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 Müller 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. [ABSTRACT FROM AUTHOR]