Excess transforming growth factor-A changed the cell properties of corneal epithelium and stroma

Lingling Zhang, Yong Yuan, Lung Kun Yeh, Fei Dong, Jianhua Zhang, Yuka Okada, Winston W.Y. Kao, Chia Yang Liu, Yujin Zhang

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3 Scopus citations

Abstract

PURPOSE. This study is to investigate the corneal anomaly caused by excess transforming growth factor-A (TGF-A) during mouse development. METHODS. Bitransgenic KeraRT/TGF-A mice, generated via cross-mating tetO-TGF-A and KeraRT mice, were induced to overexpress TGF-A by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-AECK mice (TGF-A 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-AECK mice, TGF-A overexpression resulted in corneal opacity. Excess TGF-a 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-AECK mice, whereas it was limited at basal layer of controls. Transmission electron microscopy showed desmosome loss between corneal epithelial cells of TGF-AECK mice. In TGF-AECK mice, keratocan expression was abolished; a-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-AECK mice. CONCLUSIONS. Excess TGF-A 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.

Original languageEnglish (US)
Article number20
JournalInvestigative Ophthalmology and Visual Science
Volume61
Issue number8
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
Supported by Grants from the National Institutes of Health/National Eye Institute (NIH/NEI) R01 EY23086, EY27901 (to CYL).

Publisher Copyright:
© 2020 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.

Keywords

  • TGF-A
  • corneal epithelium
  • hyperplasia
  • stroma
  • transgenic mouse

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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