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Vision impairment is one of the major clinical features of MS. Previous studies from our lab have shown that MDL 72527, a pharmacological inhibitor of spermine oxidase (SMOX), is protective against neurodegeneration and inflammation in the models of diabetic retinopathy and excitotoxicity. In the present study, utilizing the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined the impact of SMOX blockade on retinal neurodegeneration and optic nerve inflammation. The increased expression of SMOX observed in EAE retinas was associated with a significant loss of retinal ganglion cells, degeneration of synaptic contacts, and reduced visual acuity. MDL 72527-treated mice exhibited markedly reduced motor deficits, improved neuronal survival, the preservation of synapses, and improved visual acuity compared to the vehicle-treated group. The EAE-induced increase in macrophage\/microglia was markedly reduced by SMOX inhibition. Upregulated acrolein conjugates in the EAE retina were decreased through MDL 72527 treatment. Mechanistically, the EAE-induced ERK-STAT3 signaling was blunted by SMOX inhibition. In conclusion, our studies demonstrate the potential benefits of targeting SMOX to treat MS-mediated neuroinflammation and vision loss.<\/jats:p>","DOI":"10.3390\/cells11244100","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T07:27:30Z","timestamp":1671434850000},"page":"4100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Treatment with MDL 72527 Ameliorated Clinical Symptoms, Retinal Ganglion Cell Loss, Optic Nerve Inflammation, and Improved Visual Acuity in an Experimental Model of Multiple Sclerosis"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5129-5318","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"},{"name":"Vascular Biology Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7207-7555","authenticated-orcid":false,"given":"Moaddey","family":"Alfarhan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"},{"name":"Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanna","family":"Baker","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Shenoy","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yini","family":"Liao","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry O.","family":"Henry-Ojo","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0230","authenticated-orcid":false,"given":"Payaningal R.","family":"Somanath","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"},{"name":"Vascular Biology Center, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-622X","authenticated-orcid":false,"given":"S. Priya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA"},{"name":"Charlie Norwood VA Medical Center, Augusta, GA 30904, USA"},{"name":"Vascular Biology Center, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia"},{"name":"Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. 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