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W. Zhuang, C. Park, M. Cano, V. Nguyen, K. Mori, R. Chuck, P. Gehlbach; Periocular Triamcinolone Increased Vector Traffic to Liver Following Adenovirus Mediated Ocular Gene Delivery. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5218.
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© ARVO (1962-2015); The Authors (2016-present)
Hepatic tropism of adenovirus vectors is one of the major drawbacks in adenovirus mediated gene delivery. Despite ocular feature of the blood ocular barrier, the adenovirus vector associated antigens are readily recognized by the systemic immune cells and develop both the humoral and cellular immune response. Although serious hepatic damage can be caused either by viral transfection into hepatocytes or by the transgene products, the hepatic tropism after intraocular delivery of adenovirus vectors is still unknown. In this study, we monitored the expression of the firefly luciferase reporter gene in the eyes of mice following intravitreous delivery of adenovirus vector.
Using an IVIS® 200 Imaging System, (Xenogen), we monitored the expression of the firefly luciferase reporter gene in the eyes of mice following intravitreous delivery of adenovirus vector.
We observed a significant luciferase expression in the liver area following intravitreous delivery of adenovirus vector and this luciferase expression was enhanced by local immunosuppression with periocular Triamcinolone Acetonide injection, which enhanced, at the same time, the intraocular luciferase expression. The luciferase expression in the liver was verified by the organ luciferase imaging. The liver luciferase expression means the viral escape from the eye across the blood ocular barriers. However, this hepatic viral uptake has no significant effect in time-expression curve of intraocular viral transgene (luciferase) both in the primary and the secondary administration of intravitreal adenovirus vectors. Finally, the hepatic viral uptake was rarely found in the secondary administration of intravitreal adenovirus vectors.
These results indicate that the local immune response (innate and acquired) is important to prevent the viral hepatic tropism from the eye.
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