Therapeutic strategies for glaucoma and optic neuropathies

• Published in: Molecular aspects of medicine Vol. 94; p. 101219
• Main Authors: Lo, Jung, Mehta, Kamakshi, Dhillon, Armaan, Huang, Yu-Kai, Luo, Ziming, Nam, Mi-Hyun, Al Diri, Issam, Chang, Kun-Che
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2023
• Subjects: Animals; Cell replacement; Disease Models, Animal; Disease Progression; Glaucoma; Glaucoma - drug therapy; Glaucoma - pathology; Humans; Intraocular pressure; Minimally invasive glaucoma surgery; Neurodegenerative Diseases - pathology; Optic Nerve Diseases - pathology; Optic Nerve Diseases - therapy; Optic nerve regeneration; Retinal ganglion cell development; Retinal Ganglion Cells - pathology; Retinal organoids; Stem cell; Glaucoma; Retinal organoids; Retinal ganglion cell development; Optic nerve regeneration; Stem cell; Cell replacement; Intraocular pressure; Minimally invasive glaucoma surgery
• ISSN: 0098-2997; 1872-9452
• DOI: 10.1016/j.mam.2023.101219

Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems. Glaucoma surgery has shifted to safer minimally invasive (or microinvasive) glaucoma surgery, but further trials are needed to validate long-term efficacy. Further, growing evidence shows that adeno-associated virus gene transduction and stem cell-based RGC replacement therapy hold potential to treat optic nerve fiber degeneration and glaucoma. However, better understanding of the regulatory mechanisms of RGC development is needed to provide insight into RGC differentiation from stem cells and help choose target genes for viral therapy. In this review, we overview current progress in RGC development research, optic nerve fiber regeneration, and human stem cell-derived RGC differentiation and transplantation. We also provide an outlook on perspectives and challenges in the field.