In Vivo Molecular Changes in the Retina of Patients With Multiple Sclerosis

Alba-Arbalat, Salut; Andorrà, Magí; Sánchez-Dalmau, Bernardo; Camós-Carreras, Anna; Dotti-Boada, Marina; Pulido-Valdeolivas, Irene; Llufriú, Sara; Blanco, Yolanda; Sepúlveda, María; Sáiz, Albert; Batet, Oscar; Bilbao, Iker; Torre, Iratxe; Amat-Roldán, Ivan; Martínez-Lapiscina, Elena H.; Villoslada, Pablo

doi:10.1167/iovs.62.6.11

Cited by 15 publications

(13 citation statements)

References 49 publications

(57 reference statements)

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“…These observations are in keeping with our previous work which demonstrated no motor impairment after in vivo Raman recordings and resolution of mild T2 signal changes on 7T MRI by 2‐wk post‐procedure 5 . Multiple groups have performed in vivo Raman measurements on a variety of tissues with no evidence of significant tissue injury, highlighting the potential of Raman spectroscopy as a safe technique for tissue analysis 37–42 …”

Section: Discussionsupporting

confidence: 87%

“…5 Multiple groups have performed in vivo Raman measurements on a variety of tissues with no evidence of significant tissue injury, highlighting the potential of Raman spectroscopy as a safe technique for tissue analysis. [37][38][39][40][41][42] In conclusion, we present the technique of optical EMG, a novel combination of electrophysiology and Raman spectroscopy. As proof of concept, we demonstrate that optical EMG can provide sensitive, quantitative measures of disease using the SOD1 G93A model of ALS.…”

Section: Resultsmentioning

confidence: 99%

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Combining electromyography and Raman spectroscopy: optical EMG

et al. 2023

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Introduction/AimsElectromyography (EMG) remains a key component of the diagnostic work‐up for suspected neuromuscular disease, but it does not provide insight into the molecular composition of muscle which can provide diagnostic information. Raman spectroscopy is an emerging neuromuscular biomarker capable of generating highly specific, molecular fingerprints of tissue. Here, we present “optical EMG,” a combination of EMG and Raman spectroscopy, achieved using a single needle.MethodsAn optical EMG needle was created to collect electrophysiological and Raman spectroscopic data during a single insertion. We tested functionality with in vivo recordings in the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), using both transgenic (n = 10) and non‐transgenic (NTg, n = 7) mice. Under anesthesia, compound muscle action potentials (CMAPs), spontaneous EMG activity and Raman spectra were recorded from both gastrocnemius muscles with the optical EMG needle. Standard concentric EMG needle recordings were also undertaken. Electrophysiological data were analyzed with standard univariate statistics, Raman data with both univariate and multivariate analyses.ResultsA significant difference in CMAP amplitude was observed between SOD1G93A and NTg mice with optical EMG and standard concentric needles (p = .015 and p = .011, respectively). Spontaneous EMG activity (positive sharp waves) was detected in transgenic SOD1G93A mice only. Raman spectra demonstrated peaks associated with key muscle components. Significant differences in molecular composition between SOD1G93A and NTg muscle were identified through the Raman spectra.DiscussionOptical EMG can provide standard electrophysiological data and molecular Raman data during a single needle insertion and represents a potential biomarker for neuromuscular disease.

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Combining electromyography and Raman spectroscopy: optical EMG

et al. 2023

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“…Conversely, an increased expression of glutamate transporters has been described in other conditions such as optic neuritis [ 161 ], where glutamate excitotoxicity is linked to neuroinflammation. This may represent a compensatory mechanism occurring also in other brain areas in multiple sclerosis [ 162 , 163 ], though it may ultimately fail since increased retinal glutamate levels have been reported in multiple sclerosis [ 164 ].…”

Section: Glutamate Excitotoxicity In the Retinamentioning

confidence: 99%

Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration

Boccuni

Fairless

2022

Life

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Glutamate neurotransmission and metabolism are finely modulated by the retinal network, where the efficient processing of visual information is shaped by the differential distribution and composition of glutamate receptors and transporters. However, disturbances in glutamate homeostasis can result in glutamate excitotoxicity, a major initiating factor of common neurodegenerative diseases. Within the retina, glutamate excitotoxicity can impair visual transmission by initiating degeneration of neuronal populations, including retinal ganglion cells (RGCs). The vulnerability of RGCs is observed not just as a result of retinal diseases but has also been ascribed to other common neurodegenerative and peripheral diseases. In this review, we describe the vulnerability of RGCs to glutamate excitotoxicity and the contribution of different glutamate receptors and transporters to this. In particular, we focus on the N-methyl-d-aspartate (NMDA) receptor as the major effector of glutamate-induced mechanisms of neurodegeneration, including impairment of calcium homeostasis, changes in gene expression and signalling, and mitochondrial dysfunction, as well as the role of endoplasmic reticular stress. Due to recent developments in the search for modulators of NMDA receptor signalling, novel neuroprotective strategies may be on the horizon.

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“…Reactive oxygen species are critically involved in neurodegeneration 221 , particularly during an acute immune attack targeting the myelin sheath 222 , and the co-factors NADPH and NADH are pivotal for neuronal redox homeostasis. A recent analysis showed decreased NADH levels within the retinas of patients with MS 223 and an altered NAD + /NADH ratio in the serum of patients with MS, indicating chronic oxidative stress 224 . However, it remains to be determined whether this is a product of a defective defence mechanism or increased production of reactive oxygen species.…”

Section: Is Multiple Sclerosis a Metabolic Disease?mentioning

confidence: 99%

Thinking outside the box: non-canonical targets in multiple sclerosis

Bierhansl

Hartung

Aktaş

et al. 2022

Nat Rev Drug Discov

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Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system that causes demyelination, axonal degeneration and astrogliosis, resulting in progressive neurological disability. Fuelled by an evolving understanding of MS immunopathogenesis, the range of available immunotherapies for clinical use has expanded over the past two decades. However, MS remains an incurable disease and even targeted immunotherapies often fail to control insidious disease progression, indicating the need for new and exceptional therapeutic options beyond the established immunological landscape. In this Review, we highlight such non-canonical targets in preclinical MS research with a focus on five highly promising areas: oligodendrocytes; the blood–brain barrier; metabolites and cellular metabolism; the coagulation system; and tolerance induction. Recent findings in these areas may guide the field towards novel targets for future therapeutic approaches in MS.

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In Vivo Molecular Changes in the Retina of Patients With Multiple Sclerosis

Abstract: al. In vivo molecular changes in the retina of patients with multiple sclerosis.

Cited by 15 publications

References 49 publications

Combining electromyography and Raman spectroscopy: optical EMG

Combining electromyography and Raman spectroscopy: optical EMG

Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration

Thinking outside the box: non-canonical targets in multiple sclerosis

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