scholarly journals The retinal toxicity profile towards assemblies of Amyloid-β indicate the predominant pathophysiological activity of oligomeric species

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Efrat Naaman ◽  
Sarah Ya’ari ◽  
Chen Itzkovich ◽  
Shadi Safuri ◽  
Flora Macsi ◽  
...  
Keyword(s):  
Toxic Effect ◽  
Self Assembly ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Retinal Tissue ◽  
Age Related ◽  
Aβ Aggregation ◽  
And Function ◽  
The Impact

AbstractAmyloid-β (Aβ), reported as a significant constituent of drusen, was implicated in the pathophysiology of age-related macular degeneration (AMD), yet the identity of the major pathogenic Aβ species in the retina has remained hitherto unclear. Here, we examined the in-vivo retinal impact of distinct supramolecular assemblies of Aβ. Fibrillar (Aβ40, Aβ42) and oligomeric (Aβ42) preparations showed clear biophysical hallmarks of amyloid assemblies. Measures of retinal structure and function were studied longitudinally following intravitreal administration of the various Aβ assemblies in rats. Electroretinography (ERG) delineated differential retinal neurotoxicity of Aβ species. Oligomeric Aβ42 inflicted the major toxic effect, exerting diminished ERG responses through 30 days post injection. A lesser degree of retinal dysfunction was noted following treatment with fibrillar Aβ42, whereas no retinal compromise was recorded in response to Aβ40 fibrils. The toxic effect of Aβ42 architectures was further reflected by retinal glial response. Fluorescence labelling of Aβ42 species was used to detect their accumulation into the retinal tissue. These results provide conceptual evidence of the differential toxicity of particular Aβ species in-vivo, and promote the mechanistic understanding of their retinal pathogenicity. Stratifying the impact of pathological Aβ aggregation in the retina may merit further investigation to decipher the pathophysiological relevance of processes of molecular self-assembly in retinal disorders.

scholarly journals Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Majda Hadziahmetovic ◽  
Goldis Malek
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Clinical Care ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.

scholarly journals Sejtszintű képalkotás a retina in vivo vizsgálatában: jelen és jövő

2021 ◽  
Vol 162 (22) ◽  
pp. 851-860
Author(s):  
András Végh ◽  
Dániel Péter Magda ◽  
Ferenc Kilin ◽  
Anita Csorba ◽  
Mikós Resch ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Clinical Examination ◽  
Cell Types ◽  
Age Related Macular Degeneration ◽  
Everyday Clinical Practice ◽  
Retinal Tissue ◽  
Age Related ◽  
Examination Methods ◽  
Ganglion Cell Death

Összefoglaló. A látószerv különböző betegségei, valamint egyes szisztémás megbetegedések részben vagy kifejezetten az ideghártya károsodásával járnak. A patológia segítségével ma már tudjuk, hogy ezek a betegségek a retina mely rétegének vagy rétegeinek elváltozásait okozzák: míg az időskori maculadegeneratio a külső retinában található fotoreceptorokat érinti kifejezetten a fovea centralis területén, addig a glaucoma a belső retina ganglionsejtjeinek pusztulásával, valamint e sejtek opticusrostjainak károsodásával jár a stratum ganglionaréban és a stratum neurofibrarumban. Az emberi retina sejtjei azonban egyelőre nem maradéktalanul karakterizáltak, az egyes sejttípusok számát csak becsülni tudjuk, így nem írhatók le az egyes sejtszintű elváltozások sem kellő pontossággal. A szövettani feldolgozás és vizsgálat megfelelő részletességgel tájékoztat a diagnózisról és az elváltozás súlyosságáról, értelemszerűen azonban ez a módszer in vivo nem használható a mindennapi klinikai gyakorlatban. A sejtszintű elváltozások ismerete az egyes kórképekben felvetette és szükségessé tette olyan in vivo, a klinikumban is alkalmazható vizsgálómódszerek kifejlesztését, amelyek lehetőséget nyújtanak a retina neurális és egyéb sejtjeinek celluláris és szubcelluláris szintű vizsgálatára, ideértve a vér alakos elemeit is, amelyek egészséges vagy neovascularis eredetű erekben áramlanak. A jelenleg is használt klinikai vizsgálatok mellett ezek a képalkotó módszerek segítségül szolgálhatnak a diagnózis megerősítésében vagy elvetésében, emellett az elváltozás súlyosságának megítélésében, valamint a progresszió vagy remisszió monitorozásában. Orv Hetil. 2021; 162(22): 851–860. Summary. Diseases of the visual system as well as many systemic illnesses are usually associated with retinal damage. With the help of pathology, we can clearly identify the affected layer(s): while age-related macular degeneration mostly damages the photoreceptors in the outer retina at the central fovea, glaucoma promotes ganglion cell death in the ganglion cell layer and damages respective neural fibers. However, the diverse cell types of the human retina have not been fully characterized yet, thus in most cases our knowledge on cellular pathologies is not precise enough. While histopathological preparation and examination of the retinal tissue provide more detailed information about the diagnosis and the severity of the condition, unfortunately, it cannot be used in vivo in everyday clinical practice. Our understanding of the cellular changes in different diseases has revealed a need for new everyday clinical examination methods that can be used in vivo to asses cellular and subcellular changes in neural and other cells of the retina, such as blood cells flowing in healthy vessels or in vessels of neovascular origin. In addition to the currently used clinical examination methods, these imaging methods could help confirm or dismiss diagnoses, assess the severity of a condition, and monitor disease progression or remission. Orv Hetil. 2021; 162(22): 851–860.

