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K.C. Behling, A. Kuroki, J. Fosnot, S.J. Reich, A.M. Maguire, M.J. Tolentino, J. Bennett; Adeno-associated Delivery of TIMP-3 Inhibits Experimental Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1425.
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Purpose: These experiments aim to determine if AAV2/1-mediated delivery of tissue inhibitor of metalloproteinase-3 (TIMP3) can inhibit experimental laser induced choroidal neovascularization (CNV) in mice. Methods: AAV2/1-CMV-TIMP3 was delivered unilaterally to adult female C57BL/6 mice via subretinal injections. Contralateral eyes received subretinal injections of AAV2/1-CMV-LacZ and served as controls. Three weeks post-injection, mice underwent laser photocoagulation using an 810 nm diode laser (OcuLight Six; IRIS Medical, Mountain View, CA). Three laser spots were applied in both eyes. Two weeks after laser treatment, animals were perfused with high molecular weight FITC-Dextran, and choroidal flat mounts were prepared and analyzed microscopically. The area of CNV was measured with Openlab software (Improvision, Boston, MA) in a masked fashion. Results: Flat mount analysis revealed a statistically significant decrease in CNV in AAV2/1-CMV-TIMP3-treated eyes when compared to controls. Conclusion: AAV2/1-CMV-TIMP3 can reduce neovascularization in a murine model of laser induced CNV and may be a promising method of inhibiting CNV in humans.
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