We recently reported that the apoptosis signal-regulating kinase-1 (ASK1)-p38 pathway is involved in ONI-induced RGC death.22 ASK1 has key roles in human diseases closely related to dysfunction of cellular responses to oxidative stress and endoplasmic reticulum stressors, including neurodegenerative diseases.14, 25 As spermidine possesses anti-oxidant properties, we examined whether spermidine modulates the ASK1-p38 pathway. This evidence concerns the gene MAP3K5 and neurodegenerative disease.