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 which form a major part of the retino-cortical pathway. Although there are some therapies available which primarily ameliorate the intraocular pressure (IOP), loss of sight often continues and thus illustrate the need for therapies which address the degeneration of the nervous system. Stem cell interventions have the unique potential to assist with the preservation and restoration of dysfunctional RGCs via direct cellular replacement, differential neuroprotection, and stimulating 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, for augmenting microenvironment cell preps. Some of the major challenges such as 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. 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, are forming the basis for developing first-of-its-kind regenerative therapies to restore vision in glaucoma patients, based on recent pre-clinical studies and ongoing early-phase clinical trials.
Chen et al. (2026) studied this question.