97th DOG Annual Meeting 1999

K89

OUTCOME OF INTERLEUKIN-4 GENTRANSFER IN EXPERIMENTAL KERATOPLASTY

U. Pleyer, T. Ritter*, E. Bertelmann, B. Hinz


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 effect of adenovirus-mediated gene transfer of the Th2-cytokine Interleukin-4 (IL-4) to rat corneas in an experimental keratoplasty model.

Methods: Ex-vivo manipulation of Wistar-Furth rat corneas was performed using E1/E3 deleted adenoviral vectors transferring the gene for rat IL-4 (AdrIL-4) under control of the CMV-promoter. Following transfection with AdrIL-4 (2x108 pfu) in DMEM/2%FCS for 3 hours, donor corneas were transplanted in MHC-class I/II incompatible Lewis rats. Forty-eight Lewis rats were randomly assigned to receive either nontransfected grafts (n=29), Adr-IL4 transfected grafts (n=7), or syngeneic grafts (n=12).

Results: The mean survival time as well as the rejection rate of AdrIL-4 transfected grafts did not differ from untreated controls.

Group

Mean survival time (days)

Rejection rate (%)

Untreated

14.1 ± 3.8

62.9

Adr-IL4

12.6 ± 4.5

85.7

Syngeneic

> 60

0

p-value

p> 0.05

p> 0.05



Conclusions: Our results indicate that transplantation of AdrIL-4 transfected grafts neither reduced the rejection rate nor prolonged the mean survival time in an experimental keratoplasty model. Further investigations are necessary to identifie the reasons for failure and more efficient modulatory approaches.

Department of Ophthalmology and Instit. of Medical Immunology*, Charité, Humboldt University, Berlin. Supported: DFG (Pl 150/9-1 + Vo 489/6-1).


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