Replacement of the RPE monolayer

Abstract

There are numerous scenarios in which replacing the diseased RPE monolayer is an attractive but as yet unrealised goal. The proof of concept that vision can be improved by placing a healthy neuroretina onto a different, healthy, underlying RPE layer is demonstrated in patch graft transplantations. The surgical procedure to relocate the neuroretina is both complex and is hampered by postoperative complications and as such newer replacement procedures are also being investigated including stem cell replacement therapies. Past studies have largely focused on using cell suspensions and have had disappointing outcomes largely due to the lack of control over cellular differentiation, incomplete attachment onto Bruch's membrane and subsequent integration into the existing RPE monolayer. The choice of which cells to transplant is still under investigation and is complicated by factors such as the ease of collection of an adequate sample, rejection following implantation, the age of the cells and ethical issues. In all these situations, however, understanding the mechanisms of cellular differentiation are likely to be prerequisite to future successes. The current research into replacing the RPE monolayer is briefly discussed with reference to our experiences comparing IPE and RPE cells in an in vitro environment.

Expanded polytetrafluoroethylene as a substrate for retinal pigment epithelial cell growth and transplantation in age-related macular degeneration

“…This is important when considering which would be the appropriate cell type to eventually transplant. It would be essential to ascertain whether the candidate cell types such as genetically modified RPE cell lines, primary RPE or IPE, or RPE derived from stem cells, would still be able to phagocytose POS and maintain visual function and how the subretinal environment may influence this in vivo 4 28…”

“…For transplants to be successful they will need to be introduced under the macula as an intact functioning monolayer because delivery of isolated cells can cause serious complications, including proliferative vitreoretinopathy (PVR) 5. A range of biological substrates and degradable synthetic substrates have been investigated, but are of limited use due to lack of reproducibility of the biological substrates or the potential to leave cells exposed to underlying damaged Bruch's membrane following degradation, as well as the unknown fate of the degradation products 4 6–8…”

Optimization of Storage Temperature for Cultured ARPE-19 Cells

“…With the demonstration of long-term survival of RPE cell transplants both in various animal models and in humans [8–13], transplantation offers the prospect of a single intervention cure. The transplantation of RPE grafts enables appropriate implantation and orientation of an organized RPE cell layer in the retina [5, 14, 15] and circumvents several of the complications associated with the use of RPE cell suspensions [6, 8, 15, 16]. …”

Chirurgie der altersbedingten Makuladegeneration – Ist das im Zeitalter der Pharmakotherapie noch eine Option?

“…Zusammenfassend zeigen die präklinischen Studien, dass eine Implantation in den Subretinalraum zumindest bei der neovaskulären AMD möglich ist, Pigmentzellen auf Substraten kolonisierbar und implantierbar sind und funktionell gleichwertige retinale Pigmentepithelzellen aus Vorläuferzellen kultiviert werden können. Problematisch ist die Frage der Nutzung von Stammzellen [26] aber auch die der Implantation in den Subretinalraum eines erkrankten Auges mit bereits fortgeschrittenen degenerativen Veränderungen [32]. Erste klinische Studien zur Transplantation von Pigmentepithelzellen wurden über IPE-Zelltransplantationen publiziert [33,34].…”