Cordano, ChristianWerneburg, SebastianAbdelhak, AhmedBennett, Daniel JBeaudry-Richard, AlexandraDuncan, Greg JOertel, Frederike CBoscardin, W JohnYiu, Hao HJabassini, NoraMerritt, LaurenNocera, SoniaSin, Jung HSamana, Isaac PCondor Montes, Shivany YAnanth, KirtanaBischof, AntjeNourbakhsh, BardiaHauser, Stephen LCree, Bruce A CEmery, BenSchafer, Dorothy PChan, Jonah RGreen, Ari J2024-05-232024-05-232024-04-03Cordano C, Werneburg S, Abdelhak A, Bennett DJ, Beaudry-Richard A, Duncan GJ, Oertel FC, Boscardin WJ, Yiu HH, Jabassini N, Merritt L, Nocera S, Sin JH, Samana IP, Condor Montes SY, Ananth K, Bischof A; UCSF MS EPIC Team; Nourbakhsh B, Hauser SL, Cree BAC, Emery B, Schafer DP, Chan JR, Green AJ. Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis. Cell Rep Med. 2024 Apr 16;5(4):101490. doi: 10.1016/j.xcrm.2024.101490. Epub 2024 Apr 3. PMID: 38574736; PMCID: PMC11031420.2666-379110.1016/j.xcrm.2024.10149038574736https://hdl.handle.net/20.500.14038/53360While 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.enCopyright 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/EAEblood biomarkersdemyelinationexperimental autoimmune encephalomyelitisoptical coherence tomographyretinaserum proteomicssynaptic injuryJournal ArticleCell reports. Medicine