Age-Related Macular Degeneration: The Molecular Link between Oxidative Damage, Tissue-Specific Inflammation and Outer Retinal Disease

2010 ◽  
Vol 51 (3) ◽  
pp. 1276 ◽  
Author(s):  
Joe G. Hollyfield
Keyword(s):  
Oxidative Damage ◽  
Macular Degeneration ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Tissue Specific ◽  
Damage Tissue ◽  
Age Related

scholarly journals A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration

2021 ◽  
Vol 10 (10) ◽  
pp. 2072
Author(s):  
Phoebe Lin ◽  
Scott M. McClintic ◽  
Urooba Nadeem ◽  
Dimitra Skondra
Keyword(s):  
Macular Degeneration ◽  
Intestinal Microbiota ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Intestinal Microbiome ◽  
Age Related ◽  
Intestinal Dysbiosis ◽  
Apo E ◽  
Dry Amd

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.

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 Fully-automated atrophy segmentation in dry age-related macular degeneration in optical coherence tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasmine Derradji ◽  
Agata Mosinska ◽  
Stefanos Apostolopoulos ◽  
Carlos Ciller ◽  
Sandro De Zanet ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Layer ◽  
Optical Coherence ◽  
Age Related ◽  
Layer Segmentation

AbstractAge-related macular degeneration (AMD) is a progressive retinal disease, causing vision loss. A more detailed characterization of its atrophic form became possible thanks to the introduction of Optical Coherence Tomography (OCT). However, manual atrophy quantification in 3D retinal scans is a tedious task and prevents taking full advantage of the accurate retina depiction. In this study we developed a fully automated algorithm segmenting Retinal Pigment Epithelial and Outer Retinal Atrophy (RORA) in dry AMD on macular OCT. 62 SD-OCT scans from eyes with atrophic AMD (57 patients) were collected and split into train and test sets. The training set was used to develop a Convolutional Neural Network (CNN). The performance of the algorithm was established by cross validation and comparison to the test set with ground-truth annotated by two graders. Additionally, the effect of using retinal layer segmentation during training was investigated. The algorithm achieved mean Dice scores of 0.881 and 0.844, sensitivity of 0.850 and 0.915 and precision of 0.928 and 0.799 in comparison with Expert 1 and Expert 2, respectively. Using retinal layer segmentation improved the model performance. The proposed model identified RORA with performance matching human experts. It has a potential to rapidly identify atrophy with high consistency.

scholarly journals Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaushal Sharma ◽  
Priya Battu ◽  
Ramandeep Singh ◽  
Suresh Kumar Sharma ◽  
Akshay Anand
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Clinical Images ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd ◽  
Group 1

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.

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 Microbiota and age-related macular degeneration: where are we today?

ABOUTOPEN ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 23-28
Author(s):  
Angelo Maria Minnella ◽  
Francesca Albanesi ◽  
Martina Maceroni
Keyword(s):  
Macular Degeneration ◽  
Clinical Course ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Low Grade ◽  
Leaky Gut ◽  
Proinflammatory Mediators ◽  
Age Related ◽  
Simple Sugar ◽  
Low Grade Inflammation

Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. It is well known that age, family history, smoking, nutrition, and inflammation contribute to the development of AMD. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

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.

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