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Progress in Retinal and Eye Research Jul 2023The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend... (Review)
Review
The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies located in the outer nuclear layer and radially project toward the outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial anatomy is highlighted in many macular disorders including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and en face optical coherence tomography (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow in vivo visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the "angular sign of HFL hyperreflectivity" (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.
Topics: Humans; Tomography, Optical Coherence; Cross-Sectional Studies; Retina; Retinal Diseases; Macular Degeneration
PubMed: 36333227
DOI: 10.1016/j.preteyeres.2022.101135 -
Brain : a Journal of Neurology Dec 2023Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing data from nearly 10 000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n = 6 from five families), AAGGC (n = 2 from one family) and AGAGG (n = 1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion. While AAAAG, AAAGGG and AAGAG expansions appear to be benign, we revealed a pathogenic role for large AAAGG repeat configuration expansions (n = 5). Long-read sequencing was used to characterize the entire repeat sequence, and six patients exhibited a pure AGGGC expansion, while the other patients presented complex motifs with AAGGG or AAAGG interruptions. All pathogenic motifs appeared to have arisen from a common haplotype and were predicted to form highly stable G quadruplexes, which have previously been demonstrated to affect gene transcription in other conditions. The assessment of these novel configurations is warranted in CANVAS patients with negative or inconclusive genetic testing. Particular attention should be paid to carriers of compound AAGGG/AAAGG expansions when the AAAGG motif is very large (>500 repeats) or the AAGGG motif is interrupted. Accurate sizing and full sequencing of the satellite repeat with long-read sequencing is recommended in clinically selected cases to enable accurate molecular diagnosis and counsel patients and their families.
Topics: Humans; Bilateral Vestibulopathy; Cerebellar Ataxia; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Syndrome; Vestibular Diseases
PubMed: 37450567
DOI: 10.1093/brain/awad240 -
Advanced Healthcare Materials Jul 2023Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell...
Treatment with Mesenchymal Stem Cell-Derived Nanovesicle-Containing Gelatin Methacryloyl Hydrogels Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization.
Osteoarthritis is a degenerative disorder that can severely affect joints, and new treatment strategies are urgently needed. Administration of mesenchymal stem cell (MSC)-derived exosomes is a promising therapeutic strategy in osteoarthritis treatment. However, the poor yield of exosomes is an obstacle to the use of this modality in the clinic. Herein, a promising strategy is developed to fabricate high-yield exosome-mimicking MSC-derived nanovesicles (MSC-NVs) with enhanced regenerative and anti-inflammatory capabilities. MSC-NVs are prepared using an extrusion approach and are found to increase chondrocyte and human bone marrow MSC differentiation, proliferation, and migration, in addition to inducing M2 macrophage polarization. Furthermore, gelatin methacryloyl (GelMA) hydrogels loaded with MSC-NVs (GelMA-NVs) are formulated, which exhibit sustained release of MSC-NVs and are shown to be biocompatible with excellent mechanical properties. In a mouse osteoarthritis model constructed by surgical destabilization of the medial meniscus (DMM), GelMA-NVs effectively ameliorate osteoarthritis severity, reduce the secretion of catabolic factors, and enhance matrix synthesis. Furthermore, GelMA-NVs induce M2 macrophage polarization and inflammatory response inhibition in vivo. The findings demonstrate that GelMA-NVs hold promise for osteoarthritis treatment through modulation of chondrogenesis and macrophage polarization.
Topics: Mice; Animals; Humans; Hydrogels; Chondrogenesis; Osteoarthritis; Gelatin; Disease Models, Animal; Macrophages; Mesenchymal Stem Cells
PubMed: 36848378
DOI: 10.1002/adhm.202300315 -
Cardiology Clinics Aug 2023Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be... (Review)
Review
Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.
Topics: Humans; Muscular Dystrophies; Arrhythmias, Cardiac; Heart Block; Myocardium; Myocarditis; Arthritis, Rheumatoid; Heart Diseases
PubMed: 37321693
DOI: 10.1016/j.ccl.2023.03.008 -
Turkish Journal of Ophthalmology Oct 2023Myopia, including pathologic myopia, has seen a significant increase in prevalence in recent years. It is a significant cause of irreversible vision loss worldwide and... (Review)
Review
Myopia, including pathologic myopia, has seen a significant increase in prevalence in recent years. It is a significant cause of irreversible vision loss worldwide and prediction models demonstrate the substantial future impact on the population. With increased awareness and research, it is possible to prevent blindness on a large scale in the younger, productive age group affected by myopic maculopathy (MM). The vision-threatening manifestations of pathologic myopia include myopic choroidal neovascularization, macular atrophy, maculoschisis, macular hole, and retinal detachment. Myopic traction maculopathy (MTM) is a progressive manifestation of pathologic myopia and its treatment includes pars plana vitrectomy, macular buckle, or a combination. In this article we aim to review the diagnosis, clinical characteristics, and treatment of MM with an emphasis on recent developments in the surgical management of MTM. We discuss commercially available macular buckles, along with potential advantages to the use of macular buckle in MM. We review the new MTM staging system and its role in determining surgical management of these complex cases.
