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1 From the Department of Immunology, Division of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London; and 2 Moorfields Eye Hospital, London, United Kingdom.
PURPOSE. To explore the potential for adenovirus-mediated ex vivo gene transfer of a soluble tumor necrosis factor (TNF) receptor and evaluate the effect of transplanting the adenovirally transplanted corneas in vivo.
METHODS. Rabbit corneal segments were transfected with replication-deficient adenovirus (AdTNFR) encoding a soluble TNF receptor fusion protein (TNFR-Ig). Production of TNFR-Ig was measured by using ELISA and bioassay. Corneas were transfected ex vivo with AdTNFR and then transplanted in vivo. Survival of AdTNFR-transfected corneas was compared with that of those treated either with a null vector control adenovirus (Ad0) or nontransfected control corneas.
RESULTS. Ex vivo production of a molecule with TNF blocking bioactivity from AdTNFR-transfected corneas was demonstrated over a period of 4 weeks. Transplanted AdTNFR-transfected corneas showed a marginally increased survival time in vivo over nontransfected control corneas, but a significantly increased survival time over Ad0-treated control corneas. Ad0 treatment of corneal allografts before transplantation had a proinflammatory effect and accelerated the onset of corneal endothelial rejection.
CONCLUSIONS. Adenoviral gene transfer is an effective means of transferring a gene encoding soluble TNFR-Ig to corneal endothelium, and ex vivo production of a biologically active secreted molecule was demonstrated for 4 weeks. However, in vivo, only a marginally increased survival was seen compared with control corneas. The introduction of this transgene using a less immunogenic vector may demonstrate prolongation of corneal allograft survival.
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