We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent 
for neuroprotective treatment in the retina, after screening 41 materials for 
anti-oxidative properties in a primary retinal cell culture under oxidative 
stress. We found that the intravitreal injection of hesperidin in mice prevented 
reductions in markers of the retinal ganglion cells (RGCs) and RGC death after 
N-methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also 
reduced calpain activation, reactive oxygen species generation and TNF-α gene 
expression. Finally, hesperidin treatment improved electrophysiological 
function, measured with visual evoked potential, and visual function, measured 
with optomotry. Thus, we found that hesperidin suppressed a number of cytotoxic 
factors associated with NMDA-induced cell death signaling, such as oxidative 
stress, over-activation of calpain, and inflammation, thereby protecting the 
RGCs in mice. Therefore, hesperidin may have potential as a therapeutic 
supplement for protecting the retina against the damage associated with 
excitotoxic injury, such as occurs in glaucoma and diabetic retinopathy.