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M.V. Emerson, T.J. McFarland, Y. Zhang, A.C. Westfall, B. Appukuttan, J.T. Stout; Effect of the Soluble VEGF Receptors sKDR and sNRP–1 on Retinal Vascular Integrity in a Rabbit Model of Vascular Permeability . Invest. Ophthalmol. Vis. Sci. 2006;47(13):830.
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Vascular endothelial growth factor (VEGF) is a specific and potent mitogen for vascular endothelial cells, leading to retinal edema and neovascularization. We sought to determine whether lentiviral–mediated transduction using the soluble VEGF receptor 2 (sKDR) and/or soluble neuropilin–1 (sNRP–1) genes perturbed VEGF–induced retinal vascular incompetence.
Lentiviral vectors containing the genes sKDR, sNRP–1, or both were injected into the vitreous cavity of New Zealand red rabbits. Control eyes received either no injection, phosphate buffered saline (PBS) or a lentiviral vector containing the green fluorescent protein gene. Animals (n=16) were divided into 2 groups; group I received intravitreal injections of VEGF165 at day 5,10, and 14–post viral treatment while group II received injections at day 6 and 11. Fluorescein angiography was performed after each VEGF injection and was evaluated for the presence of leakage as an indicator of vascular incompetence. Angiographic leakage was graded on a scale of 0 (none) to 3 (severe).
Analysis of groups I and II combined indicate that all treated eyes showed a reduction in vascular leakage at the second FA when compared to the first FA time point. The sKDR treated eyes showed less vascular leakage then sNRP–1 treated eyes. However, dual treatment with sNRP–1 and sKDR exhibited greater vascular permeability than either soluble receptor alone. The 3rd FA data demonstrated a slight increase in leakage in comparison to the 2nd FA, but severity of leakage was still less than observed at the initial time–point.
Lentiviral meditated transfer of sNRP–1 and sKDR together is not as effective as introduction of either soluble receptor alone in reducing vascular permeability. Determination of why a cooperative inhibition is not observed is of interest. Gene transfer of sKDR or sNRP–1 alone through a lentiviral vector system may be useful for inhibiting retinal edema.
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