Long-term Efficacy of Human Central Nervous System Stem Cells (HuCNS-SC) Transplanted into the Subretinal Space of RCS Rats

Abstract

Purpose: : To examine the long-term survival and distribution of HuCNS-SC after early transplantation into the subretinal space and correlate the effects on rescue of photoreceptors and prevention of visual dysfunction in the RCS rat.

Methods: : HuCNS-SCs were transplanted into the subretinal space of immunosuppressed RCS rats at P21. Optokinetic response thresholds (OKR) were measured using a virtual optomotor system at 30 day intervals beginning on P30. Histological examination of the retinas was performed by cross-section at P40, P60, P90, P200 and P250 and by whole mount preparations at P90.

Results: : All cell-engrafted eyes maintained OKR values near non-dystrophic levels with only a ~12% reduction noted at P250. OKR values measured in untreated and media-injected eyes deteriorated at rates similar to control RCS rats. Cross section histology at P40 and P90 revealed donor cells migrating in the subretinal space as a layer of spindle shaped cells between the host retina and RPE. Whole mount data at P90 confirmed this pattern of migration. Significant reduction of the debris zone in the area of the graft was also noted. Some retinas showed migration of human cells into the inner retina at P90 which became more prevalent at later time points. At the latest time point examined (P250), human cells persisted in the subretinal space but in lower concentration compared with earlier time points. Near normal levels of photoreceptor preservation was seen up to P90, but by P250, the photoreceptor layer was reduced to 4-5 rows of nuclei over a more localized area.

Keywords: transplantation • photoreceptors: visual performance • degenerations/dystrophies