scholarly journals Associations Between Serum Lutein and Human Gut Microbiota (P02-004-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Andrew Dinsmoor ◽  
Sharon Thompson ◽  
Caitlyn Edwards ◽  
Nicholas Burd ◽  
Naiman Khan ◽  
...  
Keyword(s):  
Dietary Intervention ◽  
Adult Population ◽  
Venous Blood ◽  
Age Related Macular Degeneration ◽  
Leafy Vegetables ◽  
Whole Body ◽  
Rrna Gene ◽  
Protective Effects ◽  
Food Record ◽  
Age Related

Abstract Objectives Lutein is a carotenoid found in green leafy vegetables, avocados, and eggs, and is purported to have protective effects against age-related macular degeneration (AMD) as well as benefits for visual and cognitive health. Recent studies have indicated significant variation in serum lutein among individuals and that gastrointestinal (GI) microbial profile may potentially contribute to lutein status. However, the extent to which the GI microbiota contribute to lutein is unclear. The current study aimed to determine GI microbial predictors of serum lutein in a healthy young adult population. Methods Among adults ages 25–45 years (N = 105), venous blood was collected following a 10-hour fast. Serum lutein was determined using HPLC. Fecal DNA was extracted and the V4 region of the 16S rRNA gene was amplified. Amplicon sequence variants were assigned using the GreenGenes 13-8 database and DADA2, followed by analysis in QIIME2 and LDA Effect Size (LEfSe). Participants underwent DXA scan for whole body % fat (%Fat) and completed a 7-day food record to assess lutein consumption. Demographic information on participant's age and sex was also assessed and included in the statistical models. Results Four genera (Dialister, Ruminococcus, Gemmiger, and Phascolarctobacterium) and two species (Bacteroides eggerthii, Ruminococcus torques) were different between individuals in the highest and lowest quartiles of serum lutein. The genera Ruminococcus (Rho = −0.24, P = 0.02) and Phascolarctobacterium (Rho = −0.21, P = 0.03) and species R. torques (Rho = −0.35, P < 0.001) were inversely related to serum lutein. Linear regression modelling, adjusted for age, sex, %Fat, and dietary lutein, revealed that R. torques was the only significant predictor of serum lutein concentrations, accounting for 8.4% of the variance. Conclusions Our results reveal that individuals with lower serum lutein concentrations have a higher relative abundance of R. torques than those with higher lutein concentrations. As R. torques has been shown to be elevated in those with AMD, it is possible the relationship between this microbe and lutein is evident earlier in adulthood. However, further dietary intervention trials are warranted to clarify the relations among R. torques and serum lutein concentrations. Funding Sources This work was supported by funds provided by the Department of Kinesiology and Community Health at the University of Illinois and the USDA National Institute of Food and Agriculture, Hatch Project 1009249. Partial support was also provided by the Hass Avocado Board.

scholarly journals Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687

2021 ◽  
Author(s):  
Marc Vanhove ◽  
Jean-Marc Wagner ◽  
Bernard Noppen ◽  
Bart Jonckx ◽  
Elke Vermassen ◽  
...  
Keyword(s):  
General Circulation ◽  
Pharmacokinetic Model ◽  
Systemic Exposure ◽  
Age Related Macular Degeneration ◽  
Whole Body ◽  
Pharmacological Agents ◽  
Age Related ◽  
Pharmacokinetic Properties ◽  
High Concentrations ◽  
Systemic Compartment

AbstractIntravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.

scholarly journals Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 309
Author(s):  
Pachiappan Arjunan ◽  
Radhika Swaminathan ◽  
Jessie Yuan ◽  
Mohamed Elashiry ◽  
Amany Tawfik ◽  
...  
Keyword(s):  
Murine Model ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Periodontal Pathogen ◽  
Fundus Photography ◽  
Mouse Retina ◽  
Rrna Gene ◽  
Age Related ◽  
Periodontal Infection

Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected Pg and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.

scholarly journals Potential TSPO Ligand and Photooxidation Quencher Isorenieratene from Arctic Ocean Rhodococcus sp. B7740

