{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:37Z","timestamp":1787026837177,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>\n                    While great advances have been made in the immunomodulatory treatment of multiple sclerosis (MS), there is still an unmet need for drugs with neuroprotective potential. Dimethyl fumarate (DMF) has been suggested to exert both immunomodulatory and neuroprotective effects in MS. To investigate if DMF has neuroprotective effects independent of immunomodulation we evaluated its effects in the non-inflammatory animal models of light-induced photoreceptor loss and optic nerve crush. This might also reveal applications for DMF besides MS, such as age related macular degeneration. Retinal neurodegeneration was longitudinally assessed by\n                    <jats:italic>in vivo<\/jats:italic>\n                    retinal imaging using optical coherence tomography (OCT), and glutathione (GSH) measurements as well as histological investigations were performed to clarify the mode of action. For light-induced photoreceptor loss, one eye of C57BL\/6J mice was irradiated with a LED cold light lamp while for optic nerve crush the optic nerve was clamped behind the eye bulb. The other eye served as control. GSH was measured in the optic nerve, choroid and retina and immunohistological staining of retinal microglia (Iba1) was performed. Mice were treated with 15 or 30 mg DMF\/kg bodyweight or vehicle. While no protective effects were observed in optic nerve crush, in the light-induced retinal degeneration model DMF treatment significantly reduced retinal degeneration. In these mice, GSH levels in the retina and surrounding choroid were increased and histological investigations revealed less microglial activation in the outer retinal layers, suggesting both antioxidant and anti-inflammatory effects.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2020.601628","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T02:45:50Z","timestamp":1610592350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Neuroprotective Properties of Dimethyl Fumarate Measured by Optical Coherence Tomography in Non-inflammatory Animal Models"],"prefix":"10.3389","volume":"11","author":[{"given":"Michael","family":"Dietrich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad","family":"Nasiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sogol","family":"Samsam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Issberner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zippora","family":"Kohne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Albrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1136\/jim-2016-000339","article-title":"Update on disease-modifying therapies for multiple sclerosis","volume":"65","author":"Vargas","year":"2017","journal-title":"J Investig Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1002\/med.21567","article-title":"Dimethyl fumarate, a two-edged drug: current status and future directions","volume":"39","author":"Saidu","year":"2019","journal-title":"Med Res Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/S0140-6736(08)61619-0","article-title":"Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study","volume":"372","author":"Kappos","year":"2008","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1111\/j.1468-1331.2006.01292.x","article-title":"Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study","volume":"13","author":"Schimrigk","year":"2006","journal-title":"Eur J Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1056\/NEJMoa1114287","article-title":"Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis","volume":"367","author":"Gold","year":"2012","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","article-title":"Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis","volume":"367","author":"Fox","year":"2012","journal-title":"N Engl J Med"},{"key":"B7","first-page":"12","article-title":"Spotlight on fumarates","volume":"15","author":"Lee","year":"2008","journal-title":"Int MS J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/1742-2094-9-163","article-title":"Effects of dimethyl fumarate on neuroprotection and immunomodulation","volume":"9","author":"Albrecht","year":"2012","journal-title":"J Neuroinflammation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1093\/brain\/awq386","article-title":"Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway","volume":"134","author":"Linker","year":"2011","journal-title":"Brain"},{"key":"B10","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1124\/jpet.111.190132","article-title":"Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway","volume":"341","author":"Scannevin","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e183","DOI":"10.1212\/NXI.0000000000000183","article-title":"Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis","volume":"3","author":"Gross","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1093\/brain\/awaa062","article-title":"Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis","volume":"143","author":"Dietrich","year":"2020","journal-title":"Brain"},{"key":"B13","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1097\/WCO.0000000000000675","article-title":"Assessing the anterior visual pathway in optic neuritis: Recent experimental and clinical aspects","volume":"32","author":"Dietrich","year":"2019","journal-title":"Curr Opin Neurol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1007\/s00415-007-0538-3","article-title":"Optical coherence tomography measures axonal loss in multiple sclerosis independently of optic neuritis","volume":"254","author":"Albrecht","year":"2007","journal-title":"J