Role of FGF7 in Maintenance of Corneal Homeostasis

Abstract

Abstract: : Purpose:To elucidate the effects of excess FGF7 expression by corneal epithelium on corneal morphogenesis during embryonic development and in maintenance of homeostasis in adult. Methods: Bitransgenic Krt12^rtTA/rtTA/tetO–FGF7 and Krt12^rtTA/+/tetO–FGF7 mice were obtained by breeding Krt12^rtTA/rtTA and tetO–FGF7 mice. Single transgenic Krt12rtTA/rtTA, tetO–FGF7 mice were used as controls. The experimental animals were fed doxycycline in water and chow to induce the expression of FGF7 from conception or in adult for various periods of times. Histology and immunohistochemistry were used to evaluate the pathology caused by excess FGF7 synthesized by corneal epithelium. Results: Overexpression of tetO–FGF7 induced by doxycycline during embryonic development of resulted in the formation of vascularized cornea with epithelium hyperplasia in Krt12^rtTA/rtTA/tetO–FGF7 and Krt12^rtTA/+/tetO–FGF7 bitransgenic mice. Postnatal induction of FGF7 overexpression also leads to lesion in the cornea similar, albeit the pathological changes were not as severe to the findings of induction commenced during embryogenesis. Immunofluorescent staining revealed both keratin 12 and keratin 14 were expressed by all cell layers of corneal epithelium consistent with the keratin expression pattern found in corneal epithelium hyperplasia. Removal of doxycycline from the diet for 4 weeks following a 4 weeks induction the corneal epithelium hyperplasia reduced but small blood vessels could still be seen.Conclusions:Excess FGF7 synthesized by corneal epithelium of Krt12^rtTA/rtTA/tetO–FGF7 and Krt12^rtTA/+/tetO–FGF7 mice caused partially reversible pathological changes in corneas. The strategy of inducible overexpressing growth factors and/or cytokine is useful for studies of corneal cell biology in vivo.

Keywords: cornea: epithelium • growth factors/growth factor receptors • transgenics/knock-outs