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 316 ◽  
Author(s):  
Yashu Chen ◽  
Mengyao Guo ◽  
Jifang Yang ◽  
Jigang Chen ◽  
Bijun Xie ◽  
...  
Keyword(s):  
Arctic Ocean ◽  
Oxidation Process ◽  
Cell Model ◽  
Age Related Macular Degeneration ◽  
The Arctic ◽  
Protective Effects ◽  
Uvb Radiation ◽  
Age Related ◽  
Active Natural ◽  
Rhodococcus Sp

Due to its special aromatic structure, isorenieratene is thought to be an active natural antioxidant and photo/UV damage inhibitor. In this work, isorenieratene that was extracted from Rhodococcus sp. B7740 isolated from the Arctic Ocean, showed excellent scavenging ability of both singlet oxygen and hydroxyl radical in the UVB-induced auto-oxidation process using the EPR method. Within an ARPE-19 cell model damaged by UVB radiation, isorenieratene showed fine protective effects (1.13 ± 0.03 fold) compared with macular xanthophylls (MXs) through upregulating of tspo. The molecular docking was firstly performed to investigate the interaction of isorenieratene with TSPO as a special ligand. Results showed isorenieratene might form a better binding conformation (S-score −8.5438) than MXs and indicate that isorenieratene not only can function as a direct antioxidant but also activate tspo in ARPE-19 cells. Thus, isorenieratene might ease the UV-related damages including age-related macular degeneration (AMD).

scholarly journals Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

2020 ◽  
Vol 21 (3) ◽  
pp. 704 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
Nadezhda V. Azbukina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Aqueous Humor ◽  
Rabbit Model ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Cyclooxygenase Inhibitor ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

scholarly journals Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Xia Zhao ◽  
Linlin Liu ◽  
Yizhou Jiang ◽  
Marta Silva ◽  
Xuechu Zhen ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Rpe Cells ◽  
Mitochondria Membrane Potential ◽  
Ampk Pathway ◽  
Age Related ◽  
Diabetes Drug

Age-related macular degeneration (AMD) is a leading cause of blindness with limited effective treatment. Although the pathogenesis of this disease is complex and not fully understood, the oxidative damage caused by excessive reactive oxygen species (ROS) in retinal pigment epithelium (RPE) has been considered as a major cause. Autophagy is essential for the degradation of cellular components damaged by ROS, and its dysregulation has been implicated in AMD pathogenesis. Therefore, strategies aiming to boost autophagy could be effective in protecting RPE cells from oxidative damage. Metformin is the first-line anti-type 2 diabetes drug and has been reported to stimulate autophagy in many tissues. We therefore hypothesized that metformin may be able to protect RPE cells against H2O2-induced oxidative damage by autophagy activation. In the present study, we found that metformin attenuated H2O2-induced cell viability loss, apoptosis, elevated ROS levels, and the collapse of the mitochondria membrane potential in D407 cells. Autophagy was stimulated by metformin, and inhibition of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) or knockdown of Beclin1 and LC3B blocked the protective effects of metformin. In addition, we showed that metformin could activate the AMPK pathway, whereas both pharmacological and genetic inhibitions of AMPK blocked the autophagy-stimulating and protective effects of metformin. Metformin conferred a similar protection against H2O2-induced oxidative damage in primary cultured human RPE cells. Taken together, these results demonstrate that metformin could protect RPE cells from H2O2-induced oxidative damage by stimulating autophagy via the activation of the AMPK pathway, supporting its potential use in the prevention and treatment of AMD.

scholarly journals The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution

2014 ◽  
Vol 2014 ◽  
pp. 1-22 ◽  
Author(s):  
Borut Poljšak ◽  
Rok Fink
Keyword(s):  
Oxidative Stress ◽  
Nitrosative Stress ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Age Related ◽  
Dietary Antioxidant ◽  
Polycyclic Aromatic ◽  
Antioxidant Supplements

Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example,β-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.

scholarly journals Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration

2019 ◽  
Vol 20 (13) ◽  
pp. 3367 ◽  
Author(s):  
Chawanphat Muangnoi ◽  
Umar Sharif ◽  
Pahweenvaj Ratnatilaka Na Bhuket ◽  
Pornchai Rojsitthisak ◽  
Luminita Paraoan
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Parent Drug ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Rpe Cells ◽  
Age Related ◽  
Potent Drug

