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ON<\/jats:styled-content> pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells, and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE<\/jats:styled-content>) was utilized to study the onset and progression of ON<\/jats:styled-content> and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ<\/jats:styled-content> 1945. EAE<\/jats:styled-content> was actively induced in B10.PL<\/jats:styled-content> mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ<\/jats:styled-content> 1945 from Day 9 until sacrificing (Day 26). Visual function was determined by electroretinogram recordings and daily measurement of optokinetic responses (OKR<\/jats:styled-content>) to a changing pattern stimulus. Optic nerve and retinal histopathology was investigated by immunohistochemical and luxol fast blue staining. EAE<\/jats:styled-content> mice manifested losses in OKR<\/jats:styled-content> thresholds, a measurement of visual acuity, which began early in the disease course. There was a significant bias toward unilateral OKR<\/jats:styled-content> impairment among EAE<\/jats:styled-content>\u2010ON<\/jats:styled-content> eyes. Treatment with SNJ<\/jats:styled-content> 1945, initiated after the onset of OKR<\/jats:styled-content> threshold decline, improved visual acuity, pattern electroretinogram amplitudes, and paralysis, with attenuation of retinal ganglion cell death. Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of early, unilateral visual impairment in EAE<\/jats:styled-content>\u2010ON<\/jats:styled-content> parallels the clinical presentation of ON<\/jats:styled-content> exacerbations associated with multiple sclerosis. Calpain inhibition may represent an ideal candidate therapy for the preservation of vision in clinical ON<\/jats:styled-content>.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nAs in multiple sclerosis (MS) patients, optic neuritis (ON) and early, primarily monocular loss in spatial acuity is observed in a rodent model (EAE, experimental autoimmune encephalomyelitis). Daily oral treatment with the calpain inhibitor SNJ 1945 preserves visual acuity and preserves retinal ganglion cells (Brn3a, brain\u2010specific homeobox\/POU domain protein 3A) and their axons (MOSP, myelin oligodendrocyte\u2010specific protein). Calpain inhibition may represent a candidate therapy for the preservation of vision in ON.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13770","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T14:18:47Z","timestamp":1470925127000},"page":"270-284","source":"Crossref","is-referenced-by-count":15,"title":["Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis"],"prefix":"10.1111","volume":"139","author":[{"given":"Amena W.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Rohrer","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"},{"name":"Department of Ophthalmology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Alexion Pharmaceuticals Cheshire Connecticut USA"},{"name":"Department of Pathology, Microbiology, and Immunology University of South Carolina School of Medicine Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Wheless","sequence":"additional","affiliation":[{"name":"Medicine\u2013Division of Biostatistics and Epidemiology Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriti","family":"Samantaray","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swapan K.","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology University of South Carolina School of Medicine Columbia South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Inoue","sequence":"additional","affiliation":[{"name":"Senju Pharmaceutical Co Ltd Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Azuma","sequence":"additional","affiliation":[{"name":"Senju Pharmaceutical Co Ltd Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naren L.","family":"Banik","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Alexion Pharmaceuticals Cheshire Connecticut USA"},{"name":"Department of Neurology and Neurosurgery Medical University of South Carolina Charleston South Carolina USA"},{"name":"Research Service Ralph H. 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