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Trevor J McGill, Shaomei Wang, Bin Lu, Stephen Huhn, Raymond D Lund, Alexandra Capela; Survival and efficacy of xenogeneic cell transplants in the RCS rat in the absence of immunosuppression. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2357.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related Macular Degeneration (AMD) is the primary cause of visual impairment in industrialized countries for which no cure is available. Transplantation of cells into the subretinal space (SRS) is a promising experimental neuroprotective treatment for dry AMD which is currently under clinical investigation. Although the normal SRS is considered to be relatively immunoprivileged, it is unclear how this privilege is affected by degeneration; therefore, ongoing clinical studies with allogeneic cells currently include immunosuppression. Preclinical studies in the RCS rat have demonstrated that, with the aid of continuous immunosuppression, donor xenogeneic cells survive transplantation, rescue photoreceptors and limit the associated loss of vision. The purpose of this study was to examine the survival and efficacy of human neural stem cells (HuCNS-SC) following transplantation under non continuous or even absent immunosuppression.
HuCNS-SC (1x105) were transplanted into the SRS of one eye of 38 RCS rats on post-natal day (P) 21. Thirteen (13) contralateral eyes served as medium-injected controls, and twenty-five (25) eyes were maintained as unoperated controls. The 38 animals were divided into four groups: no immunosuppression (Group A; n=8); two weeks of dexamethasone (DEX) (Group B; n=12); 2 weeks of DEX and 30 days of cyclosporine (Group C; n=11); and 2 weeks of DEX and continuous cyclosporine (Group D; n=7), the immunosuppression used in our previous preclinical studies. Visual acuity was measured through optokinetic tracking (OKR) at 30 day intervals. Retinal histology was performed following sacrifice at either P90 or P150.
OKRs were maintained in all cell treated eyes at all time points. Control eyes degenerated consistent with previously reported values. Surprisingly, transplanted cells survived in all groups despite the lack of immunosuppression in some animals. One animal in Group C exhibited graft rejection evident by a mononuclear response. Photoreceptor rescue was observed in all groups as evidenced by an outer nuclear layer thickness of 6-10 nuclei at both P90 and P150, consistent with our previously published data.
Our results demonstrate that xenogeneic HuCNS-SC can survive and rescue function in the RCS rat in the absence of immunosuppression.
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