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Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis.
Cordano, Christian; Werneburg, Sebastian; Abdelhak, Ahmed; Bennett, Daniel J; Beaudry-Richard, Alexandra; Duncan, Greg J; Oertel, Frederike C; Boscardin, W John; Yiu, Hao H; Jabassini, Nora; Merritt, Lauren; Nocera, Sonia; Sin, Jung H; Samana, Isaac P; Condor Montes, Shivany Y; Ananth, Kirtana; Bischof, Antje; Nourbakhsh, Bardia; Hauser, Stephen L; Cree, Bruce A C; Emery, Ben; Schafer, Dorothy P; Chan, Jonah R; Green, Ari J.
Afiliação
  • Cordano C; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San M
  • Werneburg S; Department of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA; Department of Ophthalmology & Visual Sciences, Michigan Neuroscience Institute, University of Michigan - Michigan Medicine, Ann Arbor, MI, USA.
  • Abdelhak A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Bennett DJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Beaudry-Richard A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Duncan GJ; Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Oertel FC; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Boscardin WJ; Department of Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
  • Yiu HH; Department of Biology, University of Maryland, College Park, MD, USA.
  • Jabassini N; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Merritt L; Department of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Nocera S; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Sin JH; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Samana IP; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Condor Montes SY; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Ananth K; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Bischof A; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Nourbakhsh B; Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
  • Hauser SL; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Cree BAC; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Emery B; Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
  • Schafer DP; Department of Neurobiology, Brudnik Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Chan JR; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jonah.chan@ucsf.edu.
  • Green AJ; UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: agreen@ucsf.edu.
Cell Rep Med ; 5(4): 101490, 2024 Apr 16.
Article em En | MEDLINE | ID: mdl-38574736
ABSTRACT
While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article