Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.

Background And Objectives: Despite the absence of acute lesion activity in multiple sclerosis (MS), chronic neurodegeneration continues to progress, and a potential underlying mechanism could be the kynurenine pathway (KP). Prolonged activation of the KP from chronic inflammation is known to exacerbate the progression of neurodegenerative diseases through the production of neurotoxic metabolites. Among the 8 KP metabolites, six of them, namely kynurenine (KYN), 3-hydroxylkynurenine (3HK), anthranilic acid (AA), kynurenic acid (KYNA), and quinolinic acid (QUIN), have been associated with neurodegeneration.

VEP Latency Delay Reflects Demyelination Beyond the Optic Nerve in the Cuprizone Model.

Purpose: Remyelination therapies are advancing for multiple sclerosis, focusing on visual pathways and using visual evoked potentials (VEPs) for de/remyelination processes. While the cuprizone (CZ) model and VEPs are core tools in preclinical trials, many overlook the posterior visual pathway. This study aimed to assess functional and structural changes across the murine visual pathway during de/remyelination.

Mechanisms of Transsynaptic Degeneration in the Aging Brain.

A prominent feature in many neurodegenerative diseases involves the spread of the pathology from the initial site of damage to anatomically and functionally connected regions of the central nervous system (CNS), referred to as transsynaptic degeneration (TSD). This review covers the possible mechanisms of both retrograde and anterograde TSD in various age-related neurodegenerative diseases, including synaptically and glial mediated changes contributing to TDS and their potential as therapeutic targets. This phenomenon is well documented in clinical and experimental studies spanning various neurodegenerative diseases and their respective models, with a significant emphasis on the visual pathway, to be explored herein.

RXR agonist, 9-cis-13,14-dihydroretinoic acid (9CDHRA), reduces damage and protects from demyelination in transsynaptic degeneration model.

Neurodegenerative and demyelinating disease, such as multiple sclerosis (MS) are at the forefront of medical research and the discovery of new drugs and therapeutics. One phenomenon of degeneration seen in these diseases is transsynaptic degeneration (TSD), where damage from one axon spreads to the other axons that are connected to it synaptically. It has previously been found that demyelination occurs prior to neuronal loss in an experimental form of induced TSD.

POSTINTRAVITREAL INJECTION AND POSTCATARACT EXTRACTION ENDOPHTHALMITIS VISUAL OUTCOMES BY ORGANISM: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Purpose: To compare visual outcomes of endophthalmitis following intravitreal injections (IVIs) and cataract extraction by causative organism.

Methods: Searches in Cochrane Central Register of Controlled Trials, MEDLINE, and Embase identified articles reporting visual outcomes by causative organisms in post-IVI and cataract extraction endophthalmitis cases from January 2010 to February 2022. A random-effects meta-analysis compared visual improvement among endophthalmitis cases caused by causative organisms.

Glial Cell Activation and Immune Responses in Glaucoma: A Systematic Review of Human Postmortem Studies of the Retina and Optic Nerve.

Although researched extensively the understanding regarding mechanisms underlying glaucoma pathogenesis remains limited. Further, the exact mechanism behind neuronal death remains elusive. The role of neuroinflammation in retinal ganglion cell (RGC) death has been prominently theorised.

The role of myelin in neurodegeneration: implications for drug targets and neuroprotection strategies.

Myelination of axons in the central nervous system offers numerous advantages, including decreased energy expenditure for signal transmission and enhanced signal speed. The myelin sheaths surrounding an axon consist of a multi-layered membrane that is formed by oligodendrocytes, while specific glycoproteins and lipids play various roles in this formation process. As beneficial as myelin can be, its dysregulation and degeneration can prove detrimental.

Amyloid-beta and tau protein beyond Alzheimer's disease.

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades.

Anti-inflammatory Effects of Siponimod in a Mouse Model of Excitotoxicity-Induced Retinal Injury.

