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  • Title: Baculovirus is an efficient vector for the transduction of the eye: comparison of baculovirus- and adenovirus-mediated intravitreal vascular endothelial growth factor D gene transfer in the rabbit eye.
    Author: Kinnunen K, Kalesnykas G, Mähönen AJ, Laidinen S, Holma L, Heikura T, Airenne K, Uusitalo H, Ylä-Herttuala S.
    Journal: J Gene Med; 2009 May; 11(5):382-9. PubMed ID: 19263462.
    Abstract:
    BACKGROUND: The present study aimed to determine the efficiency and safety of baculovirus-mediated intravitreal gene transfer in rabbit eye and to compare its efficiency with adenovirus. We also studied how an intravitreal injection of vectors producing vascular endothelial growth factor D (VEGF-D) impacts the vasculature of rabbit eye. METHODS: Baculoviral (BacVEGF-D) or adenoviral VEGF-D (AdVEGF-D) were administered intravitreally into the right eye at different doses (10(8), 10(9) and 10(10) IU/ml) to 24 animals. Left eyes were injected with control viruses. To determine how long transgene expression lasted, we injected BacVEGF-D or BacLacZ to the vitreous humour of 11 animals and followed them for 4 weeks. Vitreous samples were taken after sacrifice for enzyme-linked immunosorbent assays and eyes were removed and fixed for histological analyses. RESULTS: Both baculoviruses and adenoviruses caused efficient expression of VEGF-D in the rabbit eyes. BacVEGF-D caused a dose-dependent vascular leakage and a moderate dilation of the capillaries. The highest effect was seen 6 days after gene transfer and was detectable for 2 weeks. Intravitreal injection of baculovirus caused expression of VEGF-D in the inner retina, photoreceptor cells and in retinal pigment epithelium cells, whereas adenovirus-mediated VEGF-D expression was detected in the nerve fiber layer and ganglion cell layer. Baculovirus caused a transient inflammation similar to adenoviruses. CONCLUSIONS: The study suggests that baculoviruses are efficient vectors for ocular gene transfer, especially if deeper retinal layers need to be transduced. In addition, intravitreal VEGF-D gene transfer caused blood-retina barrier breakdown but not neovessel formation in the rabbit eye.
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