Abstract
Glaucoma, a leading cause of irreversible blindness worldwide, is a progressive optic neuropathy characterized by the apoptotic loss of retinal ganglion cells (RGCs) and elevated intraocular pressure. Current intraocular pressure-lowering therapies often fail to halt disease progression, creating an urgent need for neuroprotective and regenerative strategies. Stem cell therapy, leveraging the dual capabilities of differentiation and paracrine signaling, has emerged as a transformative approach for glaucomatous optic neuropathy. This review critically appraises recent advancements in stem cell-based interventions, focusing on three core therapeutic strategies: RGC regeneration, paracrine-mediated neuroprotection, and restoration of trabecular meshwork function for intraocular pressure regulation. We systematically synthesized evidence from preclinical and clinical studies, highlighting the efficacy of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cells in promoting retinal repair and neuroprotection. Despite promising results, significant translational challenges persist, including poor graft integration, tumorigenic risks, immune rejection, and the limitations of current animal models. We further discuss emerging technologies such as CRISPR/Cas9 gene editing and 3D bioprinting, which offer potential solutions for personalized and combinatory therapies. This review underscores that while stem cell therapy holds immense potential, overcoming these scientific and technical barriers is essential for its clinical translation into effective treatments for glaucoma.