Over-Expression of FGF7 Causes Sex Dependent Change in Eyelid Morphogenesis

Abstract

Purpose:: Dry eye is common in elder women. Numerous studies show the relationship of sex steroids and tear film function. However, little is known regarding molecular mechanism that accounts for such a hormone-dependency on tear film functions. A binary tet-off transgenic mouse model was used to examine the sex dependent role of FGF7 on skin, conjunctiva and meibomian gland morphogenesis.

Methods:: A 3.2 kb murine keratocan promoter (Kera3) was used to prepare Kera3- tetracycline transcription activator (tTA) and Kera3-ßGeo minigenes that were coinjected to fertilized eggs for preparation of transgenic mice. One of the Kera3-tTA-ßGeo mouse lines, Kera3-tTA-ßGeo3 was crossed with tet-O-FGF7 mice to produce Kera3-tTA-ßGeo3 /tet-O-FGF7 bitransgenic mice.

Results:: The ßGeo gene expression were observed in 2 (Kera3-tTA-ßGeo3 and Kera3-tTA-ßGeo4) of 6 transgenic founder lines in which both Kera3-tTA and Kera3-ßGeo were co-segregated in their offspring. ß-galactosidase positive cells was detected in developing stroma of Harderian, lacrimal and meibomian glands, and corneal stroma in both lines of Kera3-tTA-ßGeo3 /tet-O-FGF7 bitransgenic mice. About 5 % of female Kera3-tTA-ßGeo3 /tet-O-FGF7mice showed retarded growth. Bitransgenic male Kera3-tTA-ßGeo3 /tet-O-FGF7 and growth retarded female mice showed meibomian gland, sebaceous gland and eyelid epithelium hyperplasia and hair loss of the eyelid skin, but normal growth female Kera3-tTA-ßGeo3 /tet-O-FGF7 mice did not exhibit such phenotypical changes.

Conclusions:: Our results demonstrate that the sex steroids may collaborate with FGF7 in regulating homeostasis of conjunctiva, skin and meibomian gland epithelium.

Keywords: eyelid • cornea: tears/tear film/dry eye • differentiation