Age-Related Macular Degeneration and Mitochondria-Associated Autoantibodies: A Review of the Specific Pathogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1624 - 1624

Опубликована: Янв. 28, 2024

Age-related macular degeneration (AMD) is a severe retinal disease that causes irreversible visual loss and blindness in elderly populations worldwide. The pathological mechanism of AMD complex, involving the interactions multiple environmental genetic factors. A poor understanding leads to limited treatment options few effective prevention methods. discovery autoantibodies patients provides an opportunity explore pathogenesis direction disease. This review focuses on mitochondria-associated summarizes functional roles mitochondria under physiological conditions their alterations during states. Additionally, it discusses crosstalk between other organelles, as well mitochondria-related therapeutic strategies AMD.

Язык: Английский

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Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea

Antioxidants, Год журнала: 2024, Номер 13(7), С. 878 - 878

Опубликована: Июль 22, 2024

Obstructive sleep apnea (OSA) is a disorder characterized by intermittent complete or partial occlusion of the airway. Despite recognized association between OSA and glaucoma, nature underlying link remains unclear. In this study, we investigated whether mild induces morphological, inflammatory, metabolic changes in retina resembling those seen glaucoma using rat model known as chronic hypoxia (CIH). Rats were randomly assigned to either normoxic CIH groups. The group was exposed periodic during its phase with oxygen reduction from 21% 10% reoxygenation 6 min cycles over 8 h/day. eyes subsequently enucleated, then retinas evaluated for retinal ganglion cell number, oxidative stress, inflammatory markers, changes, hypoxic response modulation immunohistochemistry, multiplex assays, capillary electrophoresis. Statistically significant differences observed groups stress inflammation, resulting increased HIF-1α protein levels, higher marker 8-OHdG, TNF-α. Pyruvate dehydrogenase kinase-1 significantly reduced CIH. No found number. Our findings suggest that upregulation retina, akin early-stage glaucoma.

Язык: Английский

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Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Glaucoma polygenic risk scores (PRS) effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study the UK Biobank, we investigated whether plasma metabolites enhanced prediction if metabolomic signature of high-genetic existed. Logistic regression models incorporating 168 NMR-based into PRS-based assessments were developed, multiple comparison corrections applied. While weakly predicted (Area Under Curve=0.579), they offered modest improvement PRS-only-based (P=0.004). We identified associated top decile, elevated glycolysis-related metabolites—lactate (P=8.8E-12), pyruvate (P=1.9E-10), citrate (P=0.02)—linked reduced prevalence. These combined significantly modified PRS-glaucoma relationship (P interaction =0.011). Higher total metabolite levels within highest quartile corresponded lower prevalence (Odds Ratio vs. lowest =0.71, 95% Confidence Interval [CI]=0.64–0.80). As is foundational linking glycolysis tricarboxylic acid cycle metabolism ATP generation, pursued experimental validation for putative biomarker human-relevant Mus musculus model. Dietary mitigated intraocular pressure (P=0.002) optic nerve damage (P<0.0003) Lmx1b V265D mice. findings highlight protective role pyruvate-related against suggest potential avenues therapeutic intervention.

Язык: Английский

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Exploring Endothelial Cell Dysfunction’s Impact on the Brain-Retina Microenvironment Connection: Molecular Mechanisms and Implications

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

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Retinal physiology in metabolic syndrome

Advances in genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma

Опубликована: Март 11, 2025

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced prediction if metabolomic signature high-genetic-risk existed. Logistic regression models incorporating 168 NMR-based into PRS-based assessments were developed, multiple comparison corrections applied. While weakly predicted (Area Under Curve = 0.579), they offered marginal improvement PRS-only-based (p=0.004). We identified associated top decile, elevated glycolysis-related metabolites-lactate (p=8.8E-12), pyruvate (p=1.9E-10), citrate (p=0.02)-linked reduced prevalence. These combined significantly modified PRS-glaucoma relationship (Pinteraction 0.011). Higher total metabolite levels within highest quartile corresponded lower prevalence (Odds Ratiohighest vs. lowest quartile=0.71, 95% Confidence Interval 0.64-0.80). As is foundational linking glycolysis tricarboxylic acid cycle metabolism ATP generation, pursued experimental validation for putative biomarker human-relevant Mus musculus model. Dietary mitigated intraocular pressure (p=0.002) optic nerve damage (p<0.0003) Lmx1bV265D mice. findings highlight protective role pyruvate-related against suggest potential avenues therapeutic intervention.

