Jing Li1, Jin-Song Zhang2, Jiang-Yue Zhao3, Guo-Ge Han1. 1. Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Nankai University, Tianjin 300000, China. 2. Shenyang Aier Excellence Eye Hospital, Shenyang 110000, Liaoning Province, China. 3. Department of Ophthalmology, the Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory, Shenyang 110000, Liaoning Province, China.
Abstract
AIM: To investigate how signals from lens regulate retinal vascular development and neovascularization. METHODS: Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively. Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4 defective eye. cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype. Quantitative polymerase chain reaction (qPCR) was carried out to verify the microarrays results. RESULTS: We found that inactivation of Smad4 specifically on surface ectoderm leads to a variety of retinal vasculature anomalies. Microarray analyses and qPCR revealed that Sema3c, Sema3e, Nrp1, Tie1, Sox7, Sox17, and Sox18 are significantly affected in the knockout retinas at different developmental stages, suggesting that ocular surface ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina. CONCLUSION: Our data suggest that the cross-talk between ocular surface ectoderm and retina is important for retinal vasculature development, and Smad4 regulates various signaling associated with sprouting angiogenesis, vascular remodeling and maturation in the retina of mice. International Journal of Ophthalmology Press.
AIM: To investigate how signals from lens regulate retinal vascular development and neovascularization. METHODS: Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively. Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4defective eye. cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype. Quantitative polymerase chain reaction (qPCR) was carried out to verify the microarrays results. RESULTS: We found that inactivation of Smad4 specifically on surface ectoderm leads to a variety of retinal vasculature anomalies. Microarray analyses and qPCR revealed that Sema3c, Sema3e, Nrp1, Tie1, Sox7, Sox17, and Sox18 are significantly affected in the knockout retinas at different developmental stages, suggesting that ocular surface ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina. CONCLUSION: Our data suggest that the cross-talk between ocular surface ectoderm and retina is important for retinal vasculature development, and Smad4 regulates various signaling associated with sprouting angiogenesis, vascular remodeling and maturation in the retina of mice. International Journal of Ophthalmology Press.
Authors: Alexandra M Ochsenbein; Sinem Karaman; Steven T Proulx; Michaela Berchtold; Giorgia Jurisic; Esther T Stoeckli; Michael Detmar Journal: Development Date: 2016-02-15 Impact factor: 6.868