Multimodal Longitudinal Optical Imaging Reveals Optic Neuritis Preceding Retinal Pathology in Experimental Autoimmune Encephalomyelitis.

IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY
Raphael Raspe, Robert Günther, Ralf Uecker, Asylkhan Rakhymzhan, Friedemann Paul, Helena Radbruch, Raluca Aura Niesner, Anja Erika Hauser
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引用次数: 0

Abstract

Background and objectives: Inflammatory demyelinating diseases of the CNS, chief among them multiple sclerosis (MS), are a major cause of disability in young adults. Early manifestations of MS commonly involve visual dysfunction, which is often caused by optic neuritis and is accompanied by quantifiable structural changes of the anterior visual pathway. Retinal optical coherence tomography (OCT) has emerged as an important tool for clinical assessment of these structural alterations, but the underlying pathobiological mechanisms and temporal dynamics are yet poorly understood at a cellular level.

Methods: Using the experimental autoimmune encephalomyelitis (EAE) model of MS in fluorescent reporter mouse strains for neuronal function and innate immune cells, we use a unique combination of retinal intravital 2-photon microscopy (2PM) and OCT. In this fashion, we elucidate the spatiotemporal interplay of functional and structural retinal changes over the course of 1 month after EAE induction, with histopathologic imaging validating main results.

Results: While all mice display histologic signs of optic neuritis early after EAE induction and independently of motor symptom severity, retinal signs of neuronal stress and parenchymal immune activation spike well after clinical peak of disease, with no signs of lasting structural damage appearing within 1 month after EAE induction. Thus, local retinal endpoints appear to be functions of downstream axonal damage rather than of immediate immune activation directed at the retina. However, as early as 1 week after EAE induction, retinal 2PM can detect recruitment of perivascular immune cells towards the optic nerve (ON), providing the earliest sign of disease activity in otherwise clinically inconspicuous mice.

Discussion: Our work identifies the recruitment of CX3CR1+ cells to the ON as an early sign of disease underlining the importance of combined structural and functional retinal imaging for the spatiotemporal characterization of neuroinflammatory and neurodegenerative processes. It further proposes retinal phagocyte orientation, morphology, and abundance as potential surrogate markers for neurodegenerative activity.

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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
219
审稿时长
8 weeks
期刊介绍: Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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