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

scholarly journals Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 920
Author(s):  
Ayana Suzumura ◽  
Ryo Terao ◽  
Hiroki Kaneko
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Essential Fatty Acids ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Retinal Diseases ◽  
Protective Effects ◽  
Molecular Signaling ◽  
Age Related ◽  
Membrane Components

Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation.

scholarly journals Evaluation of Congo Red Staining in Degenerating Porcine Photoreceptors In Vitro: Protective Effects by Structural and Trophic Support

2018 ◽  
Vol 66 (9) ◽  
pp. 631-641 ◽  
Author(s):  
Camilla Mohlin ◽  
Dick Delbro ◽  
Anders Kvanta ◽  
Kjell Johansson
Keyword(s):  
Congo Red ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Structural Support ◽  
Age Related ◽  
Time Period

Congo red (CR) is a histological stain used for the detection of extracellular amyloids mediating various neurodegenerative diseases. Given that damaged photoreceptors appear to degenerate similarly to other nerve cells, CR staining was evaluated in experimentally injured porcine retina. CR staining appeared mostly as discrete cytosolic deposits with no obvious plaque formation during the investigated time period. Increases of CR labeling coincided temporally with the known accumulation of mislocalized opsins and increases of cell death. Coculture, either with human retinal pigment epithelium (ARPE) or human neural progenitor (ReN) cells, was accompanied by a significant reduction of CR labeling. Of particular interest was the reduction of CR labeling in cone photoreceptors, which are important for the perception of color and fine details and afflicted in age-related macular degeneration (AMD). Electron microscopy revealed inclusions in the inner segment, cell body, and occasionally synaptic terminals of photoreceptor cells in cultured specimens. Closer examinations indicated the presence of different types of inclusions resembling protein aggregates as well as inclusion bodies. The current results indicate that injury-related response resulted in accumulation of CR deposits in photoreceptor cells, and that trophic and/or structural support attenuated this response.

scholarly journals Effects of a Newly Developed Enzyme-Assisted Extraction Method on the Biological Activities of Fucoidans in Ocular Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 282 ◽  
Author(s):  
Philipp Dörschmann ◽  
Maria Dalgaard Mikkelsen ◽  
Thuan Nguyen Thi ◽  
Johann Roider ◽  
Anne S. Meyer ◽  
...  
Keyword(s):  
High Performance ◽  
Biological Activities ◽  
Alginate Lyase ◽  
Extraction Methods ◽  
Exchange Chromatography ◽  
Age Related Macular Degeneration ◽  
Saccharina Latissima ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Age Related

Fucoidans from brown seaweeds are promising substances as potential drugs against age-related macular degeneration (AMD). The heterogeneity of fucoidans requires intensive research in order to find suitable species and extraction methods. Ten different fucoidan samples extracted enzymatically from Laminaria digitata (LD), Saccharina latissima (SL) and Fucus distichus subsp. evanescens (FE) were tested for toxicity, oxidative stress protection and VEGF (vascular endothelial growth factor) inhibition. For this study crude fucoidans were extracted from seaweeds using different enzymes and SL fucoidans were further separated into three fractions (SL_F1-F3) by ion-exchange chromatography (IEX). Fucoidan composition was analyzed by high performance anion exchange chromatography (HPAEC) after acid hydrolysis. The crude extracts contained alginate, while two of the fractionated SL fucoidans SL_F2 and SL_F3 were highly pure. Cell viability was assessed with an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay in OMM-1 and ARPE-19. Protective effects were investigated after 24 h of stress insult in OMM-1 and ARPE-19. Secreted VEGF was analyzed via ELISA (enzyme-linked immunosorbent assay) in ARPE-19 cells. Fucoidans showed no toxic effects. In OMM-1 SL_F2 and several FE fucoidans were protective. LD_SiAT2 (Cellic®CTec2 + Sigma-Aldrich alginate lyase), FE_SiAT3 (Cellic® CTec3 + Sigma-Aldrich alginate lyase), SL_F2 and SL_F3 inhibited VEGF with the latter two as the most effective. We could show that enzyme treated fucoidans in general and the fractionated SL fucoidans SL_F2 and SL_F3 are very promising for beneficial AMD relevant biological activities.

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