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K. Anzai, P.L. Gehlbach, M. Shibuya, S. Yoneya, L.L. Wei, K. Mori; Both Laser Photocoagulation and Photodynamic Therapy Enhance Gene Transfer in the Rat Retina Mediated by Adenoviral Vector . Invest. Ophthalmol. Vis. Sci. 2003;44(13):439.
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Purpose: We have previously demonstrated that intraocular injection of adenoviral vectors expressing pigment epithelium-derived factor inhibit and regress intraocular neovascularization (Mori K, et al. JCP 2001, IOVS 2002). A phase I clinical trial of this viral vector is now underway for intraocular neovascularization. The purpose of this study is to determine transduction efficiency of reporter gene in the retina treated by laser photocoagulation (PC) and photodynamic therapy (PDT), which are already established for the treatment of retinal and/or choroidal neovascularization. Methods: Lewis rats received no treatment, fundus PC with 532 nm diode laser or PDT using the hydrophilic photosensitizer; NPe6. On day 1, 3, 7 and 28 after the treatment 3x109 particles of adenoviral vector containing the expression construct of ß-galactosidase (AdZ.11D) was injected intravitreously. Eyes were enucleated 3 days after viral injection and processed for histochemistry. Results: In eyes with no treatment there was moderate to intensive staining for lacZ in the anterior segment but little in the retina. In eyes with PC and PDT treatments there were much greater lacZ stainings in the retina. The stained areas corresponded to the treated sites with PC and PDT. The lacZ expression peaked at day 3 in both PC and PDT model and sustained longer than untreated retina. Conclusions: Compared with untreated eyes, eyes with PC and PDT increased and sustained transduction in the area of the treatment. This indicates that intravitreous injection of adenoviral vector with expression cassette of anti-angiogenic constructs may provide a new promising strategy not only with a single use but in combination with PC or PDT treatments.
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