Glaucoma is a leading cause of permanent blindness worldwide and is characterized by neurodegeneration linked to progressive retinal ganglion cell (RGC) death, axonal damage, and neuroinflammation. Glutamate excitotoxicity mediated through N-methyl-D-aspartate (NMDA) receptors plays a crucial role in glaucomatous RGC loss. Sphingosine 1-phosphate receptors (S1PRs) are important mediators of neurodegeneration and neuroinflammation in the brain and the retina.

Retinal thickness and vascular parameters using optical coherence tomography in Alzheimer's disease: a meta-analysis.

Examining the retinal tissue has the potential to provide a unique method and technique to quantify Alzheimer's disease-related changes in participants at various stages of the disease. In this meta-analysis, we aimed to investigate the association of various optical coherence tomography parameters with Alzheimer's disease and whether retinal measurements can be used to differentiate between Alzheimer's disease and control subjects. Scientific databases including Google Scholar, Web of Science, and PubMed were systematically searched for published articles that evaluated retinal nerve fiber layer thickness and retinal microvascular network in Alzheimer's disease and control subjects.

Oxidative Stress Induced Dysfunction of Protein Synthesis in 661W Mice Photoreceptor Cells.

Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood.

Combined versus Sequential Pars Plana Vitrectomy and Phacoemulsification for Macular Hole and Epiretinal Membrane: A Systematic Review and Meta-Analysis.

Topic: Comparing the efficacy and safety between combined and sequential pars plana vitrectomy and phacoemulsification for macular hole (MH) and epiretinal membrane (ERM).

Clinical Relevance: The standard of care for MH and ERM is vitrectomy, which increases the risk of developing cataract. Combined phacovitrectomy eliminates the need for a second surgery.

Evaluating associations of RNFL thickness and multifocal VEP with cognitive assessment and brain MRI volumes in older adults: Optic nerve decline and cognitive change (ONDCC) initiative.

To examine the relationships of retinal structural (optical coherence tomography) and visual functional (multifocal visual evoked potentials, mfVEP) indices with neuropsychological and brain structural measurements in healthy older subjects. 95 participants (mean (SD) age 68.1 (9.

S1PR1 signaling attenuates apoptosis of retinal ganglion cells via modulation of cJun/Bim cascade and Bad phosphorylation in a mouse model of glaucoma.

Glaucoma is a complex neurodegenerative disease characterized by optic nerve damage and apoptotic retinal ganglion cell (RGC) death, and is the leading cause of irreversible blindness worldwide. Among the sphingosine 1-phosphate receptors (S1PRs) family, S1PR1 is a highly expressed subtype in the central nervous system and has gained rapid attention as an important mediator of pathophysiological processes in the brain and the retina. Our recent study showed that mice treated orally with siponimod drug exerted neuroprotection via modulation of neuronal S1PR1 in experimental glaucoma.

Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.

Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling-based quantitative mass-spectrometric approach to investigate the mechanism of action of Fingolimod.

Neuroserpin, a crucial regulator for axogenesis, synaptic modelling and cell-cell interactions in the pathophysiology of neurological disease.

Neuroserpin is an axonally secreted serpin that is involved in regulating plasminogen and its enzyme activators, such as tissue plasminogen activator (tPA). The protein has been increasingly shown to play key roles in neuronal development, plasticity, maturation and synaptic refinement. The proteinase inhibitor may function both independently and through tPA-dependent mechanisms.

Long-term Effect of Permanent Demyelination on Axonal Survival in Multiple Sclerosis.

Background And Objectives: To investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).

Methods: Only patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits.

TrkB Receptor Agonist 7,8 Dihydroxyflavone is Protective Against the Inner Retinal Deficits Induced by Experimental Glaucoma.

Glaucoma is an age-related neurodegenerative disorder characterized by retinal ganglion cell (RGC) degeneration and excavation of the optic nerve head (ONH). It is associated with an increase in intraocular pressure (IOP) and progressive decline in the visual field. Reduction in the retrograde axonal transport of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) from the brain to the neuronal cell bodies in retina, has been suggested as one of the key mechanisms underlying selective degeneration of ganglion cells and optic nerve in glaucoma.