The Inappropriate Photoreceptor Depolarization May Give Rise to Age-Related Macular Degeneration: Clinical Evidence

Published: Feb. 14, 2025

Age-related Macular Degeneration (AMD) is a complex, multifactorial, progressive retinal disease that affects millions of people worldwide. Alterations in phototransduction, renewal the outer segments photoreceptors, visual transduction and retinol metabolism have major impact on health. Mutations within any molecules responsible for these processes cause different types degenerative diseases. Increase membrane potential caused by accidental binding to foreign molecule, increased temperature or ocular pressure could trigger an electrochemical overload photoreceptor which would be inappropriately depolarized. The signs this process are clearly visible with Optical Coherence Tomography (OCT): hyper-reflective vertical lines cross choroid at points interruption ellipsoid zone resulting atrophy compromise hematoretinal barrier. occasional finding represent first clinical sign subsequently give rise those events characterizing AMD.

Language: Английский

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Berberine-mediated REDD1 down-regulation ameliorates senescence of retinal pigment epithelium by interrupting the ROS-DDR positive feedback loop

Phytomedicine, Journal Year: 2022, Volume and Issue: 104, P. 154181 - 154181

Published: May 24, 2022

Language: Английский

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Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(2), P. 1500 - 1518

Published: Feb. 9, 2023

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used prevent process in humans, lutein. This study aims determine differences expression patterns of pyroptosis genes senescent human retinal epithelial cell line ARPE-19 Changes pyroptosis-related were assessed by oligonucleotide microarrays, and results validated real-time RT-qPCR. The microarray analysis showed seven transcripts differentially expressed both H2O2-treated cells versus controls lutein/H2O2-treated compared (FC > 2.0). Depending on lutein, H2O2, or co-treatment statistically significant TXNIP, CXCL8, BAX, CASP1 confirmed RT-qPCR (p < 0.05). A STRING database that proteins encoded analyzed form strong interaction network 0.001). These data indicate lutein modulates level genes, may be useful development new methods preventing pathway activation future.

Language: Английский

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Peroxynitrite: A tale of two radicals

Redox Biochemistry and Chemistry, Journal Year: 2024, Volume and Issue: 10, P. 100038 - 100038

Published: Aug. 3, 2024

The published syntheses of peroxynitrite from azide, nitrite, amylnitrite, hydroxylamine, nitrogen monoxide, and ammonia are discussed. With one exception, all these yield contaminated with nitrate nitrite as well reactants. rate constant for the reaction monoxide superoxide has been determined by pulse radiolysis flash photolysis. In studies, formation reactants may be rate-limiting could lead to underestimation second-order constant. conditions photolysis experiments can chosen minimize conflict between reactant half-life, thus 1.6 × 1010 M−1s−1 is preferred. toxicity attributed mainly its rapid carbon dioxide oxidizing trioxidocarbonate(•1−) radicals.

Language: Английский

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Fisetin Attenuated Oxidative Stress-Induced Cellular Damage in ARPE-19 Human Retinal Pigment Epithelial Cells Through Nrf2-Mediated Activation of Heme Oxygenase-1

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 16, 2022

Fisetin is a kind of bioactive flavonol, widely present in various fruits such as strawberries and apples, known to act potent free radical scavenger. However, the mechanism action related antioxidant activity this compound human retinal pigment epithelial (RPE) cells not precisely known. In study, we aimed investigate whether fisetin could attenuate oxidative stress-induced cytotoxicity on RPE ARPE-19 cells. To mimic stress, were treated with hydrogen peroxide (H 2 O ), significantly inhibited H -induced loss cell viability increase intracellular reactive oxygen species (ROS) production. also markedly attenuated DNA damage apoptosis -treated Moreover, mitochondrial dysfunction was alleviated presence indicated by preservation membrane potential, Bcl-2/Bax expression ratio, suppression cytochrome c release into cytoplasm. addition, enhanced phosphorylation nuclear translocation factor erythroid (Nrf2), which associated increased heme oxygenase-1 (HO-1). HO-1 inhibitor, zinc protoporphyrin, reversed protective effect against -mediated injury. Therefore, our results suggest that Nrf2-mediated activation enzyme may play an important role ROS scavenging cells, contributing amelioration ocular disorders.

Language: Английский

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Hydrogen peroxide-induced oxidative damage and protective role of peroxiredoxin 6 protein via EGFR/ERK signaling pathway in RPE cells

Frontiers in Aging Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: July 17, 2023

Introduction Damage to retinal pigment epithelium (RPE) cells caused by oxidative stress is closely related the pathogenesis of several blinding diseases, such as age-related macular degeneration (AMD), retinitis pigmentosa, and other inherited degenerative conditions. However, mechanisms this process are poorly understood. Hence, goal study was investigate hydrogen peroxide (H 2 O )-induced damage protective role peroxiredoxin 6 (PRDX6) protein via EGFR/ERK signaling pathway in RPE cells. Methods Cells from a human cell line (ARPE-19 cells) were treated with H , then viability assessed using methyl thiazolyl tetrazolium assay. Cell death reactive oxygen species (ROS) detected flow cytometry. The levels PRDX6, epidermal growth factor receptor (EGFR), P38 mitogen-activated kinase (P38MAPK), c-Jun N-terminal (JNK), extracellular signal-regulated (ERK) Western blot PRDX6 EGFR also immunofluorescence staining. Results Our results show that inhibited viability, induced death, increased ROS ARPE-19 It found decreased EGFR, phosphorylated ERK but P38MAPK JNK. overexpression attenuate -induced inhibition production expression alleviated decrease ERK. Moreover, factor-induced partially blocked overexpression. Discussion findings indicate protects decreasing blocking stress. Therefore, shows promise therapeutic target for prevention associated diseases.

