Cyclosporine treatment of RPE allografts in the rabbit subretinal space

Purpose: To determine the effects of systemic cyclosporine A (CsA) on the s urvival of retinal pigment epithelial (RPE) allografts in the subretinal sp ace in an animal model using atraumatic transplantation surgery. Methods: Following pars plana vitrectomy, an RPE cell suspension from brown rabbits was injected with a glass micropipette into the subretinal space o f 39 albino rabbits. For immunosuppression, 22 rabbits were given an inject ion of CsA, 20 mg daily intramuscularly, 17 rabbits with RPE grafts were co ntrols. The grafts were monitored by biomicroscopy, color fundus photograph y, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 month s, respectively, and the eyes processed for light and electron microscopy i ncluding immunohistochemistry. Results: After three months, the transplanted RPE cells in both the CsA gro up and the controls, formed a monolayer in the subretinal space. Although a few macrophages were encountered, there was no massive cellular infiltrati on and the photoreceptor layer was well preserved. After six months, howeve r, there was a disruption of grafted RPE cells in both groups, characterize d by dispersion of melanin pigment in the subretinal space, and invasion of macrophages with focal photoreceptor damage but no infiltration of lymphoc ytes in the retina or choroid. No significant differences between the CsA t reated and the control eyes were discernible. Conclusion: Although the subretinal space has been considered an immunologi cally privileged site, we found that the survival of RPE allografts was lim ited. CsA did not prevent RPE allograft destruction in the subretinal space . The transplant seems to be disrupted either by immunological mechanisms t hat are not inhibited by CsA, or by nonimmunologic events.