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Y Ikeda, Y Yonemitsu, M Miyazaki, Y Goto, T Sakamoto, T Ishibashi, Y Ueda, M Hasegawa, S Tobimatsu, K Sueishi; Simian Immunodeficiency Virus-Based Lentivirus Vector for Retinal Gene Transfer . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4624.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lentivirus vectors hold promise as a potential treatment modality for ocular diseases. However, the possible risks associated with the use of current human immunodeficiency virus-based vectors (HIV) slow their clinical application. We recently developed a novel lentivirus vector derived from the non-pathogenic simian immunodeficiency virus (SIVagm), to minimize these safety issues. Here, we evaluated it in the adult rat retina as a preclinical safety study. Methods: We used two titers (2.5x107 or 2.5x108 transducing units/ml) of recombinant SIVs encoding the E.coli lacZ gene, with nuclear localizing signal (SIV-NLS-lacZ) or the green fluorescent protein (SIV-GFP). These virus solutions were injected into subretinal space of adult male Wistar rats (7 weeks old). We assessed transgene expression, retinal function via electroretinogram (ERG) and histology over a 1-year period. Results: SIV efficiently transferred mainly to the retinal pigment epithelium. ERGs revealed a transient and dose-dependent impairment of the retinal functions, and this almost completely recovered by 30 days. Retinas with a low titer histologically showed no significant inflammatory reaction throughout the observation period, and also maintained the transgene expression over a 1-year period. In the retinas with a high titer, however, mononuclear cell infiltration persisted in the subretinal area, and the retina corresponded to the injected area finally underwent degeneration by around day 90. Conclusion: We propose that SIV-mediated stable gene transfer might be useful for ocular gene transfer, however, more attentions should be paid to a cautious effect in use of high titer lentivirus to retina.
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