Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.

Jing Li,Jing Li,Yu Qin,Yu Qin,Di Wu,Jiangyue Zhao,Xuefei He,Xinwei Wu,Xinwei Wu,Jia Liu,Jia Liu,Chastain Anderson,Shusheng Wang,Jinsong Zhang,Jinsong Zhang,Fangkun Zhao,Fangkun Zhao,Tudor C Badea

doi:10.1371/journal.pone.0159639

Abstract

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development.

Highlights

Microphthalmia, a common congenital ocular disease, is characterized by abormal small eyes with leukoma, cataract, aniridia, anterior and posterior synechiae, retinal detachment, retinal folds and so on
Smad4 in the lens ectoderm affects Sonic hedgehog (Shh) and Wnt signaling in the retina
Microphthalmia can be caused by lens dysplasia or failure of retinal differentiation in monogenic mutants [1]

Summary

Introduction

Microphthalmia, a common congenital ocular disease, is characterized by abormal small eyes with leukoma, cataract, aniridia, anterior and posterior synechiae, retinal detachment, retinal folds and so on. The estimated birth prevalence of this condition is 1 per 7000, but it was reported in 3.2–11.2% of blind children [1, 2]. Genetic causes account for approximately 80 percent of the disease [1]. The underlying cellular and molecular mechanism of microphthalmia pathogenesis remains unclear. The abnormality in the anterior segment of microphthalmia, such as leukoma, cataract and aniridia, can be relieved by cataract phacoemulsification combined intraocular lens implantation, keratoplasty and other surgical.

Methods

Results

Conclusion