The role of stem cells in Treatment of retinal ganglion cell axon degeneration

Abstract

As compared with other tissues, the retina has unique advantages as a target for cell-based therapies. The retina is an accessible tissue with modern vitreo-retinal surgical approaches refined for the transplantation of cells to specific locations in the retina. The immune privilege of the eye may reduce the rejection of transplanted cells and the numerous tools to measure ocular structure and function including optical coherence tomography (OCT), fluorescein angiography and multifocal electroretinography (ERG) allow for unparalleled structure–function correlation. These advantages have led retinal disorders to the forefront of clinical trials into cell-based trophic and regenerative therapies. Recent advances including the directed differentiation of stem cells to retinal cell types, the production of induced pluripotent stem cells and the creation of three dimensional in-vitro retinas should bring the application of this technology closer to reality. Both regenerative and trophic stem cell therapies for retinal disease are actively being investigated in multiple clinical trials with initial results demonstrating safety and possible visual acuity benefits. These advances have shown that stem cell therapy will be a useful treatment modality to restore vision in retinal disease. RGCs axons are typically compromised in glaucoma.The elevated pressure causes significant cell damage or in traumatic optic neuropathy where direct trauma or compression of the axons occurs, yielding in profound damage.Progression of cell damage is not uncommon,although enhanced modes of neuro-protection have been sought for many years.In recent years considerable effort has been directed at some type of cell based restoration of damaged RGCs.Reprogramming iPS cells to generate RGCs this is usually achieved via amultistep process ,moving first to neurons and then to more specialized RGCs.Differentiated induced pluripotent stem cells(iPSc) that became RGCs were used for intravitreal injection in mice. Effects on visual function and integration were assessed.Others have used subretinal injections to overcome integration obstacles. Mesenchymal stem cells have also been evaluated for RGC replacement. Their value is primarily the secretion of neuroprotective factors rather than differentiation into RGCs.However,in other cases there was some integration of these stem cells into ganglion cell layer suggesting potential for RGC replacement. An endogenous RSC population at the ciliary margin zone has been studied in some detail.Muller stem cell line has also been differentiated into RGCs.however,for clinical translation,endogenous retinal stem cells may be less useful than cells derived from more accessible sites,such as mesenchymal or iPSc.Some obstacles to immediate clinical use include availability of stem cells and difficulty in expanding it to numbers required for transplantation.