scholarly journals Retinal Tissue Develops an Inflammatory Reaction to Tobacco Smoke and Electronic Cigarette Vapor in Mice

2021 ◽  
Author(s):  
Feng Wang ◽  
Stefan Hadzic ◽  
Elsa T. Roxlau ◽  
Baerbel Fuehler ◽  
Annabella Janise-Libawski ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Reaction ◽  
Electronic Cigarette ◽  
Age Related Macular Degeneration ◽  
Controlled Study ◽  
Cigarette Smoke Exposure ◽  
Retinal Tissue ◽  
Age Related

Abstract Cigarette smoke has been identified as a major risk factor for the development of age-related macular degeneration (AMD). As an alternative of conventional cigarette (C-cigarette), electronic cigarette (E-cigarette) has been rapidly promoted and used globally. The increasing usage of E-cigarette raises concerns with regard to long-term consequences related to retinal tissue. In the present study, a controlled study in mice models was conducted to probe the comprehensive effects of E-cigarette on retina, RPE and choroid tissues by (1) comparing the effect of C-cigarette smoke and E-cigarette smoke on retina; (2) determining the effects of E-cigarette vapor on the RPE and analyzing the changes with regard to inflammatory and angiogenic mediators in retina/RPE/choroid. The data showed that C-cigarette smoke exposure promoted an inflammatory reaction in the retina in vivo. Mice exposed to E-cigarette (nicotine-free) vapor developed inflammatory and angiogenic reactions more pronounced in RPE and choroid, while nicotine-containing E-cigarette vapor caused even a more serious reaction. Both, inflammatory and pro-angiogenic reactions increased with the extension of exposure time. These results demonstrate that exposure to C-cigarette smoke is harmful to the retina. Likewise, the exposure to E-cigarette vapor (with or without nicotine) increases the occurrence and progression of inflammatory and angiogenic stimuli in the retina, which might be similar effects causing the onset of wet AMD in humans.

Investigation of anti-Alzheimer’s activity of aqueous extract of areca nuts (Areca catechu L.): In vitro and in vivo studies

2021 ◽  
Vol 20 (4) ◽  
pp. 406-415
Author(s):  
Mahboubeh Bozorgi ◽  
◽  
Zahra Najafi ◽  
Sahar Omidpanah ◽  
Arash Sadri ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
In Vivo Studies ◽  
Memory Impairments ◽  
Age Related ◽  
Areca Catechu ◽  
Aβ Aggregation

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Sever cognitive and memory impairments, huge increase in the prevalence of the disease, and lacking definite cure have absorbed worldwide efforts to develop therapeutic approaches. Since many drugs have failed in the clinical trials due to multifactorial nature of AD, symptomatic treatments are still in the center attention and now, nootropic medicinal plants have been found as versatile ameliorators to reverse memory disorders. In this work, anti-Alzheimer’s activity of aqueous extract of areca nuts (Areca catechu L.) was investigated via in vitro and in vivo studies. It depicted good amyloid β (Aβ) aggregation inhibitory activity, 82% at 100 µg/mL. In addition, it inhibited beta-secretase 1 (BACE1) with IC50 value of 19.03 µg/mL. Evaluation of neuroprotectivity of the aqueous extract of the plant against H2O2-induced cell death in PC12 neurons revealed 84.5% protection at 1 µg/mL. It should be noted that according to our results obtained from Morris Water Maze (MWM) test, the extract reversed scopolamine-induced memory deficit in rats at concentrations of 1.5 and 3 mg/kg.

