ACTRIMS 2024 | Synaptic loss in the retina as a predictor of progression in MS

Synaptic involvement in multiple sclerosis (MS) has been overlooked compared to gray matter atrophy. Christian Cordano, MD, PhD, UCSF Weill Institute for Neurosciences, San Francisco, CA, has been investigating the impact of synaptic loss in MS and the mechanisms that drive it. The retina, due to its smaller and less complex nature compared to the brain, serves as a valuable area for studying synapses. Using experimental autoimmune encephalomyelitis (EAE) mouse models, researchers collected retinas and focused on the inner plexiform layer (IPL), which houses synapses. Quantification revealed a loss of functional synapses prior to the onset of symptoms, with this loss increasing over time and correlating with disease progression. Investigating patients transitioning from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS), researchers noted a substantial loss of IPL in those progressing to SPMS compared to those remaining in RRMS. Notably, proteomic analyses revealed an important correlation between synaptic loss and MOG, even after adjusting for NfL, suggesting that demyelination induces synaptic loss independent of its effect on axons. Dr Cordano comments on ongoing projects to better understand the mechanisms involved in this process and the promise of IPL metrics as predictive markers. This interview took place during the annual ACTRIMS Forum 2024.

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