Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD)

2016 ◽  
Vol 254 (12) ◽  
pp. 2469-2476 ◽  
Author(s):  
Zhaojiang Du ◽  
Xuemei Wu ◽  
Meixia Song ◽  
Peng Li ◽  
Li Wang
Keyword(s):  
Oxidative Damage ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Macrophage Aggregation

scholarly journals Oxidative damage–induced inflammation initiates age-related macular degeneration

2008 ◽  
Vol 14 (2) ◽  
pp. 194-198 ◽  
Author(s):  
Joe G Hollyfield ◽  
Vera L Bonilha ◽  
Mary E Rayborn ◽  
Xiaoping Yang ◽  
Karen G Shadrach ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Pathogenesis in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 173-177
Keyword(s):  
Oxidative Damage ◽  
Macular Degeneration ◽  
Chronic Inflammation ◽  
Choroidal Neovascularization ◽  
Complement System ◽  
Molecular Targets ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Age Related ◽  
The Complement System

The understanding of the pathogenesis of the development of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) continues to evolve. Epidemiological, histopathological, and biochemical evidence indicates that neovascular AMD is associated with oxidative damage, lipofuscin accumulation, chronic inflammation, and mutation in the complement system. Molecular targets have been identified that serve as the basis for developing new, better treatments for neovascular AMD.

scholarly journals Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration

2009 ◽  
Vol 297 (5) ◽  
pp. C1200-C1210 ◽  
Author(s):  
Kurt M. Bertram ◽  
Carolyn J. Baglole ◽  
Richard P. Phipps ◽  
Richard T. Libby
Keyword(s):  
Cell Death ◽  
Oxidative Damage ◽  
Macular Degeneration ◽  
Cell Size ◽  
Cigarette Smoke ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Cigarette smoke is the most important environmental risk factor for developing age-related macular degeneration (AMD). Damage to the retinal pigment epithelium (RPE) caused by cigarette smoke may underlie the etiology of AMD. This study investigated the molecular and cellular effects of cigarette smoke exposure on human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The effect of this exposure on key aspects of RPE vitality including viability, cell size, mitochondrial membrane potential (ΔΨm), superoxide production, 4-hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ caused oxidative damage and apoptosis, characterized by a reduction in cell size and nuclear condensation. Evidence of oxidative damage also included increased lipid peroxidation (4-HNE) and mitochondrial superoxide production, as well as a decrease in intracellular glutathione (GSH). Exogenous administration of antioxidants (GSH and N-acetyl-cysteine) prevented oxidative damage to the RPE cells caused by CSE. Cigarette smoke also induced expression of VEGF, HO-1, and the transcription factor nuclear factor erythroid-derived 2, like 2 (NRF2). However, NRF2 was only modestly involved in CSE-induced HO-1 expression, as shown by the NRF2 small interfering RNA studies. These new findings demonstrate that cigarette smoke is a potent inducer of oxidative damage and cell death in human RPE cells. These data support the hypothesis that cigarette smoke contributes to AMD pathogenesis by causing oxidative damage and cell death to RPE cells.

scholarly journals Autophagy in Age-Related Macular Degeneration: A Regulatory Mechanism of Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zi-Yuan Zhang ◽  
Xiao-Li Bao ◽  
Yun-Yi Cong ◽  
Bin Fan ◽  
Guang-Yu Li
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Cell Degeneration ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss and irreversible blindness in the elderly population worldwide. Retinal pigment epithelial (RPE) cells are the major site of pathological alterations in AMD. They are responsible for the phagocytosis of shed photoreceptor outer segments (POSs) and clearance of cellular waste under physiological conditions. Age-related, cumulative oxidative stimuli contribute to the pathogenesis of AMD. Excessive oxidative stress induces RPE cell degeneration and incomplete digestion of POSs, leading to the continuous accumulation of cellular waste (such as lipofuscin). Autophagy is a major system of degradation of damaged or unnecessary proteins. However, degenerative RPE cells in AMD patients cannot perform autophagy sufficiently to resist oxidative damage. Increasing evidence supports the idea that enhancing the autophagic process can properly alleviate oxidative injury in AMD and protect RPE and photoreceptor cells from degeneration and death, although overactivated autophagy may lead to cell death at early stages of retinal degenerative diseases. The crosstalk among the NFE2L2, PGC-1, p62, AMPK, and PI3K/Akt/mTOR pathways may play a crucial role in improving disturbed autophagy and mitigating the progression of AMD. In this review, we discuss how autophagy prevents oxidative damage in AMD, summarize potential neuroprotective strategies for therapeutic interventions, and provide an overview of these neuroprotective mechanisms.

scholarly journals T Cells and Macrophages Responding to Oxidative Damage Cooperate in Pathogenesis of a Mouse Model of Age-Related Macular Degeneration

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88201 ◽  
Author(s):  
Fernando Cruz-Guilloty ◽  
Ali M. Saeed ◽  
Stephanie Duffort ◽  
Marisol Cano ◽  
Katayoon B. Ebrahimi ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Model ◽  
Oxidative Damage ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals N-Acetyl-L-cysteine Protects Human Retinal Pigment Epithelial Cells from Oxidative Damage: Implications for Age-Related Macular Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Marcia R. Terluk ◽  
Mara C. Ebeling ◽  
Cody R. Fisher ◽  
Rebecca J. Kapphahn ◽  
Ching Yuan ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Atp Depletion ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Ros Production ◽  
Age Related

Age-related macular degeneration (AMD) involves the loss of retinal pigment epithelium (RPE) and photoreceptors and is one of the leading causes of blindness in the elderly. Oxidative damage to proteins, lipids, and DNA has been associated with RPE dysfunction and AMD. In this study, we evaluated oxidative stress in AMD and the efficacy of antioxidant, N-acetyl-L-cysteine (NAC), in protecting RPE from oxidative damage. To test this idea, primary cultures of RPE from human donors with AMD (n=32) or without AMD (No AMD, n=21) were examined for expression of NADPH oxidase (NOX) genes, a source of reactive oxygen species (ROS). Additionally, the cells were pretreated with NAC for 2 hours and then treated with either hydrogen peroxide (H2O2) or tert-butyl hydroperoxide (t-BHP) to induce cellular oxidation. Twenty-four hours after treatment, ROS production, cell survival, the content of glutathione (GSH) and adenosine triphosphate (ATP), and cellular bioenergetics were measured. We found increased expression of p22phox, a NOX regulator, in AMD cells compared to No AMD cells (p=0.02). In both AMD and No AMD cells, NAC pretreatment reduced t-BHP-induced ROS production and protected from H2O2-induced cell death and ATP depletion. In the absence of oxidation, NAC treatment improved mitochondrial function in both groups (p<0.01). Conversely, the protective response exhibited by NAC was disease-dependent for some parameters. In the absence of oxidation, NAC significantly reduced ROS production (p<0.001) and increased GSH content (p=0.02) only in RPE from AMD donors. Additionally, NAC-mediated protection from H2O2-induced GSH depletion (p=0.04) and mitochondrial dysfunction (p<0.05) was more pronounced in AMD cells compared with No AMD cells. These results demonstrate the therapeutic benefit of NAC by mitigating oxidative damage in RPE. Additionally, the favorable outcomes observed for AMD RPE support NAC’s relevance and the potential therapeutic value in treating AMD.

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