The role of oxidative stress in the pathogenesis of ocular diseases: an overview

Molecular Biology Reports, Год журнала: 2024, Номер 51(1)

Опубликована: Март 27, 2024

Язык: Английский

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AIBP: A New Safeguard against Glaucomatous Neuroinflammation

Cells, Год журнала: 2024, Номер 13(2), С. 198 - 198

Опубликована: Янв. 21, 2024

Glaucoma is a group of ocular diseases that cause irreversible blindness. It characterized by multifactorial degeneration the optic nerve axons and retinal ganglion cells (RGCs), resulting in loss vision. Major components glaucoma pathogenesis include glia-driven neuroinflammation impairment mitochondrial dynamics bioenergetics, leading to neurodegeneration. In this review article, we summarize current evidence for emerging role apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory neuroprotective factor retina. Due its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from plasma membrane inflammatory activated cells. This results reduced expression TLR4-associated, cholesterol-rich lipid rafts inhibition downstream signaling. Intracellular localized mitochondria modulates mitophagy through ubiquitination mitofusins 1 2. Importantly, elevated intraocular pressure induces deficiency mouse models human glaucomatous leads activation TLR4 Müller glia, triggering dysfunction both RGCs compromising visual function model. Conversely, restoring retina reduces neuroinflammation, prevents death, protects function. These provide new insight into mechanism suggest therapeutic potential treatment glaucoma.

Язык: Английский

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Ferroptosis in Glaucoma: A Promising Avenue for Therapy

Advanced Biology, Год журнала: 2024, Номер 8(5)

Опубликована: Фев. 27, 2024

Abstract Glaucoma, a blind‐leading disease largely since chronic pathological intraocular high pressure (ph‐IOP). Hitherto, it is reckoned incurable for irreversible neural damage and challenges in managing IOP. Thus, significant to develop neuroprotective strategies. Ferroptosis, initially identified as an iron‐dependent regulated death that triggers Fenton reactions culminates lipid peroxidation (LPO), has emerged focal point multiple tumors neurodegenerative diseases. Researches show iron homeostasis play critical roles the optic nerve (ON) retinal ganglion cells (RGCs), suggesting targeted treatments could be effective. In glaucoma, apart from lesions, disrupted metal balance increased oxidative stress trabecular meshwork (TM) are observed. These disturbances lead extracellular matrix excretion disorders, known sclerotic mechanisms, resulting refractory blockages. Importantly, stress, downstream effect of ferroptosis, also key factor cell senescence. It plays crucial role both etiology risk glaucoma. Moreover, ferroptosis induces non‐infectious inflammation, which exacerbate glaucomatous injury. Therefore, relevance glaucoma extensive multifaceted. this review, study delves into current understanding mechanisms aiming provide clues inform clinical therapeutic practices.

Язык: Английский

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Mitochondrial dysfunction in glaucomatous degeneration

International Journal of Ophthalmology, Год журнала: 2023, Номер 16(5), С. 811 - 823

Опубликована: Апрель 28, 2023

Glaucoma is a kind of optic neuropathy mainly manifested in the permanent death retinal ganglion cells (RGCs), atrophy nerve, and loss visual ability. The main risk factors for glaucoma consist pathological elevation intraocular pressure (IOP) aging. Although mechanism remains an open question, theory related to mitochondrial dysfunction has been emerging last decade. Reactive oxygen species (ROS) from respiratory chain are abnormally produced as result dysfunction. Oxidative stress takes place when cellular antioxidant system fails remove excessive ROS promptly. Meanwhile, more studies show that there other common features glaucoma, including damage DNA (mtDNA), defective quality control, ATP reduction, changes, which worth summarizing further exploring. purpose this review explore glaucomatous neuropathy. Based on mechanism, existing therapeutic options summarized, medications, gene therapy, red-light promising provide feasible neuroprotective ideas treatment glaucoma.

Язык: Английский

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Aging Effects on Optic Nerve Neurodegeneration

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2573 - 2573

Опубликована: Янв. 29, 2023

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding mechanisms of changes can facilitate targeted treatments that arise at any point in life. In this review, we examine these age-related, neurodegenerative nerve, contextualize from anatomic molecular level, and appreciate their relationship with pathophysiology. From simple structural mechanical nerve head (ONH), epigenetic biochemical alterations tissue environment, multiple age-dependent drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, lowered regenerative ability respective axons. conjunction, aging decreases myelin preserve maximal conductivity, even “successfully” regenerated Glial cells, however, regeneratively overcompensate result a microenvironment promotes RGC axonal death. Better elucidating neurodegeneration remains interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, astrocytes; clarifying exact processes aged connective ultrastructural impacts; developing novel technologies pharmacotherapies target known genetic, biochemical, matrisome, neuroinflammatory markers. Management models should account when addressing glaucoma, diabetic retinopathy, other blinding diseases.

