Retinal diseases are seen as an important point of entry for CNS cell therapy because the retina is the most accessible part of the CNS, contains a relatively small number of cells, and outcomes of visual function can be accurately monitored. Devastating blinding disorders FXR agonist such as retinitis pigmentosa (RP) and the highly prevalent AMD lack effective treatments. Over the past decades, replacement of the outer photoreceptor cell layer and RPE with fetal tissue has demonstrated transient visual recovery in animal models and patients leading to clinical trials of human fetal tissue transplantation for these disorders (N. Radkte, Clinicaltrials.gov NCT00346060; S. Binder,

Clinicaltrials.gov NCT00401713).

Retinal stem cells (RSCs) have now been isolated from retina tissue and retinal cells Ribociclib nmr generated from hESCs. When transplanted, adult and ESC-derived retinal cells incorporate and rescue vision in animal models (Lamba et al., 2008, Wallace, 2011 and West et al., 2009). Although retinal replacement using RCSs has promise, human trials have not yet been initiated. HuCNS-SC transplanted into the subretinal space are being moved towards an IND application by StemCells. hESCs can be differentiated into RPE and transplantation of hESC-derived RPE cells (ESC-RPEs) preserves vision in animal models (Lu et al., 2009). Advanced Cell Technology, Inc. (ACT) received FDA authorization for studies using hESC-RPEs for Stargardt’s macular dystrophy in 2010 and for AMD in early 2011. Although

the primary defect in Stargardt’s appears in the photoreceptors, and secondary damage to the RPE underlies the rationale for replacing the RPE to improve cell function, support the photoreceptors, and delay retinal cell death. The AMD study will enroll 12 patients to address potential immunogenicity, tumorigenicity, and other safety issues for allogeneic hESC-RPE transplantation into retina. Cells will be injected as a suspension, and it remains to be seen whether they will incorporate into the existing RPE layer to form the polarized epithelium key for its normal function. Nevertheless, it is possible that a cell suspension could provide beneficial trophic factors even without epithelialization, although complications that are associated with RPE cell delamination, such as proliferative vitreoretinopathy, will be important to monitor. Related preclinicial work using hES-RPE is being developed by University College London in partnership with Pfizer’s London Project, at U.C. Santa Barbara in partnership with Geron under a CIRM disease team grant and at Hadassah Medical Center, Jerusalem in partnership with CellCure Neurosciences, Ltd. Tissue-derived stem cells and adult RPE progenitor cells offer expanded quantities of standardized cells for replacement of the RPE retinal layer.