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| Item Type: | Article |
|---|---|
| Title: | Synaptic injury in the inner plexiform layer of the retina is associated with progression in multiple sclerosis |
| Creators Name: | Cordano, C., Werneburg, S., Abdelhak, A., Bennett, D.J., Beaudry-Richard, A., Duncan, G.J., Oertel, F.C., Boscardin, W.J., Yiu, H.H., Jabassini, N., Merritt, L., Nocera, S., Sin, J.H., Samana, I.P., Condor Montes, S.Y., Ananth, K., Bischof, A., Nourbakhsh, B., Hauser, S.L., Cree, B.A.C., Emery, B., Schafer, D.P., Chan, J.R. and Green, A.J. |
| 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. |
| Keywords: | Optical Coherence Tomography, Retina, Synaptic Injury, Experimental Autoimmune Encephalomyelitis, EAE, Demyelination, Serum Proteomics, Blood Biomarkers, Animals |
| Source: | Cell Reports Medicine |
| ISSN: | 2666-3791 |
| Publisher: | Elsevier / Cell Press |
| Volume: | 5 |
| Number: | 4 |
| Page Range: | 101490 |
| Date: | 16 April 2024 |
| Official Publication: | https://doi.org/10.1016/j.xcrm.2024.101490 |
| PubMed: | View item in PubMed |
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