Language: Английский

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A review on the techno‐functional, biological, and health‐promoting properties of hempseed‐derived proteins and peptides

Journal of Food Biochemistry, Journal Year: 2022, Volume and Issue: 46(7)

Published: March 21, 2022

Protein-energy malnutrition is a global challenge that demands urgent attention, especially with the increasing population growth and unmatched food security plans. One strategy to expand list of protein sources, such as neglected underutilized crops, high content. A good number plant proteins, in addition their nutritional benefits, exert therapeutic properties seen seeds derived from legumes emerging sources hemp. In this review, transepithelial transport, functional, biological hempseed proteins (HSPs) peptides were discussed. The review also described potential safety issues incorporating hempseeds products. Due multitargeted effects hempseed-derived against many chronic diseases, functional properties, current knowledge shows has tremendous for nutraceutical applications. Practical applications alarming rate attendant health consequences demand underexploited nutrient-rich crops should be incorporated part our common dietary sources. Among these gaining attention an source promising prevention management diseases diabetes, hypertension, cancer, hypercholesterolemia, obesity, whose etiology involves oxidative stress inflammation. Fortunately, growing body research evidence demonstrating reservoir potentials curbing life-threatening diseases.

Language: Английский

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Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11357 - 11357

Published: Oct. 22, 2024

Neovascular age-related macular degeneration (nAMD), a leading cause of blindness in older adults, presents challenging pathophysiology involving choroidal neovascularization (CNV) and retinal degeneration. Current treatments relying on intravitreal (IVT) administration anti-angiogenic agents are costly moderate effectiveness. Metformin, the common anti-diabetic drug, has been associated with decreased odds developing AMD. Studies have shown that metformin can mitigate cellular aging, neoangiogenesis, inflammation across multiple diseases. This preclinical study assessed metformin's impact vessel growth using explants before exploring IVT effects laser-induced CNV light-induced C57BL/6J BALB/cJ mice, respectively. Metformin reduced new dose-dependent relationship. Following laser induction, suppressed peripheral infiltration IBA1

Language: Английский

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Chaperones vs. oxidative stress in the pathobiology of ischemic stroke

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Dec. 11, 2024

As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in Liebig's barrel cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting quality healthy stressful conditions. This machinery, namely chaperones, assists folding, refolding, utilization client proteins. The functions chaperones are especially important for brain cells, which highly sophisticated terms structural functional organization. Molecular known to exert beneficial effects diseases including one most threatening widespread pathologies, ischemic stroke. However, whether how they antioxidant defense stroke remains unclear. Herein, we discuss shown fight oxidative stress mechanisms their action. stroke, during intense production free radicals, molecular preserve by interacting with oxidized proteins, regulating imbalanced mitochondrial function, directly fighting stress. For instance, cells recruit Hsp60 Hsp70 provide proper folding newly synthesized proteins-these factors required early response refold damaged polypeptides. Additionally, upregulates some dedicated pathways such as FOXO3 signaling. Small HSPs decrease via attenuation function through involvement regulation Nrf- (Hsp22), Akt Hippo (Hsp27) signaling well mitophagy (Hsp27, Hsp22). A similar has also been proposed Sigma-1 receptor, contributing function. Some can prevent excessive formation reactive oxygen species whereas Hsp90 suggested be responsible pro-oxidant Finally, heat-resistant obscure (Hero) able shield thus preventing possible oxidation.

Language: Английский

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Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina?

Antioxidants, Journal Year: 2022, Volume and Issue: 11(6), P. 1132 - 1132

Published: June 9, 2022

Vitamins C and E zeaxanthin are components of a supplement tested in large clinical trial-Age-Related Eye Disease Study 2 (AREDS2)-and it has been demonstrated that they can inhibit the progression age-related macular degeneration. The aim this study was to determine optimal combinations these antioxidants prevent phototoxicity mediated by vitamin A aldehyde (ATR), which accumulate photoreceptor outer segments (POS) upon exposure light. We used cultured retinal pigment epithelial cells ARPE-19 liposomes containing unsaturated lipids ATR as model POS. Cells and/or were enriched with lipophilic antioxidants, whereas ascorbate added just before Supplementing single had only minor effect on phototoxicity, but protection substantially increased presence both ways supplementation. Combinations α-tocopherol provided substantial protection, enhancing cell viability from ~26% absence ~63% 4 µM 80 α-tocopherol, protective further ~69% 0.5 mM ascorbate. disappeared at concentration 1 mM, exacerbated phototoxicity. Zeaxanthin or partly ameliorated cytotoxic effects. Altogether, our results suggest combination includes upper levels achievable diet supplementations, needs be four-fold smaller than vitreous. physiological relevance is discussed.

Language: Английский

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