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MI Dorrell, E Aguilar, R Summers, M Friedlander; Role of Astrocytes and R Cadherin During Neonatal Mouse Retinal Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1933.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A neonatal mouse model was used to study endothelial cell formation and migration during development of the retinal vasculature. Methods: Immunohistochemical analysis and transgenic mice using various endothelial cell markers and GFAP were used to study the interactions between endothelial cells and astrocytes during post-natal mouse retinal vascularization. Microarray gene expression analysis of mRNA from retinas at varying timepoints during retinal vascularization was also used to identify genes potentially involved in endothelial cell proliferation and migration. Subsequently, the biological relevance of selected gene products were tested in vivo by intravitreal injection of function blocking antibodies to selected molecules. Results: Endothelial cells were shown to migrate and form a vascular network on top of a complex astrocytic network in place at birth. Using fluorescently labeled lectin griffonia simplifolicia, we observed filapodia extending from the endothelial cells at the tips of the advancing vascular front during formation of both the superficial and deep vascular plexuses. During formation of the primary vascular network, the filapodia co-localize solely with the underlying astrocytes suggesting the astrocytes may provide a template for the newly developing vessels. Gene expression analysis determined R cadherin expression levels to be correlated with vascular development in the mouse retina. R cadherin protein levels also correlate spatially and temporally with vascularization of the superficial and deep retina vascular layers. Intravitreal injection of antibodies specific for R cadherin were found to disrupt the formation of the superficial vascular network and caused vessels to bypass the normal secondary vascular region and migrate into the photoreceptor layer during formation of the deeper plexus. Conclusion: Endothelial cells migrate from the optic nerve head during post-natal mouse retina development and form a vascular pattern determined by a pre-existing astrocytic template. The neuronal cell adhesion molecule R cadherin also plays a direct role in endothelial cell guidance and stabilization of the retinal vascular network.
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