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D. Imai, S. Yoneya, K. Anzai, M. Ito, K. Mori; Upregulation of Coxsackie Adenovirus Receptor in the Retina with Ischemic Retinopathy. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3703.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Currently a phase I clinical trial of adenoviral vector is now underway for intraocular neovascularization. We have previously reported that retina with neovascularization (murine ischemic retinopathy model) increased transduction especially in the area of retinal neovascularization (Mori K, et al. IOVS 2002). This study is designed to demonstrate the mechanisms of enhanced gene transduction the retina with ischemic retinopathy. Methods: Five C57/BL6 mice at postnatal day (P)7 were placed in an incubator and exposed to 75% oxygen for 5 days. Oxygen was continuously monitored with an oxygen controller. Mice were returned to room air at P12. Five control mice were housed in the room air. Eyes were enucleated and total RNA was extracted at P12 and 17. Samples were processed for qRT–PCR (Prism 7700, Applied Biosystems) to quantify mRNA expression of coxsackie adenovirus receptor (CAR) and integrins αV, ß3 and ß5, which have been shown to play a role in cell surface interaction and internalization of viral vector during the transduction process. Results: Relative CAR expression level in control retina was 0.88±0.17 at P12 but decreased to 0 at P17. In contrast CAR expression was upregulated (1.46±0.41) at P12 in retina with ischemic retinopathy when compared to control. At P17 relative expression level of CAR was significantly higher (0.54±0.25) than control. There was no significant difference in relative expression levels of integrins αV, ß3 and ß5. Conclusions:CAR expression was upregulated in the retina with ischemic retinopathy. This, at least in part, may support our previous data demonstrating enhanced gene transduction by adenoviral vector in the retina with ischemic retinopathy.
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