Quercetin-3-O-α-l-arabinopyranoside protects against retinal cell death via blue light-induced damage in human RPE cells and Balb-c mice

2018 ◽  
Vol 9 (4) ◽  
pp. 2171-2183 ◽  
Author(s):  
Jun Kim ◽  
Hong Lan Jin ◽  
Dae Sik Jang ◽  
Kwang Won Jeong ◽  
Se-Young Choung
Keyword(s):  
Cell Death ◽  
Macular Degeneration ◽  
Blue Light ◽  
Visual Loss ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Age-related macular degeneration (AMD) is a chronic degenerative disease that can lead to visual loss and blindness in the elderly.

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 Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

2020 ◽  
Vol 21 (19) ◽  
pp. 7279 ◽  
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Wai Ching Lam ◽  
Amy Cheuk Yin Lo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Severe Visual Loss ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD’s role as a therapeutic new target for future AMD treatment.

scholarly journals NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jiangyuan Gao ◽  
Ruozhou Tom Liu ◽  
Sijia Cao ◽  
Jing Z. Cui ◽  
Aikun Wang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factors ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

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 Nanoceria Particles Are an Eligible Candidate to Prevent Age-Related Macular Degeneration by Inhibiting Retinal Pigment Epithelium Cell Death and Autophagy Alterations

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1617 ◽  
Author(s):  
Annamaria Tisi ◽  
Vincenzo Flati ◽  
Simona Delle Monache ◽  
Luca Lozzi ◽  
Maurizio Passacantando ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Cellular Damage ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Age Related

Retinal pigment epithelium (RPE) dysfunction and degeneration underlie the development of age-related macular degeneration (AMD), which is the leading cause of blindness worldwide. In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs or nanoceria), which are anti-oxidant agents with auto-regenerative properties, are able to preserve the RPE. On ARPE-19 cells, we found that CeO2-NPs promoted cell viability against H2O2–induced cellular damage. For the in vivo studies, we used a rat model of acute light damage (LD), which mimics many features of AMD. CeO2-NPs intravitreally injected three days before LD prevented RPE cell death and degeneration and nanoceria labelled with fluorescein were found localized in the cytoplasm of RPE cells. CeO2-NPs inhibited epithelial-mesenchymal transition of RPE cells and modulated autophagy by the down-regulation of LC3B-II and p62. Moreover, the treatment inhibited nuclear localization of LC3B. Taken together, our study demonstrates that CeO2-NPs represent an eligible candidate to counteract RPE degeneration and, therefore, a powerful therapy for AMD.

scholarly journals The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis

2018 ◽  
Vol 19 (11) ◽  
pp. 3363 ◽  
Author(s):  
Gian Tosi ◽  
Maurizio Orlandini ◽  
Federico Galvagni
Keyword(s):  
Macular Degeneration ◽  
Visual Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Transforming Growth Factors ◽  
Severe Visual Loss ◽  
Age Related ◽  
Experimental Approaches

The multifunctional transforming growth factors-beta (TGF-βs) have been extensively studied regarding their role in the pathogenesis of neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Despite this, their effect remains somewhat controversial. Indeed, both pro- and antiangiogenic activities have been suggested for TGF-β signaling in the development and progression of nAMD, and opposite therapies have been proposed targeting the inhibition or activation of the TGF-β pathway. The present article summarizes the current literature linking TGF-β and nAMD, and reviews experimental data supporting both pro- and antiangiogenic hypotheses, taking into account the limitations of the experimental approaches.

scholarly journals A widespread decrease of chromatin accessibility in age-related macular degeneration

2018 ◽  
Author(s):  
Jie Wang ◽  
Cristina Zibetti ◽  
Peng Shang ◽  
Srinivasa R. Sripathi ◽  
Pingwu Zhang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Advanced Disease ◽  
The Elderly ◽  
Chromatin Accessibility ◽  
Age Related Macular Degeneration ◽  
Epigenetic Changes ◽  
Altered Expression ◽  
Rpe Cells ◽  
Age Related ◽  
Pigmented Epithelium

AbstractAge-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profiled chromatin accessibility in the retina and retinal pigmented epithelium (RPE) from AMD patients and controls. Global decreases in chromatin accessibility occurr in RPE in early AMD, and in the retina with advanced disease, suggesting that dysfunction in RPE cells drives disease progression. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates epigenomic changes seen in AMD, providing an epigenetic link between the known risk factors for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the reduction in chromatin accessibility, identifying potential new targets for treatment of AMD.

scholarly journals Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shigeru Honda ◽  
Yasuo Yanagi ◽  
Hideki Koizumi ◽  
Yirong Chen ◽  
Satoru Tanaka ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Productivity Loss ◽  
Work Productivity ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Resource Utilisation ◽  
Total Work ◽  
Healthcare Resource Utilisation ◽  
Age Related

AbstractThe chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009–2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

Sign in / Sign up

Export Citation Format

Share Document