Retinal Ganglion Cell Death in Glaucoma: Advances and Caveats

Purpose: Retinal ganglion cell death occurs during the glaucoma pathological process, and it is significant because of the poor regeneration capacity of retinal ganglion cells. With a constantly increasing understanding of retinal cell death mechanisms, we now know that simply blocking a specific mechanism of cell death might not prevent retinal ganglion cell death. This review aimed to summarize the mechanisms of retinal cell death in glaucoma models and discuss the caveats in restoring visual function in these studies. Methods: A literature search was done on PubMed using key words including glaucoma, ocular hypertension, retinal ganglion cell, cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagic cell death, and parthanatos. The literature was reviewed to summarize the information about the lethal pathways of retinal ganglion cell in the glaucoma-like animal models. Results: Based on the purpose, 100 studies were selected and discussed in this review. Conclusions: The damage to ganglion cells in glaucoma-like animals can occur via multiple lethal pathways and the molecular mechanisms are still incompletely understood. Further investigations on the crosstalk between different cell death pathways and the common upstream regulators could augment the development of novel targeting agents for the curative treatment of glaucoma.