Therefore multiple clinical trials have used optic neuritis to test neuroprotective therapy.21 The rodent experimental autoimmune encephalomyelitis (EAE) model replicates many clinical symptoms and pathological signs of MS, including optic neuritis and significant RGC soma and axon loss.22, 23 In the present studies we take advantage of the accessible structures and clear functional readout of the EAE/optic neuritis model, and demonstrate that manipulating these two UPR pathways, PERK-CHOP pathway and IRE1α-XBP-1 pathway, provides neuroprotection and preservation of visual function. This evidence concerns the gene ERN1 and optic neuritis.