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W.–H. Xiao, R. Abakah, J.D. Ash, S.A. Vinores; VEGF and PDGFs Have Unique Effects on Ocular Vascular Development in Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1908.
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Purpose: To perform a molecular and ultrastructural evaluation of the development of neovascular structures surrounding the lens and in the inner retina of transgenic mice overexpressing VEGF, PDGF–A, or PDGF–B in the lens. Methods: Electron and light microscopy was performed on neonatal eyes from transgenic mice to examine the newly formed vessels. Tissues and sections were stained for Griffonia simplicifolia isolectin–B4, glial fibrillary acidic protein, smooth muscle actin, VEGF, or albumin. Results: Each of the transgenic lines demonstrated marked changes in lens and retinal vasculatures. Perilenticular vessels in VEGF transgenics were not stable and did not develop substantial basement membranes. Many of the vascular endothelial cells had numerous microprocesses on the luminal and abluminal surface. Many of the vascular lumens were separated by a single cell with no surrounding basement membrane, which appeared to be anchored to the vessels by pseudopod–like processes from the vascular endothelial cells. While some of the vessels contained tight junctions, others were fenestrated. PDGF–A expression caused the accumulation of small intact vessels around the posterior of the lens. However, PDGF–B expression caused the accumulation of dense matrix around the lens, which contained blood vessels with a much larger diameter than normal. Vessels beneath the inner limiting membrane in all three transgenic lines generally had thicker walls and, although some tight junctions appeared to be at least partially open with accompanying leakage into the inner retina, fenestrations were absent. Interactions between endothelial cells and astrocytes, whether in the retina or in an epiretinal cell mass, usually resulted in well–formed interendothelial cell tight junctions. Conclusions: Overexpression of VEGF, PDGF–A, or PDGF–B results in marked changes in the perilenticular vessels. Each caused different effects in vascular structures, demonstrating that each serves a unique role in ocular vascular development. VEGF clearly plays a role in proliferation and angiogenesis while PDGF–A and B appear to promote vascular differentiation and stabilization, and may coordinate vessel size through recruitment of astrocytes and smooth muscle cells.
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