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F. Wang, G. Shi, K.G. Rendahl, W.C. Manning, A. Jafari, W. Liu, M. Coyne, S.S. Miller; Inhibition of Choroidal Neovascularization (CNV) by Adeno-associated Virus (AAV) Mediated Expression of PEDF . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3580.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the anti-angiogenic activity of PEDF overexpressed in retinal pigment epithelium (RPE) using an AAV vector with a CMV promoter (AAV-CMV-PEDF) in a rat model of CNV induced by AAV-VEGF. Methods: PEDF was cloned by RT-PCR based techniques from native human fetal RPE cells and packaged into AAV by a triple transfection protocol. AAV-VEGF+AAV-PEDF were co-injected into the subretinal space (SRS) of one eye and AAV-VEGF+AAV-GFP were injected into the SRS of the contralateral eye of Sprague Dawley rats (1010-1011 particles in 2 µl). Pathologic changes in the retina were evaluated by histology and quantified by measuring area of CNV on serial sections (every 48 µm). Results: Three months after injection, quantification of CNV was made using histological sections. The extent of neovascularization in the AAV-PEDF+AAV-VEGF injected eye was 66±17% (mean±SD, p<0.05, n=4) smaller than that in AAV-GFP+AAV-VEGF injected eye. Conclusions: Preliminary results, in this model, show that AAV mediated overexpression of PEDF in RPE can inhibit the development of CNV, suggesting that AAV- PEDF potentially could be used to inhibit CNV associated with the "wet" form of age-related macular degeneration (AMD). Previous experiments also showed that sFlt1 was even more effective, in this model, in blocking VEGF-induced CNV suggesting multiple pathways of therapeutic intervention.
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