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Qinghang Meng, Maureen Mongan, Jinling Zhang, Ying Xia; Congenital eye defects due to failure of embryonic eyelid closure. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3063.
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Mammalian eye development involves a transient closure and re-opening of the eyelid. In humans, the upper and lower eyelids fuse to each other at week 9-12 and they separate at 4-6 months post fertilization. In mice, the eyelid development undergoes a similar process. The mouse eyelid closes at embryonic day (E) E15-E16.5, but different from the humans, the mouse eyelids remain closed at birth and its re-openning takes place at postnatal day 12-14. Failure of eyelid closure in mice leads to an eye-open at birth (EOB) phenotype. We used genetic mutant mice with the EOB phenotype as models to evaluate whether failure of embryonic eyelid closure is associated with congenital eye diseases.
Three mouse strains that displayed the EOB phenotypes were used for this study. One is the Map3k1ΔKD/ΔKD mice, which expressed a kinase-dead mitogen-activated protein kinase kinase kinase 1 (MAP3K1). Two is the Dkk2 knockout mice, which lack the Wnt inhibitor DKK2. Three is the c-JunΔOSE/ΔOSE mice, in which the transcription factor c-Jun is ablated only in ocular surface epithelium by crossing c-Jun flox and lens epithelium (Le)-cre mice. The eyes of wild type and knockout mice were collected at the prenatal pre-eyelid closure (E15.5) and post-eyelid closure (E16.5-E18.5) stages, and the postnatal pre-eye open (p1-p12) and post-eyelid open (after p14) stages. These eyes were subjected to histology and immunohistochemistry analyses.
Besides the eyelid closure defect, all the knockout mice had aberrant extraocular muscles (EOM). In addition, theMap3k1ΔKD/ΔKD and c-JunΔOSE/ΔOSE mice displayed smaller lens, while the Dkk2-null mice did not.
Studies in the mouse models suggest that failure of eyelid closure may be responsible for congenital defects of extraocular muscle, and MAP3K1 and c-Jun may have additional roles in lens development.
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