The Impact of Depression in Older Adults with Age-Related Macular Degeneration

2002 ◽  
Vol 96 (6) ◽  
pp. 399-406 ◽  
Author(s):  
Robin J. Casten ◽  
Barry W. Rovner ◽  
Susan E. Edmonds
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
General Function ◽  
Depressed Patients ◽  
Age Related ◽  
Dsm Iv ◽  
And Function ◽  
The Impact ◽  
The Relationship

This study examined how depression impacts age-related macular degeneration (AMD) disability among 114 elderly AMD patients. Results indicated that 49 patients met DSM-IV criteria for syndromal depression, and that visual acuity was the only variable significantly associated with vision-specific function. For general function, health was significant, and the relationship between visual acuity and function was only significant for depressed patients. Given that AMD results in high rates of depression and that depression exacerbates physical disability in AMD, devising optimal ways to identify and treat depressed patients in ophthalmology clinics is clearly important.

scholarly journals Carrot solution culture bioproduction of uniformly labeled 13C-lutein and in vivo dosing in non-human primates

2016 ◽  
Vol 242 (3) ◽  
pp. 305-315 ◽  
Author(s):  
Joshua W Smith ◽  
Randy B Rogers ◽  
Sookyoung Jeon ◽  
Stanislav S Rubakhin ◽  
Lin Wang ◽  
...  
Keyword(s):  
Liquid Solution ◽  
Macaque Monkey ◽  
Solution Culture ◽  
Age Related Macular Degeneration ◽  
Tracer Studies ◽  
Human Diet ◽  
Age Related ◽  
High Enrichment ◽  
And Function

Lutein is a xanthophyll abundant in nature and most commonly present in the human diet through consumption of leafy green vegetables. With zeaxanthin and meso-zeaxanthin, lutein is a component of the macular pigment of the retina, where it protects against photooxidation and age-related macular degeneration. Recent studies have suggested that lutein may positively impact cognition throughout the lifespan, but outside of the retina, the deposition, metabolism, and function(s) of lutein are poorly understood. Using a novel botanical cell culture system ( Daucus carota), the present study aimed to produce a stable isotope lutein tracer for use in future investigations of dietary lutein distribution and metabolism. Carrot cultivars were initiated into liquid solution culture, lutein production conditions optimized, and uniformly labeled 13C-glucose was provided as the sole media carbon source for four serial growth cycles. Lutein yield was 2.58 ± 0.24 µg/g, and mass spectrometry confirmed high enrichment of 13C: 64.9% of lutein was uniformly labeled and 100% of lutein was labeled on at least 37 of 40 possible carbons. Purification of carrot extracts yielded a lutein dose of 1.92 mg with 96.0 ± 0.60% purity. 13C-lutein signals were detectable in hepatic extracts of an adult rhesus macaque monkey ( Macaca mulatta) dosed with 13C-lutein, but not in hepatic samples collected from control animals. This novel botanical biofactory approach can be used to produce sufficient quantities of highly enriched and pure 13C-lutein doses for use in tracer studies investigating lutein distribution, metabolism, and function.

scholarly journals Neuroinflammatory changes increase the impact of stressors on neuronal function

2009 ◽  
Vol 37 (1) ◽  
pp. 303-307 ◽  
Author(s):  
Alessia Piazza ◽  
Marina A. Lynch
Keyword(s):  
Neurodegenerative Diseases ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Experimental Conditions ◽  
Age Related ◽  
Increased Risk ◽  
Aβ Amyloid ◽  
The Impact

In the last few years, several research groups have reported that neuroinflammation is one feature common to several neurodegenerative diseases and that similar, although perhaps less profound, neuroinflammatory changes also occur with age. Age is the greatest risk factor in many neurodegenerative diseases, and the possibility exists that the underlying age-related neuroinflammation may contribute to this increased risk. Several animal models have been used to examine this possibility, and it is now accepted that, under experimental conditions in which microglial activation is up-regulated, responses to stressors are exacerbated. In the present article, these findings are discussed and data are presented from in vitro and in vivo experiments which reveal that responses to Aβ (amyloid β-peptide) are markedly up-regulated in the presence of LPS (lipopolysaccharide). These, and previous findings, point to a vulnerability associated with inflammation and suggest that, even though inflammation may not be the primary cause of neurodegenerative disease, its treatment may decelerate disease progression.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

scholarly journals The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Risk Factors ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Vascular Risk ◽  
Average Volume ◽  
Central Ring ◽  
Age Related ◽  
The Impact ◽  
Wet Amd

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

scholarly journals 4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Age Related ◽  
Tnf Α ◽  
Cox 2

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

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