Stem Cell-Based Interventions for Retinal Ganglion Cell Protection and Regeneration in Glaucoma: A Review of Current Evidence and Future Directions.

BACKGROUND: Glaucoma is one of the leading causes of irreversible blindness due to the ongoing loss of retinal ganglion cells (RGCs) and degeneration of the axons that form a major part of the retino-cortical pathway. Although there are some therapies available that primarily ameliorate the intraocular pressure, loss of sight often continues, and thus illustrates the need for therapies that address the degeneration of the nervous system.

SUMMARY: Stem cell interventions have the unique potential to assist with the preservation and restoration of dysfunctional RGCs via direct cellular replacement, differential neuroprotection, and stimulation of endogenous repair mechanisms. The focus of this review is on the most contemporary innovations which utilize stem cells to preserve and regenerate RGCs, which are vitally important for sight. The review addresses some of the newer cell source and cell prep technologies, particularly those using disorganized retinal microenvironment cell preps. Retinal microenvironment cell preps have resulted in some novel microenvironment cells designed to sequester stem cell grafts, to improve stem cell microenvironment cell preps, and to augment microenvironment cell preps. Some of the major challenges are reconstructing and integrating the lost retino-tectal and retino-collateral synapses in the visual pathway and the axonal outgrowth to and targeting appropriate central visual synaptic areas.

KEY MESSAGES: Some major challenges are safety, RGC immunochemistry and cell type diversity, and scalable cell prep technologies. This review encapsulates how stem cell biology, along with other technologies like gene editing and tissue engineering, is forming the basis for developing first-of-its-kind regenerative therapies to restore vision in glaucoma patients, based on recent preclinical studies and ongoing early-phase clinical trials.