Язык: Английский

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Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation

Molecular Aspects of Medicine, Год журнала: 2024, Номер 96, С. 101238 - 101238

Опубликована: Янв. 11, 2024

Язык: Английский

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Microglial cGAS–STING signaling underlies glaucoma pathogenesis

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(36)

Опубликована: Авг. 27, 2024

Characterized by progressive degeneration of retinal ganglion cells (RGCs) and vision loss, glaucoma is the primary cause irreversible blindness, incurable affecting over 78 million patients. However, pathogenic mechanisms leading to glaucoma-induced RGC loss are incompletely understood. Unexpectedly, we found that cGAS-STING (2'3'-cyclic GMP-AMP-stimulator interferon genes) signaling, which surveils displaced double-stranded DNA (dsDNA) in cytosol initiates innate immune responses, was robustly activated during microglia distinct murine models. Global or microglial deletion STING markedly relieved symptoms protected while mice bearing genetic supersensitivity aggravated neuroinflammation loss. Mechanistically, dsDNA from tissue injury causing deleterious macroglia reactivity retinas cytokine-mediated microglia-macroglia interactions, progressively driving apoptotic death RGCs. Remarkably, preclinical investigations targeting signaling intraocular injection TBK1i anti-IFNAR1 antibody prevented losses RGCs vision. Therefore, unravel an essential role underlying pathogenesis suggest promising therapeutic strategies for treating this devastating disease.

Язык: Английский

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Optic nerve diseases and regeneration: How far are we from the promised land?

Clinical and Experimental Ophthalmology, Год журнала: 2023, Номер 51(6), С. 627 - 641

Опубликована: Июнь 15, 2023

Abstract The retinal ganglion cells (RGCs) are the sole output neurons that connect information from retina to brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss axon damage, lead partial or total of vision, which is an irreversible process in mammals. accurate diagnoses crucial for timely treatments prevent irrevocable RGCs loss. After severe ON damage neuropathies, promoting regeneration vital restoring vision. Clearance neuronal debris, decreased intrinsic growth capacity, presence inhibitory factors have been shown contribute failure post‐traumatic CNS regeneration. Here, we review current understanding manifestations various common neuropathies. We also summarise known mechanisms survival mammals, including specific signalling pathways, key transcription factors, reprogramming genes, inflammation‐related stem cell therapy, combination therapies. Significant differences subtypes regenerative capacity after injury found. Finally, highlight developmental states non‐mammalian species capable regenerating axons injury, cellular state neural repair.

Язык: Английский

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Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment

Pharmaceuticals, Год журнала: 2023, Номер 16(9), С. 1193 - 1193

Опубликована: Авг. 22, 2023

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping the optic disc, and typical pattern visual field defects, is leading cause severe impairment blindness worldwide. Elevated intraocular pressure (IOP) risk factor for glaucoma development. However, can also develop at normal levels. An increased susceptibility cells to IOP, systemic vascular dysregulation, endothelial dysfunction, autoimmune imbalances have been suggested as playing role in pathophysiology normal-tension glaucoma. Since inflammation oxidative stress play all forms glaucoma, goal this review article present an overview inflammatory pro-oxidant mechanisms discuss immunomodulatory antioxidant treatment approaches.

Язык: Английский

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Therapeutic effects of tetrahedral framework nucleic acids and tFNAs‐miR22 on retinal ischemia/reperfusion injury

Cell Proliferation, Год журнала: 2024, Номер 57(11)

Опубликована: Июль 31, 2024

Abstract Retinal ischemia/reperfusion injury (RI/R) is a common pathological process in ophthalmic diseases, which can cause severe visual impairment. The mechanisms underlying RI/R damage and repair are still unclear. Scholars actively exploring effective intervention strategies to restore impaired function. With the development of nucleic acid nanomaterials, tetrahedral framework acids (tFNAs) have shown promising therapeutic potential various fields such as stem cells, biosensors, tumour treatment due their excellent biological properties. Besides, miRNA‐22‐3p (miR‐22), an important regulatory factor neural tissue, has been proven positive effects neurodegenerative diseases. By stably constructing complex miR22 (tFNAs‐miR22), we observed that tFNAs‐miR22 had effect on retinal tissue. Previous studies tFNAs effectively deliver miR‐22 into damaged neurons, subsequently exerting neuroprotective effects. Interestingly, found there was certain synergistic between miR‐22. selectively activated ERK1/2 signalling pathway reduce neuronal apoptosis, accelerate cell proliferation, synaptic functional activity. In this study, established simple yet small molecule drug for may become neuroprotectant treating type vision impairment disease future.

Язык: Английский

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