Research progress on retinal ganglion cell damage induced by glaucoma and programmed cell death pathways

Glaucoma, the second leading cause of global blindness, has long posed a significant challenge to the medical community due to its treatment difficulties. The core pathological feature of glaucoma lies in the irreversible death of retinal ganglion cell (RGC), making the preservation of RGC a crucial strategy for preventing optic nerve damage. Recent research has unveiled the coexistence of multiple programmed cell death (PCD) pathways—apoptosis, necroptosis, pyroptosis, autophagic cell death, and ferroptosis—in RGC’ demise. Furthermore, blocking a single PCD pathway may not be enough to fully curb the RGC death process. In light of this, this review synthesizes the molecular mechanisms and interrelationships of various PCD pathways in RGC death under glaucomatous conditions, aiming to establish an integrated ” multi-modal cell death” framework. Based on the framework, it further argues for the potential value of jointly regulating multiple cell death pathways as an innovative therapeutic strategy for glaucoma.