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S.H. Yi, K. Terai, Y. Hayashi, W.W. Kao; Overexpression of TGF–ß1 by Periocular Mesenchymal Cells Perturbs Ocular Surface Tissue Morphogenesis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2179.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: We investigated the effect of excess transforming growth factor–ß1 (TGF–ß1) synthesized by migrating periocular mesenchymal cells on ocular surface tissue morphogenesis during development. Methods: Using tetracycline–inducible (Tet–Off) system, a Kera–tTA (keratocan promoter–tetracycline transcription activator) minigene containing 3.2 kb genomic DNA fragment 5’–flanking sequence, exon 1 and part of intron 1of Kera was used to prepare a Kera–tTA transgenic mouse line expressing tTA by migrating periocular mesenchymal cells during development. The Kera–tTA mice were mated with tetO–TGFß1 transgenic mice to produce Kera–tTA/tetO–TGFß1 bitransgenic mice. The experimental mice were fed normal diet, and doxycycline in water and chow to examine the effects of excess TGF–ß1 on ocular surface tissue morphogenesis by histology and immunofluorescence staining of keratins at postnatal days 12, 14, 3 weeks and 3 months. Results: Excess TGF–ß1 synthesized by mesenchymal cells resulted in malformation of eyelids. Histological examination revealed absent or underdeveloped Meibomian glands. Hyperkeratosis, angiogenesis and inflammation were also observed in central cornea in bitransgenic mice, and immunohistochemistry revealed absence of K12 and sporadic expression of K14. These phenotypes observed in bitransgenic mice were alleviated by feeding the experimental animals with doxycycline.Conclusions:TGF–ß1 overexpression causes eyelid abnormalities e.g., missing Meibomian glands and may also perturb corneal type epithelium differentiation signified by K12 expression in Kera–tTA/tetO–TGFß1 bitransgenic mice. It remains unknown, however, whether the abnormality of corneal epithelial defect is caused directly by excess TGF–ß1 or secondary to the abnormal eyelid.
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