluorescent staining and transmission electron microscopy. Protein and RNA from mouse cornea were subjected to western blotting and real-time quantitative polymerase chain reaction. Results: In TGF-alphaECK mice, TGF-alpha overexpression resulted in corneal opacity. Excess TGF-alpha initially caused corneal epithelial hyperplasia and subsequent epithelium degeneration as the mouse developed, which was accompanied by gradually diminished K12 expression from the periphery of corneal epithelium and increased K13 expression toward the corneal center. Interestingly, K14 was detected in all layers of corneal epithelium of TGF-alphaECK mice, whereas it was limited at basal layer of controls. Transmission electron microscopy showed desmosome loss between corneal epithelial cells of TGF-alphaECK mice. In TGF-alphaECK mice, keratocan expression was abolished; alpha-SMA expression was increased while expression of Col1a1, Col1a2, and Col5a1 was diminished. Cell proliferation increased in the corneal epithelium and stroma, but not in the endothelium of TGF-alphaECK mice. Conclusions: Excess TGF-alpha had detrimental effects on corneal morphogenesis during mouse development in that it changed the cell fate of corneal epithelial cells to assume conjunctival phenotypic expression of K13, and keratocytes to myofibroblast phenotype. |
