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Y. Tsao, M. Tsai, P. Chou, C. Chang, R. Tsai, S. Chen; Suppression of Uveitis by Recombinant Adeno-Associated Virus Expressing Interleukin-1 Receptor Antagonist . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4590.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the potential of gene therapy with recombinant adeno-associated virus vector encoding interleukin-1 receptor antagonist ( rAAV-IL-1Ra) in the treatment of experimental uveitis. Methods: The Intravitreal cavity of New Zealand white rabbit was administrated with rAAV-IL-1Ra (1x107 infectious unit), and contralateral eye was injected with vehicle as control. Transgene expression was evaluated by immunohistochemistry stain and RT-PCR assay. At 10 and 100 days after rAAV-IL-1Ra injection, experimental uveitis was induced by 10ng IL-1αintravitreal injection. The therapeutic effect of rAAV-IL-1Ra on experimental uveitis was investigated with pathologic and aqueous analysis. Result: Following single injection of rAAV-IL-1Ra, the expression of human IL-1Ra gene was observed in rabbit eye for 100 days. The transgene expression can be found in various cell types such as ciliary epithelium, retinal ganglion cells and retinal pigmented epithelium, etc. Compared with control eyes, examination revealed that rAAV-IL-1Ra not only ameliorated experimental uveitis at 10 days but also suppressed delay uveitis episode at 100 days after rAAV-IL-1Ra injection. Conclusion: Intravitreal injection with rAAV-IL-1Ra lead to sustain human IL-1-Ra transgene expression in rabbit eye at least for 100 days. The transgene expression suppressed experimental uveitis and delay episode at both 10 and 100 days after rAAV-IL-1Ra injection. Long-term suppression of experimental uveitis would be achieved by gene therapy with single injection of rAAV- IL1Ra.
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