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Malia M. Edwards, D S. McLeod, Renzhong Li, Imran Bhutto, Rhonda Grebe, Xiuqian Mu, Gerard A. Lutty; Retinal Vascular Development Is Dependent On Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4840.
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To date, much of the research aimed at understanding murine retinal vascular development has focused on interactions between astrocytes and endothelial cells. The present study investigated the influence of ganglion cells on retinal vascular development utilizing Math5-/- (Atoh7tm1Gan) mice, which experience a 98% reduction in ganglion cells .
Math5-/- and littermate control mice were euthanized and enucleated eyes were fixed overnight. Immunohistochemistry and isolectin Griffonia simplicifolia isolectin IB4 (GS isolectin) labeling were performed on flatmount retinas to visualize astrocytes and blood vessel formation in the retina and vitreous.
While the control superficial vasculature was fully developed by P7, there were no vessels within the Math5-/- retina up to P9. A number of GS isolectin+ cells were present, however, throughout the retina. The astrocyte template resembled that of controls in the central retina at P4 but was sparse in the periphery. By P7, Math5-/- retinas contained more astrocytes than controls. At 3 weeks of age, the Math5-/- retina had developing capillary networks in both the inner retina and the nerve fiber layer despite lacking large arteries or veins within the primary plexus. In order to investigate whether the fetal vasculature of vitreous invaded the retina, the vitreous was left in place. Budding of the vasa hyaloidia propria was observed as early as P4 and progressed with age. While most of these developing vessels remain in the vitreous, filopodia could be seen extending into the retina and anastamosing with GS isolectin+ cells at P9. Interestingly, the resulting vascular networks, even when in the vitreous, form a cobblestone pattern similar to that observed in capillary networks within the wild type retina. In addition, GFAP+ cells, resembling astrocytes and Mueller cells, were seen associating with persistent fetal vasculature by P4.
Ganglion cells and their nerve fibers appear to be required for normal retinal vascular development. Persistent fetal vasculature can bud to capillary networks which are correctly placed within the retina.1. Wang, S.W., et al., Requirement for math5 in the development of retinal ganglion cells. Genes Dev, 2001. 15(1): p. 24-9.
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