Glaucoma is one of the major causes of irreversible blindness worldwide. The disease is characterized by the progressive loss of retinal ganglion cells (RGCs), and recent evidence supports a key role for oxidative stress in the pathogenesis. In this review, we systematically examine the mechanisms of oxidative stress in the pathogenesis of RGC injury, including impaired mitochondrial function, neuroinflammation, and complement system dysregulation, as well as increased intraocular pressure (IOP). We then evaluate currently available neuroprotective strategies targeting these pathways and highlight in particular direct antioxidant therapies and inhibition of specific enzymes in the oxidative stress pathways. We then discuss recent advances powered by new methods such as single-cell multi-omics. A notable gap exists between encouraging results in preclinical models and less success in clinical trials. This disconnect points to important new directions for future research.
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