Early auto‐immune targeting of photoreceptor ribbon synapses in mouse models of multiple sclerosis

Autor: Mayur Dembla, Ajay Kesharwani, Sivaraman Natarajan, Claudia Fecher‐Trost, Richard Fairless, Sarah K Williams, Veit Flockerzi, Ricarda Diem, Karin Schwarz, Frank Schmitz
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 10, Iss 11, Pp 1-22 (2018)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201808926
Popis: Abstract Optic neuritis is one of the first manifestations of multiple sclerosis. Its pathogenesis is incompletely understood, but considered to be initiated by an auto‐immune response directed against myelin sheaths of the optic nerve. Here, we demonstrate in two frequently used and well‐validated mouse models of optic neuritis that ribbon synapses in the myelin‐free retina are targeted by an auto‐reactive immune system even before alterations in the optic nerve have developed. The auto‐immune response is directed against two adhesion proteins (CASPR1/CNTN1) that are present both in the paranodal region of myelinated nerves as well as at retinal ribbon synapses. This occurs in parallel with altered synaptic vesicle cycling in retinal ribbon synapses and altered visual behavior before the onset of optic nerve demyelination. These findings indicate that early synaptic dysfunctions in the retina contribute to the pathology of optic neuritis in multiple sclerosis.
Databáze: Directory of Open Access Journals
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