The retinal pigment epithelium (RPE) lies in the back of the eye between the neural retina and its choroidal blood supply. This layer of epithelial cells serves to protect the health and integrity of the outer retina. In the choroid, abnormal blood vessel growth or choroidal neovascularization (CNV) occurs in diseases such as age related macular degeneration (AMD) - the major cause of blindness for people over the age of 60. Vascular endothelial growth factor (VEGF) and other pro- or anti-angiogenic factors are constitutively secreted by the RPE into the extracellular space on both sides of the epithelium. The effects of these molecules on RPE physiology are not known. Evidence from human pathologic specimens and from rodent models suggests that increased VEGF production by the RPE is the source of CNV. Research in this area is severely hampered by the lack of a small animal model in which VEGF secretion by the RPE induces CNV. In preliminary experiments, we have used gene transfer techniques to develop a rat model for stimulating blood vessel growth in the back of the eye. This model will be used to test the hypothesis that secretion of VEGF by RPE is critically important in generating choroidal neovascularization (CNV). Gene transfer techniques will be also used to inhibit or reduce this VEGF-induced abnormal blood vessel growth. These experiments should provide a deeper understanding of CNV and the basis for a potential therapy for diseases like AMD. Normally, there is a very close anatomical relationship between the RPE and the retina. Separation of these two tissues occurs in a whole host of pathologies that lead to the abnormal accumulation of fluid in the extracellular or subretinal space. This separation or retinal detachment can lead to a loss of vision. One of our goals is to develop a rat model of retinal detachment. This model will allow us evaluate putatively therapeutic molecules that work directly on the RPE to remove fluid from the subretinal space. This removal will restore the normal anatomical relationship between RPE and retina and should improve vision.
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