Sources of retinal pigment epithelium (RPE) for replacement therapy

Abstract

Stem cells, with their capacity to regenerate and replace diseased tissues, have recently been proposed as having great potential in the treatment of age-related macular degeneration (AMD). A stem cell therapeutic approach could operate to replace either the retinal pigment epithelium (RPE), the neurosensory retina or a combination of both. From the scientific perspective, RPE replacement alone is likely to be far more straightforward than rebuilding the complex circuitry of the neurosensory retina. Furthermore, recent advances with induced pluripotent stem cells have raised the real possibility of transplanting healthy 'young' autologous RPE into patients with early signs of AMD. At this stage, however, it is useful to reconsider some of the earlier clinical studies that used suspensions of autologous RPE cells harvested from the peripheral retina. These showed that isolated RPE cell suspensions had little capacity to recreate a monolayer on the diseased Bruch's membrane of AMD. To counter this problem, researchers from Southampton in the UK report the use of a synthetic polymer alternative to Bruch's membrane, which could provide a scaffold for future RPE derived from stem cells or possibly reopen opportunities for autologous RPE cells harvested from the peripheral retina.

A Novel Approach for Subretinal Implantation of Ultrathin Substrates Containing Stem Cell-Derived Retinal Pigment Epithelium Monolayer

“…Stem cells, with their capacity to differentiate and replace diseased cells, could be a good source for RPE cell transplantation [8,9]. In a normal retina, RPE cells maintain polarity and remain as a monolayer.…”

Eye Development and Retinogenesis

“…However, successive rounds of depletion of undifferentiated cells pretransplantation have been shown to greatly decrease this risk (Tucker et al 2011). Another challenge is the potential need to replace the damaged Bruch's membrane, the basement membrane of the RPE, to provide a scaffold for injected cells (Lee and Maclaren 2011).…”

Assessment of 180° Rotation of the Choroid as a Novel Surgical Treatment for Age-Related Macular Degeneration

“…The clinical translation of stem cell-related technologies in AMD is therefore dependent on developing a means of repairing or replacing the damaged subfoveal BM. 37 Against this background, we therefore sought to develop a novel surgical technique to incorporate some of the advantages of macular rotation and RPE-choroid graft surgery, but which might also provide a means of replacing submacular BM necessary for future ES/iPS cell approaches and reduce the potential for early ischemia. The technique involves rotating a full-thickness graft of choroid, BM, and RPE on a vascular pedicle such that healthy extramacular tissues are repositioned under the fovea.…”

“…Unless transplanted replacement RPE cells are able to bind to a suitable substrate, their survival and differentiation is shortlived, 44 which is a hurdle that will need to be overcome before clinical trials in this field of research. 37 BM with its pentilaminar structure, specific permeability properties, and an embryological origin involving two germ layers is a complex structure to regenerate from stem cells in vitro. Our results, however, suggest that autologous BM harvested from the temporal retina may provide a natural nonsynthetic alternative, and thus facilitate the application of stem cell approaches to RPE replacement.…”