EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(12), P. 4271 - 4271

Published: June 16, 2020

Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal (EndMT) are physiological processes required for normal embryogenesis. However, these can be hijacked in pathological conditions to facilitate tissue fibrosis cancer metastasis. In the eye, EMT EndMT play key roles pathogenesis of subretinal fibrosis, end-stage age-related macular degeneration (AMD) that leads profound permanent vision loss. Predominant fibrotic lesions matrix-producing mesenchymal cells believed originate from retinal pigment epithelium (RPE) and/or choroidal endothelial (CECs) through EndMT, respectively. Recent evidence suggests RPE may also implicated during early stages AMD. Transforming growth factor-beta (TGFβ) is a cytokine orchestrating both EndMT. Investigations molecular mechanisms underpinning AMD have myriad contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism mitochondrial dysfunction. Questions arise as differences derived two their distinct mechanistic contributions Detailed discussion on microenvironment highlights synergistic interactions between CECs augment vivo. Understanding differential regulatory networks dry wet forms aid development therapeutic strategies targeting potentially reverse aberrant cellular transdifferentiation processes, regenerate retina thus restore vision.

Language: Английский

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NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Sept. 16, 2021

Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD

Language: Английский

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The complement system in age-related macular degeneration

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(10), P. 4487 - 4505

Published: March 9, 2021

Age-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness affects mainly elderly population. AMD pathogenesis pathophysiology are incredibly complex due to structural cellular complexity variety risk factors molecular mechanisms that contribute onset progression. driven by combination genetic predisposition, natural ageing changes lifestyle factors, such as smoking or nutritional intake. The mechanism these interact converge towards not fully understood therefore drug discovery challenging, where no therapeutic attempt has been effective thus far. Genetic studies have identified complement system an important player AMD. Indeed, many variants cluster genes alternative pathway activation products elevated patients. Nevertheless, attempts treating via regulators yet successful, suggesting level could be predicted only from point view. In this review, we will explore role development main features AMD, including itself, inflammation, ECM stability, energy metabolism oxidative stress.

Language: Английский

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The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

Antioxidants, Journal Year: 2020, Volume and Issue: 9(4), P. 347 - 347

Published: April 23, 2020

Retinal cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress damage. Oxidative alters homeostasis elicits a protective response, which is most relevant in photoreceptors retinal ganglion cells, neurons with high metabolic rate are continuously subject to light/oxidative insults. We analyze how the alteration of cellular endogenous pathways for protection against leads dysfunction prevalent (age-related macular degeneration, glaucoma) as well rare genetic visual disorders (Retinitis pigmentosa, Leber hereditary optic neuropathy). also highlight some key molecular actors discuss potential therapies using antioxidants agents, modulators gene expression inducers cytoprotective signaling treat damaging effects ameliorate severe phenotypic symptoms multifactorial dystrophies.

Language: Английский

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Autophagy in age-related macular degeneration

Autophagy, Journal Year: 2022, Volume and Issue: 19(2), P. 388 - 400

Published: April 25, 2022

Age-related macular degeneration (AMD) is the leading cause of visual impairment in aging population with limited understanding its pathogenesis and a lack effective treatment. The progression AMD initially characterized by atrophic alterations retinal pigment epithelium, as well formation lysosomal lipofuscin extracellular drusen deposits. Damage caused chronic oxidative stress, protein aggregation inflammatory processes may lead to geographic atrophy and/or choroidal neovascularization fibrosis. role macroautophagy/autophagy pathology steadily emerging. This review describes selective secretory autophagy their biogenesis, senescence-associated phenotype, inflammation epithelial-mesenchymal transition AMD.

Language: Английский

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Oxidative Stress and 4-hydroxy-2-nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-related Diseases

Journal of Immunology Research, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 12

Published: March 23, 2022

Oxidative stress plays an important role in the development of aging-related diseases by accelerating lipid peroxidation polyunsaturated fatty acids cell membrane, resulting production aldehydes, such as malondialdehyde and 4-hydroxy-2-nonenal (4-HNE) other toxic substances. The compound 4-HNE forms adducts with DNA or proteins, disrupting many signaling pathways including regulation apoptosis signal transduction pathways. binding proteins to (4-HNE-protein) acts marker peroxidation, its increasing concentration brain tissues fluids because aging, ultimately gives rise some hallmark disorders, neurodegenerative (Alzheimer’s Parkinson’s diseases), ophthalmic (dry eye, macular degeneration), hearing loss, cancer. This review aims describe physiological origin 4-HNE, elucidate toxicity diseases, discuss detoxifying effect aldehyde dehydrogenase glutathione 4-HNE-driven diseases.

Language: Английский

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Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(3), P. 1296 - 1296

Published: Jan. 28, 2021

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress choroidal vascular dysfunction were suggested be critically involved In this review, we give an overview on the contributing pathophysiology of multifactorial discuss role reactive oxygen species function more detail. Moreover, therapeutic strategies for patients suffering from AMD.

Language: Английский

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Mitochondrial DNA Release in Innate Immune Signaling

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 299 - 332

Published: March 31, 2023

According to the endosymbiotic theory, most of DNA original bacterial endosymbiont has been lost or transferred nucleus, leaving a much smaller (∼16 kb in mammals), circular molecule that is present-day mitochondrial (mtDNA). The ability mtDNA escape mitochondria and integrate into nuclear genome was discovered budding yeast, along with genes regulate this process. Mitochondria have emerged as key regulators innate immunity, it now recognized released cytoplasm, outside cell, circulation activates multiple immune signaling pathways. Here, we first review mechanisms through which including several inducible pores defective mitophagy autophagy. Next, cover how different forms activate specific nucleic acid sensors inflammasomes. Finally, discuss intracellular extracellular release, circulating cell-free promotes systemic inflammation, are implicated human diseases, viral infections, senescence aging.

Language: Английский

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The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 7, 2023

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or resistance as the main cause, and causes damage to various target organs including heart, kidney neurovascular. In terms of pathological physiological mechanisms DM, oxidative stress one leading DM an important link between its complications. Oxidative phenomenon resulting from imbalance production free radicals scavenging antioxidant systems. The site reactive oxygen species (ROS) mitochondria, which are also organelles damaged. high glucose environment, impaired electron transport chain within mitochondria leads ROS, prompts increased proton leakage altered mitochondrial membrane potential (MMP), in turn releases cytochrome c (cyt-c), apoptosis. This subsequently vicious cycle clearance body's system, transcription protein synthesis DNA (mtDNA), responsible for encoding proteins, repair systems, contributing dysfunction. paper reviews dysfunction environment induced model, looks forward providing new treatment plan based on

Language: Английский

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Oxidative Stress and Antioxidants in Age-Related Macular Degeneration

Antioxidants, Journal Year: 2023, Volume and Issue: 12(7), P. 1379 - 1379

Published: July 3, 2023

Oxidative stress plays a crucial role in aging-related eye diseases, including age-related macular degeneration (AMD), cataracts, and glaucoma. With age, antioxidant reparative capacity decreases, excess levels of reactive oxygen species produce oxidative damage many ocular cell types underling pathologies. In AMD, loss central vision the elderly is caused primarily by retinal pigment epithelium (RPE) dysfunction and/or choroidal neovascularization that trigger malfunction photo-sensing photoreceptor cells. Along with various genetic environmental factors contribute to aging have critical involvement AMD pathogenesis. To this end, dietary intake antioxidants proven way scavenge free radicals prevent or slow progression. This review focuses on highlights pathogenic from both clinical experimental studies. The beneficial roles micronutrients are also summarized.

Language: Английский

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