Neurol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e000008","DOI":"10.1136\/bmjophth-2016-000008","article-title":"Whole-body positional manipulators for ocular imaging of anaesthetised mice and rats: a do-it-yourself guide","volume":"1","author":"Dietrich","year":"2017","journal-title":"BMJ Open Ophthalmol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12974-018-1111-y","article-title":"Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model","volume":"15","author":"Dietrich","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12974-019-1583-4","article-title":"Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis","volume":"16","author":"Cruz-Herranz","year":"2019","journal-title":"J Neuroinflammation"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.1212\/WNL.0000000000002774","article-title":"The APOSTEL recommendations for reporting quantitative optical coherence tomography studies","volume":"86","author":"Cruz-Herranz","year":"2016","journal-title":"Neurology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e58571","DOI":"10.3791\/58571","article-title":"Using optical coherence tomography and optokinetic response as structural and functional visual system readouts in mice and rats","volume":"143","author":"Dietrich","year":"2019","journal-title":"J Vis Exp"},{"key":"B20","doi-asserted-by":"publisher","first-page":"577163","DOI":"10.1016\/j.jneuroim.2020.577163","article-title":"Enhanced cognitive performance in experimental autoimmune encephalomyelitis mice treated with dimethyl fumarate after the appearance of disease symptoms","volume":"340","author":"das Neves","year":"2020","journal-title":"J Neuroimmunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4777","DOI":"10.1073\/pnas.1603907113","article-title":"Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2","volume":"113","author":"Schulze-Topphoff","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6093903","DOI":"10.1155\/2017\/6093903","article-title":"Dimethyl fumarate induces glutathione recycling by upregulation of glutathione reductase","volume":"2017","author":"Hoffmann","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.neuron.2012.06.018","article-title":"Mechanisms of age-related macular degeneration","volume":"75","author":"Ambati","year":"2012","journal-title":"Neuron"},{"key":"B24","doi-asserted-by":"publisher","first-page":"844","DOI":"10.3389\/fphar.2020.00844","article-title":"Eye-light on age-related macular degeneration: targeting Nrf2-pathway as a novel therapeutic strategy for retinal pigment epithelium","volume":"11","author":"Catanzaro","year":"2020","journal-title":"Front Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1080\/09273948.2017.1305727","article-title":"Sympathetic ophthalmia","volume":"25","author":"Cunningham","year":"2017","journal-title":"Ocul Immunol Inflamm"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.1167\/iovs.10-6311","article-title":"Optic nerve crush mice followed longitudinally with spectral domain optical coherence tomography","volume":"52","author":"Gabriele","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.1167\/iovs.08-2764","article-title":"In vivo quantitative evaluation of the rat retinal nerve fiber layer with optical coherence tomography","volume":"50","author":"Nagata","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1167\/iovs.17-23148","article-title":"Response of the retinal nerve fiber layer reflectance and thickness to optic nerve crush","volume":"59","author":"Huang","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e40352","DOI":"10.1371\/journal.pone.0040352","article-title":"Longitudinal in vivo imaging of retinal ganglion cells and retinal thickness changes following optic nerve injury in mice","volume":"7","author":"Chauhan","year":"2012","journal-title":"PLoS ONE"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1167\/iovs.18-26441","article-title":"Optical coherence tomography angiography in mice: quantitative analysis after experimental models of retinal damage","volume":"60","author":"Smith","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1167\/iovs.19-26560","article-title":"A mixture of U.S. food and drug administration-approved monoaminergic drugs protects the retina from light damage in diverse models of night blindness","volume":"60","author":"Leinonen","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1167\/iovs.18-24398","article-title":"Monomethyl fumarate protects the retina from light-induced retinopathy","volume":"60","author":"Jiang","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.exer.2016.12.001","article-title":"Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light","volume":"154","author":"Chen","year":"2017","journal-title":"Exp Eye Res"},{"key":"B34","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00401-015-1452-x","article-title":"Cell type-specific Nrf2 expression in multiple sclerosis lesions","volume":"130","author":"Licht-Mayer","year":"2015","journal-title":"Acta Neuropathol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s00401-015-1422-3","article-title":"Fumarates modulate microglia activation through a novel HCAR2 signaling pathway and rescue synaptic dysregulation in inflamed CNS","volume":"130","author":"Parodi","year":"2015","journal-title":"Acta Neuropathol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.601628\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T04:16:49Z","timestamp":1611116209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2020.601628\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":35,"alternative-id":["10.3389\/fneur.2020.601628"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2020.601628","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]},"article-number":"601628"}}