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Local Immunosuppression Prolongs Survival of RPE Xenografts Labeled by Retroviral Gene Transfer

From the ¹ Departments of Ophthalmology and ² Biochemistry and Molecular Biophysics, Columbia University, Howard Hughes Medical Institute, New York, New York; ³ The Jules Stein Eye Institute, University of California Los Angeles; and ⁴ Tufts New England Medical Center, Boston, Massachusetts; ⁵ Chang Gung Memorial Hospital, Taipei, Taiwan.

PURPOSE. To determine whether local immunosuppression with Cyclosporin A can influence the survival of human fetal retinal pigment epithelium (RPE) xenografts in the rabbit’s subretinal space.

METHODS. Cultured human fetal RPE cells were transduced with the gene for green fluorescent protein (GFP) using a lentiviral vector. The RPE was transplanted into the subretinal space of rabbits that received intravitreal cyclosporine either by weekly injections (0.25–0.5 mg) or by slow release (approximately 2 µg/d) from a capsule sutured into the vitreal cavity after prior cryopexy. The transplanted RPE was followed by GFP fluorescence scanning laser ophthalmoscopy and by histology of the transplant site.

RESULTS. RPE xenografts in eyes receiving intravitreal cyclosporine survived longer (several months) than they did in control eyes without cyclosporine. Survival was as long with slow release capsules as it was with weekly intravitreal injections at much higher concentrations of cyclosporine.

CONCLUSIONS. Local immunosuppression of the eye with cyclosporine prolongs the survival of RPE xenografts in the subretinal space of rabbits, implying that rejection involves activated T lymphocytes. Local immunosuppression with slow release capsules is as effective as weekly injections at much higher concentrations.

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