Functional evolution of visual involvement in experimental autoimmune encephalomyelitis

Marenna, Silvia; Huang, Su‐Chun; Castoldi, Valerio; d’Isa, Raffaele; Costa, Gloria Dalla; Comı, Gıancarlo; Leocani, Letizia

doi:10.1177/2055217320963474

Cited by 10 publications

(19 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, MRI analysis in guinea pig EAE suggests that damage to the blood optic nerve barrier occurs early after disease induction, prior to clinical onset 33 . In the present study, XPCT of the optic nerve of EAE-affected mice enabled the clear visualization of a massive inflammatory lesion in the optic nerve, accompanied by nerve atrophy; such observations have only been made previously in EAE with 2D histology techniques 34,35 , with some evidence of inflammation and demyelination already at 7 dpi 36 . Analysis of optic nerve damage is most often performed in MS using optical coherence tomography.…”

Section: Discussionsupporting

confidence: 53%

Multilevel X-ray imaging approach to assess the sequential evolution of multi-organ damage in multiple sclerosis

et al. 2022

View full text Add to dashboard Cite

The 3D complexity of biological tissues and intricate structural-functional connections call for state-of-the-art X-ray imaging approaches to overcome limitations of classical imaging. Unlike other imaging techniques, X-ray phase-contrast tomography (XPCT) offers a highly sensitive 3D imaging approach to investigate different disease-relevant networks at levels ranging from single cell through to intact organ. We present here a concomitant study of the evolution of tissue damage and inflammation in different organs affected by the disease in the murine model for multiple sclerosis, a demyelinating autoimmune disorder of the central nervous system. XPCT identifies and monitors structural and cellular alterations throughout the central nervous system, but also in the gut, and eye, of mice induced to develop multiple sclerosis-like disease and sacrificed at pre-symptomatic and symptomatic time points. This study details the sequential evolution of multi-organ damages in the murine multiple sclerosis model showing the disease development and progression which is of relevance for the human case.

show abstract

Section: Discussionsupporting

confidence: 53%

Multilevel X-ray imaging approach to assess the sequential evolution of multi-organ damage in multiple sclerosis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Body temperature was maintained with a homeothermic blanket system at 36.5 ± 0.5 °C. pERG was recorded from one eye at a time using a corneal electrode connected via flexible cables to a Micromed amplifier, as reported previously ( Marenna et al, 2020 ). Each session included 3 trains of 10 flash stimuli (with 130 mJ intensity, 10ms duration and 0.5 Hz frequency) delivered with a flash photostimulator (Micromed, Mogliano Veneto, Italy) placed at 15 cm from the stimulated eye.…”

Section: Methodsmentioning

confidence: 99%

MCT1-dependent energetic failure and neuroinflammation underlie optic nerve degeneration in Wolfram syndrome mice

Rossi

Ordazzo

Vanni

et al. 2023

eLife

Self Cite

View full text Add to dashboard Cite

Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in the WFS1 gene leading to a wide spectrum of clinical dysfunctions, among which blindness, diabetes and neurological deficits are the most prominent. WFS1 encodes for the endoplasmic reticulum (ER) resident transmembrane protein wolframin with multiple functions in ER processes. However, the WFS1-dependent etiopathology in retinal cells is unknown. Herein, we showed that Wfs1 mutant mice developed early retinal electrophysiological impairments followed by marked visual loss. Interestingly, axons and myelin disruption in the optic nerve preceded the degeneration of the retinal ganglion cell bodies in the retina. Transcriptomics at pre-degenerative stage revealed the STAT3-dependent activation of proinflammatory glial markers with reduction of the homeostatic and pro-survival factors glutamine synthetase and BDNF. Furthermore, label-free comparative proteomics identified a significant reduction of the monocarboxylate transport isoform 1 (MCT1) and its partner basigin that are highly enriched on retinal glia and myelin-forming oligodendrocytes in optic nerve together with wolframin. Loss of MCT1 caused a failure in lactate transfer from glial to neuronal cell bodies and axons leading to a chronic hypometabolic state. Thus, this bioenergetic impairment is occurring concurrently both within the axonal regions and cell bodies of the retinal ganglion cells, selectively endangering their survival while impacting less on other retinal cells. This metabolic dysfunction occurs months before the frank RGC degeneration suggesting an extended time-window for intervening with new therapeutic strategies focused on boosting retinal and optic nerve bioenergetics in WS1.

show abstract

“…However, the spatio-temporal relationship of demyelination, axonal loss, and neurodegeneration in the spino- and retino-thalamic pathways and how these pathological changes translate to structural and functional visual deficits is not clear. Timing delays in the visual evoked potential (VEP) are a well-established feature of both MS [ 28 – 30 ] and EAE [ 27 , 31 , 32 ]. In the EAE model, we show that VEP delays coincided with acute loss of myelinated axons in the optic nerve and SC white matter while OCT imaging tracked retinal thinning consistent with loss of RGCs and SC ventral horn neurons during chronic EAE.…”

mentioning

confidence: 99%

Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis

Mey

Evonuk

Chappell

et al. 2022

acta neuropathol commun

View full text Add to dashboard Cite

Thalamic volume is associated with clinical disability in multiple sclerosis (MS) and is vulnerable to secondary neurodegeneration due to its extensive connectivity throughout the central nervous system (CNS). Using a model of autoimmune demyelination that exhibits CNS-infiltrating immune cells in both spinal cord white matter and optic nerve, we sought to evaluate neurodegenerative changes due to lesions affecting the spino- and retino-thalamic pathways. We found comparable axonal loss in spinal cord white matter and optic nerve during the acute phase of disease consistent with synaptic loss, but not neuronal cell body loss in the thalamic nuclei that receive input from these discrete pathways. Loss of spinal cord neurons or retinal ganglion cells retrograde to their respective axons was not observed until the chronic phase of disease, where optical coherence tomography (OCT) documented reduced inner retinal thickness. In patients with relapsing–remitting MS without a history of optic neuritis, OCT measures of inner retinal volume correlated with retino-thalamic (lateral geniculate nucleus) and spino-thalamic (ventral posterior nucleus) volume as well as neuroperformance measures. These data suggest retinal imaging may serve as an important noninvasive predictor of neurodegeneration in MS.

show abstract

Functional evolution of visual involvement in experimental autoimmune encephalomyelitis

Cited by 10 publications

References 34 publications

Multilevel X-ray imaging approach to assess the sequential evolution of multi-organ damage in multiple sclerosis

Multilevel X-ray imaging approach to assess the sequential evolution of multi-organ damage in multiple sclerosis

MCT1-dependent energetic failure and neuroinflammation underlie optic nerve degeneration in Wolfram syndrome mice

Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis

Contact Info

Product

Resources

About