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R.F. Gariano, D. Hu; Expression of VEGF, VEGF Receptors, and Neuropilins During Developmental Retinal Vascularization . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3261.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vascular endothelial growth factor (vegf) is critical for normal retinal vascular development, and may also participate in neuronal differentiation and survival during retinal development. In this study, we describe the spatial and temporal gene expression in mouse retina of vegf, its receptors (flt–1 and flk), and neuropilins 1 and 2 (np1 and np2, which function as vegf co–receptors) during the period of post–natal retinal vascularization. Methods: Retinal sections were obtained from C57B6 mice euthanized on the first day of life (P0), at P1, P3, P5, P7, P10, P12, P16, P18, P21, and P3 months. In situ hybridization was performed using probes for vegf–A, flk, flt–1, np1 and np2. Blood vessels were visualized using antisera to platelet endothelial cell adhesion molecule (PECAM). Sections were examined using light and fluorescence microscopy. Results: Already at P0, vegf expression is distributed across the entire extent of the nerve fiber layer (NFL), though blood vessels extend only a short distance from the optic nerve head at this time. During the first week of life, vegf expression appears in the neuroblastic layer, then intensifies in the central inner nucler layer (INL); both of these areas are avascular from P0 to P7. In contrast, expression of vegf receptors flk and flt–1 appears predominantly in the posterior vascularized NFL and ganglion cell layer (GCL) at birth, and gradually extends across the retina over the first week of life, roughly in step with the peripherally advancing vasculature. Expression of np1 and np2 is greater in the GCL than the NFL, and is more intense in the innermost than in the central INL. Conclusions: Expression of vegf in the superficial retina is relatively uniform during vascular development, and is not restricted to the leading edge of vascularization. In contrast, vegf receptors flk and flt–1 gradually extend from posterior to anterior in step with the advancing superficial vasculature. Expression of vegf co–receptors np1 and np2 is in part non–overlapping with that of flk and flt1. Our results suggest that during early post–natal retinal vascularization (1) vegf actions in the inner retina are constrained more by the temporal appearance of receptors than by the availability of vegf itself; and, (2) vegf likely interacts with distinct receptor types in anatomically segregated retinal (sub)laminae.
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