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BJ Raisler, MA Grant, AM Timmers, V Chiodo, KI Berns, WW Hauswirth; AAV-mediated Expression of PEDF or Angiostatin (K1K3) Reduces Retinal Neovascularization in a Mouse Model of Ischemic Retinopathy . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1258.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the efficacy of recombinant adeno-associated viral (rAAV) mediated expression of pigment epithelium-derived factor (PEDF) or Kringle domains 1-3 (K1K3) of angiostatin in reducing aberrant microvessel formation in an mouse model of ischemia-induced neonatal retinal neovascularization (NV). Methods: Recombinant AAV vectors expressing the therapeutic genes of interest were injected into one eye of postnatal day 0 (P0) newborn mouse pups. Retinal NV was induced in P7 mice exposed to 73% +/- 2% oxygen for 5 days, followed by room air for another 5 days. Retinal NV was quantified by the number of endothelial cell nuclei above the inner limiting membrane in P17 eye sections. Protein levels for PEDF and K1K3 expression were measured by indirect sandwich ELISA for the time frame corresponding to the ischemia-induced model. Results: The number of vascular endothelial cell nuclei above the inner limiting membrane in eyes treated with rAAV-PEDF or rAAV-K1K3 was reduced to a significant level compared to paired control eyes based on a masked analysis. The protein levels measured by ELISA indicate expression of PEDF or K1K3 is detectable as early as 1 day post-injection and persists for the period of the experimental model at therapeutic levels. We hypothesize that the rapid early expression pattern is due, at least in part, to the mitotic nature of retinal cells at this developmental stage. Conclusion: : Expression of either PEDF or K1K3 from rAAV vectors reduces the level of retinal NV in this model of ischemic retinopathy. The protein levels detected by ELISA correlate well with the reduction in NV and confirm that short-term expression from rAAV vectors is a viable therapeutic method. These data suggest that rAAV-PEDF or rAAV-K1K3 may be therapeutically useful in the treatment of retinal or choroidal neovascular disease.
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