Язык: Английский

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Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma

Опубликована: Март 11, 2025

Glaucoma polygenic risk scores (PRS) effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study the UK Biobank, we investigated whether plasma metabolites enhanced prediction if metabolomic signature of high-genetic existed. Logistic regression models incorporating 168 NMR-based into PRS-based assessments were developed, multiple comparison corrections applied. While weakly predicted (Area Under Curve=0.579), they offered modest improvement PRS-only-based (P=0.004). We identified associated top decile, elevated glycolysis-related metabolites—lactate (P=8.8E-12), pyruvate (P=1.9E-10), citrate (P=0.02)—linked reduced prevalence. These combined significantly modified PRS-glaucoma relationship (P interaction =0.011). Higher total metabolite levels within highest quartile corresponded lower prevalence (Odds Ratio vs. lowest =0.71, 95% Confidence Interval [CI]=0.64–0.80). As is foundational linking glycolysis tricarboxylic acid cycle metabolism ATP generation, pursued experimental validation for putative biomarker human-relevant Mus musculus model. Dietary mitigated intraocular pressure (P=0.002) optic nerve damage (P<0.0003) Lmx1b V265D mice. findings highlight protective role pyruvate-related against suggest potential avenues therapeutic intervention.

Язык: Английский

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Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma

Опубликована: Март 28, 2025

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced prediction if metabolomic signature high-genetic-risk existed. Logistic regression models incorporating 168 NMR-based into PRS-based assessments were developed, multiple comparison corrections applied. While weakly predicted (Area Under Curve=0.579), they offered marginal improvement PRS-only-based (P=0.004). We identified associated top decile, elevated glycolysis-related metabolites—lactate (P=8.8E-12), pyruvate (P=1.9E-10), citrate (P=0.02)—linked reduced prevalence. These combined significantly modified PRS-glaucoma relationship (P interaction =0.011). Higher total metabolite levels within highest quartile corresponded lower prevalence (Odds Ratio vs. lowest =0.71, 95% Confidence Interval=0.64–0.80). As is foundational linking glycolysis tricarboxylic acid cycle metabolism ATP generation, pursued experimental validation for putative biomarker human-relevant Mus musculus model. Dietary mitigated intraocular pressure (P=0.002) optic nerve damage (P<0.0003) Lmx1b V265D mice. findings highlight protective role pyruvate-related against suggest potential avenues therapeutic intervention.

Язык: Английский

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Pyruvate and related energetic metabolites modulate resilience against high genetic risk for glaucoma

eLife, Год журнала: 2025, Номер 14

Опубликована: Апрель 24, 2025

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced prediction if metabolomic signature high-genetic-risk existed. Logistic regression models incorporating 168 NMR-based into PRS-based assessments were developed, multiple comparison corrections applied. While weakly predicted (Area Under Curve = 0.579), they offered marginal improvement PRS-only-based (p=0.004). We identified associated top decile, elevated glycolysis-related metabolites—lactate (p=8.8E-12), pyruvate (p=1.9E-10), citrate (p=0.02)—linked reduced prevalence. These combined significantly modified PRS-glaucoma relationship (P interaction 0.011). Higher total metabolite levels within highest quartile corresponded lower prevalence (Odds Ratio vs. lowest =0.71, 95% Confidence Interval 0.64–0.80). As is foundational linking glycolysis tricarboxylic acid cycle metabolism ATP generation, pursued experimental validation for putative biomarker human-relevant Mus musculus model. Dietary mitigated intraocular pressure (p=0.002) optic nerve damage (p<0.0003) Lmx1b V265D mice. findings highlight protective role pyruvate-related against suggest potential avenues therapeutic intervention.

Язык: Английский

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The Impact of Blood and Urine Biomarkers on Age-Related Macular Degeneration: Insights from Mendelian Randomization and Cross-sectional Study from NHANES

Biological Procedures Online, Год журнала: 2024, Номер 26(1)

Опубликована: Июнь 25, 2024

Abstract Introduction Age-related macular degeneration (AMD) is a leading cause of blindness, affecting millions worldwide. Its complex pathogenesis involves variety risk factors, including lipid metabolism and inflammation. This study aims to elucidate the causal relationships between biomarkers related these processes AMD, leveraging Mendelian randomization (MR) cross-sectional analysis from National Health Nutrition Examination Survey (NHANES). Method We conducted two-phase study, initially using MR explore causality 35 various AMD subtypes, followed by observational with NHANES data validate findings. Results identified protective role TG factor HDL-C CRP in development. corroborated findings, highlighting nuanced relationship AMD. Notably, metabolism-related showed stronger associations early whereas CRP’s significance was pronounced late Conclusion comprehensive analysis, combining data, reinforces importance inflammation AMD’s etiology. Future research should further investigate biomarkers’ mechanisms their potential as therapeutic targets for prevention treatment.

Язык: Английский

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