Survival of corneal allografts following adenovirus-mediated gene transfer of interleukin-4

Genetic manipulation of the donor cornea ex vivo prior to transplantation may allow modulation of the allogeneic immune response following penetrating keratopasty. In this study we investigated the effect of adenovirus-mediated gene transfer of the Th2 cytokine interleukin-4 (IL-4) to rat corneas in...

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Published in:Graefe's archive for clinical and experimental ophthalmology 2000-06, Vol.238 (6), p.531-536
Main Authors: PLEYER, U, BERTELMANN, E, RIECK, P, HARTMANN, C, VOLK, H.-D, RITTER, T
Format: Article
Language:English
Subjects:
Adenoviruses, Human - genetics
Animals
Biological and medical sciences
Corneal Transplantation
Female
Gene Transfer Techniques
Genetic Vectors
Graft Rejection - prevention & control
Graft Survival - genetics
Interleukin-4 - genetics
Medical sciences
Ophthalmology
Rats
Rats, Inbred Lew
Rats, Inbred WF
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the eye and orbit
Tissue Donors
Transplantation, Homologous
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Summary:Genetic manipulation of the donor cornea ex vivo prior to transplantation may allow modulation of the allogeneic immune response following penetrating keratopasty. In this study we investigated the effect of adenovirus-mediated gene transfer of the Th2 cytokine interleukin-4 (IL-4) to rat corneas in an experimental keratoplasty model. 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 (2 x 10(8) pfu) in DMEM/2% FCS for 3 h, donor corneas were transplanted in MHC class I/II-incompatible Lewis rats. Fifty-two Lewis rats were randomly assigned to receive either nontransfected grafts (n=32), AdrIL-4-transfected grafts (n=8), or syngeneic grafts (n=12). The rejection rate of AdrIL-4-transfected grafts (85.7%) could not be reduced as compared to controls (62.9%). In addition, the mean survival time of AdrIL-4-transfected grafts (12.6+/-4.5 days) did not differ (P>0.05) from that for untreated transplants (14.1+/-3.8 days). Our results indicate that overexpression of IL-4 is not sufficient to reduce the rejection rate of corneal allografts in an experimental keratoplasty model. Further investigations are necessary to identify the reasons for failure and establish more efficient modulatory approaches.
ISSN:0721-832X
1435-702X
DOI:10.1007/PL00007896