Adenovirus-Mediated Gene Transfer of vIL-10 in Experimental Corneal Transplantation

Abstract

Abstract: : Purpose: Gene transfer of immunomodulatory cytokines appears to be a promising approach in corneal transplantation. The EBV-encoded IL-10 homologue (vIL-10) has prominent anti-inflammatory potential and is able to modulate immune responses away from TH-1 towards TH-2. Therefore we determined whether (Ad)-mediated gene transfer of this cytokine has the ability to influence corneal graft rejection in a MHC I/II mismatched rat model. Methods: Corneal grafts from Lewis and Wistar-Furth rats were transduced ex vivo with 1x10₈ pfu of E1_-/E3_- Ad5CMVvIL-10 (n=8) or E1_- Ad5 dl 312 without transgene (n=8) and were transplanted into Lewis recipients. All allogeneic grafts were performed together with the syngeneic control. Nontransduced grafts (n=7) from Lewis and Wistar-Furth rats served as additional control. Results: All syngeneic grafts remained clear for the whole observation period. The mean survival time of Ad5CMVvIL-10 treated group (22.75±12.93 D) or Ad5dl312 treated group (22.86±8.03 D) was not significantly prolonged (p = 0.2583 and p = 0.1657 respectively) compared to untreated controls (17.43±4.2 D). Conclusion: vIL-10 in these experimental settings was not able to significantly delay graft rejection. Interestingly, transduction with the control-Ad did not accelerate but even showed the tendency to delay this process. Further studies will clarify the role of vIL-10 in allograft rejection.

Keywords: 607 transplantation • 419 gene transfer/gene therapy • 370 cornea: basic science