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Fei Dong, Chia-Yang Liu, Wei Li, Zuguo Liu, Yongxiong Chen, Winston W Y Kao; Postnatal Overexpression of TGFα in Eyelid Stroma Disturbs Eyelid Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4463.
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Growth factors play important roles in tissue morphogenesis during development and maintenance of homeostasis in adults. Epidermal growth factor receptor (EGFR) signaling has pivotal role in eye lid morphogenesis, perturbation of genes involved in the signaling pathways results in eye open at birth in mouse. Transforming Growth Factor alpha (TGFα) is one of the important ligands of EGFR, which has been found to have important roles on the eyelid morphogenesis. This study aims to examine the manifestation of excess TGFα in eyelid morphogenesis after birth.
: Bi-transgenic Kera-rtTA/tet-O-TGFα (KR/TGFα) mice were bred by crossing Kera-rtTA (keratocan promoter) and Tet-O-TGFα mice. The newborn KR/TGFα pups were induced to over express TGFα by eyelid stromal cells via feeding doxycycline chow to the nursing mother from P0 (postnatal day 0) through P15. Eyes were collected at various time points and subjected to histological and immunofluorescence staining.
Excess TGFα resulted in abnormalities in eyelid morphogenesis. The bi-transgenic mice displayed eyelid open around P10 and swollen eyelids. Single transgenic mice eye open around P14. Histology examination shows conjunctival epithelium thickening, increase of goblet cells, and malformation of Meibomian gland, formation of a cyst derived from lid stromal cells which leads to levator aponeurosis dysfunction, and mimicking human ptosis symptoms. Immunohistochemistry examination manifested high proliferation property (PCNA positive), low expression of differentiation markers e.g., collagenous matrix by Masson-trichrome staining of the levator aponeurosis. The cells of the the cyst are keratin negative and vimentin positive suggesting they are mesenchyme origin.
Taken together, these observations suggest that excess TGFα disrupts eyelid morphogenesis, especially the proper formation and function of the levator aponeurosis.
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