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J. Yang, U. Pleyer, H. Dannowski, K. Vogt, M. Hempel, T. Ritter; Effects of Adenovirus-mediated Gene Transfer of IL-12p40 on Corneal Allograft Survival . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4656.
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Purpose: Genetic manipulation of the donor cornea ex-vivo prior to transplantation may allow modulation of the allogeneic immune response. In this study we have investigated the effects of adenovirus-mediated gene transfer of IL-12p40 on the outcome in a rat experimental keratoplasty model. Methods: Transduction of Wistar-Furth rat corneas was performed using E1/E3 deleted adenoviral vectors transferring the gene for rat IL-12p40 (AdrIL-12p40). Following transduction with AdrIL-12p40 (2x108 pfu/ml) in DMEM/2%FCS for 3 hours and further 3 hours incubation in fresh medium, donor corneas were transplanted in MHC-class I/II incompatible Lewis rats. Thirteen Lewis recipients were randomly assigned to receive either AdIL-12p40 transduced grafts (n=7) or non-transduced grafts as controls (n=6). The survival of corneal allografts and intragraft mRNA-expression of CD3, CD25, IFN-γ, TNF-α, IL-10, and IL-4 were analysed after transplantation. Results: Corneal allografts without transduction (n=6) survived for 11.8±2.2 days. The transplantation of AdIL-12p40 treated corneal allografts resulted in a mean survival time of 10.6±2.0 days. No prolongation of corneal allograft survival could be found by gene-modified corneas. RT-PCR analysis showed that AdIL-12p40 group expressed lower intragraft CD3, CD25, IFN-γ, TNF-α, and IL-10 mRNA, but higher IL-4 mRNA at the day of rejection. However, all differences did not reach significance and could not prevent graft rejection. Conclusions: Ex vivo adenovirus-mediated IL-12p40 gene transfer to cultured corneas marginally reduced the infiltration of T cells to the allograft and Th1 cytokine release. New vectors with less immunogenicity and other immunoregulatory molecules will be considered in further investigations. CR: None Supported: DFG (Pl 150/10-1 + Ri 489/6-1)
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