Transplantation prospects for the inner retina

Abstract

Transplantation of stem or progenitor cells is an attractive new approach for treating neurodegenerative conditions of the central nervous system, which aims to protect or replace neurons and improve function. Proof of principle has already been shown in the retina that photoreceptors may be replaced by transplantation of neural progenitor cells. However, the task of retinal ganglion cell replacement is much more complex, as new cells will need to establish complex connections within the retina and also extend axons to precise targets in the brain. Although progress has been made in this field, it is likely that neuroprotective clinical applications will be established more quickly. Our laboratory has focused on the intraocular transplantation of cells to treat inner retinal disease, either by neuronal replacement or neuroprotection of existing cells. We have investigated the efficacy and effects of transplanting a variety of cell types, including human Mü ller stem cells (MIO-M1), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs) in a rat model of experimentally induced glaucoma. We also have developed and characterized a novel in vitro organotypic retinal explant culture system for exploring the methods of enhancing the efficacy of cell transplantation for the inner retina. In this review, we discuss the potentially beneficial effects of intraocular cell injections, identify current shortcomings of retinal stem cell therapy, and suggest directions for future research.

Photoreceptor-targeted gene delivery using intravitreally administered AAV vectors in dogs

“…15,16 The ILM acts as a barrier to transport of not only AAV, 31–33 but also stem cells 34 and nanoparticles. 35,36 To investigate this hypothesis, retinal sections labeled with anti-laminin antibody were used to measure ILM thickness.…”

Mesenchymal Stem Cell Transplantation for Retinal Degenerations and Dystrophies: Present and Future

“…The problem is due to remodeled retina, Muller glial seal and not permissive extracellular matrix for transplanted cells survival. This was shown in the work of Johnson and coworkers, who showed that after peeling of ILM with Muller cells neurits better integration and transdifferentiation rates were observed (Johnson et al, 2009). In animal models, highest levels of integration were observed in the models of retina laser injuries, which disrupt ILM (Castanheira et al, 2008;Wang et al, 2010a).…”

Cell-replacement therapy and neural repair in the retina

“…Interestingly, treatment with a glia-specific toxin dramatically improves cell integration (Johnson and Bull 2009).…”

“…This could be attributable to the adult retinal environment being unable to provide all signals needed for retinal neuronal development and even being inhibitory. About 1% of intraocularly transplanted cells commonly migrate into the retina (Johnson and Bull 2009;Johnson et al 2010aJohnson et al , 2010b. Intravitreally grafted cells outline the surface of the inner limiting membrane without penetrating the host retina (Johnson and Martin 2008;Johnson et al 2010aJohnson et al , 2010b.…”