Topics: Humans; Myopia, Degenerative; Visual Acuity; Tomography, Optical Coherence; Retinal Diseases; Macular Degeneration; Vision Disorders; Blindness
PubMed: 37870043
DOI: 10.4274/tjo.galenos.2023.59844 -
Journal of Inflammation Research 2023Degenerative diseases affect people's life and health and cause a severe social burden. Relevant mechanisms of microglia have been studied, aiming to control and reduce... (Review)
Review
Degenerative diseases affect people's life and health and cause a severe social burden. Relevant mechanisms of microglia have been studied, aiming to control and reduce degenerative disease occurrence effectively. This review discussed the specific mechanisms underlying microglia in neurodegenerative diseases, age-related hearing loss, Alzheimer's disease, Parkinson's disease, and peripheral nervous system (PNS) degenerative diseases. It also reviewed the studies of microglia inhibitors (PLX3397/PLX5622) and activators (lipopolysaccharide), and suggested that reducing microglia can effectively curb the genesis and progression of degenerative diseases. Finally, microglial cells' anti-inflammatory and pro-inflammatory dual role was considered the critical communication point in central and peripheral degenerative diseases. Although it is difficult to describe the complex morphological structure of microglia in a unified manner, this does not prevent them from being a target for future treatment of neurodegenerative diseases.
PubMed: 38107384
DOI: 10.2147/JIR.S440377 -
Trends in Neurosciences Jan 2024Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become... (Review)
Review
Oligodendrocytes (OLs), the myelin-generating cells of the central nervous system (CNS), are active players in shaping neuronal circuitry and function. It has become increasingly apparent that injury to cells within the OL lineage plays a central role in neurodegeneration. In this review, we focus primarily on three degenerative disorders in which white matter loss is well documented: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We discuss clinical data implicating white matter injury as a key feature of these disorders, as well as shared and divergent phenotypes between them. We examine the cellular and molecular mechanisms underlying the alterations to OLs, including chronic neuroinflammation, aggregation of proteins, lipid dysregulation, and organellar stress. Last, we highlight prospects for therapeutic intervention targeting the OL lineage to restore function.
Topics: Humans; Neurodegenerative Diseases; White Matter; Alzheimer Disease; Parkinson Disease; Amyotrophic Lateral Sclerosis
PubMed: 38052682
DOI: 10.1016/j.tins.2023.11.003 -
Clinical & Experimental Optometry Aug 2023Corneal cross-linking is a photopolymerization technique traditionally used to strengthen corneal tissue. Corneal cross-linking utilizes riboflavin (vitamin B2) as a... (Review)
Review
Corneal cross-linking is a photopolymerization technique traditionally used to strengthen corneal tissue. Corneal cross-linking utilizes riboflavin (vitamin B2) as a photosensitizer and ultraviolet-A light (UVA) to create strong covalent bonds within the corneal stroma, increasing tissue stiffness. Multiple studies have demonstrated corneal cross-linking's effectiveness in treating corneal ectasia, a progressive, degenerative, and non-inflammatory thinning disorder, as quantified by key tomographic, refractive, and visual parameters. Since its introduction two decades ago, corneal cross-linking has surpassed its original application in halting corneal ectatic disease and its application has expanded into several other areas. Corneal cross-linking also possesses antibacterial, antienzymolytic and antioedematous properties, and has since become a tool in treating microbial keratitis, correcting refractive error, preventing iatrogenic ectasia, stabilising bullous keratopathy and controlling post keratoplasty ametropia. This review provides an overview of the current evidence base for the therapeutic non-ectasia applications of cornea cross-linking and looks at future developments in the field.
Topics: Humans; Dilatation, Pathologic; Cross-Linking Reagents; Collagen; Cornea; Photosensitizing Agents; Riboflavin; Photochemotherapy; Corneal Diseases; Ultraviolet Rays; Refractive Errors; Keratoconus
PubMed: 36690333
DOI: 10.1080/08164622.2022.2159790