Cell transplantation approaches to retinal ganglion cell neuroprotection in glaucoma

Glaucoma is a complex neurodegenerative disease that involves interactions among multiple signaling pathways, ultimately leading to progressive retinal ganglion cell (RGC) death. The development of neuroprotective approaches to glaucoma therapy could preserve vision by modulating these pathologic pathways or by acting directly on RGCs to attenuate cell death and maintain function. Intraocular cell transplantation is being evaluated as one approach to achieve sustained RGC neuroprotection. Unlike traditional pharmacological approaches, transplanted cells might be capable of simultaneously targeting multiple pro-survival pathways via local delivery of secreted factors and/or via modulation of the intraocular microenvironment. Elucidating the mechanisms by which different cell types attenuate RGC death in models of glaucoma may uncover additional novel mechanisms of neuroprotection. In this review, we will discuss the rationale for transplantation-based approaches to neuroprotection for glaucoma and explore the various mechanisms of action proposed to account for RGC neuroprotection achieved by two distinct cell classes that have been studied most extensively for this purpose: glial cells and mesenchymal stem cells.