Progress of autophagy in the pathogenesis of dry age-related macular degeneration

2021 ◽  
Vol 2 (4) ◽  
pp. 233-236
Author(s):  
Wen Gao ◽  
Keyword(s):  
Macular Degeneration ◽  
Signaling Pathway ◽  
Age Related Macular Degeneration ◽  
Research Progress ◽  
Related Factor ◽  
Age Related ◽  
Nrf2 Signaling Pathway ◽  
Wide Range ◽  
Mutual Regulation ◽  
New Perspective

Age-related macular degeneration (AMD) is a major clinical blind-inducing eye disease, and its pathogenesis is closely related to the autophagy of RPE cells and the signaling pathway of nuclear factor erythroid-2 related factor 2 (Nrf2). Autophagy is one of the common and important physiological phenomena in human body, which is of vital significance for maintaining the stability and metabolism of cells. Nrf2 is a key transcription factor regulating cells to fight against foreign bodies and oxidative damage, and Nrf2 signaling pathway plays a wide range of cell protective functions in anti-tumor, anti-stress and other aspects. With the development of research, it is found that there are extensive interaction mechanisms between autophagy and Nrf2 signaling pathway. Inhibition of autophagy leads to accumulation of p62, which activates the Nrf2 signaling pathway by binding with Keap1 (kelch-like ech-associated protein1). At the same time, studies have also found that reactive oxygen species (ROS) and other factors also participate in the mutual regulation between autophagy and Nrf2.This paper will review the recent research progress on the interaction between Nrf2 signaling pathway and autophagy in the development of AMD. Hope to provide a new perspective for the treatment of AMD.

scholarly journals Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 622
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Hanna Heloterä ◽  
Stephen Marry ◽  
Ali Koskela ◽  
Juha M. T. Hyttinen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Complement Component ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Complement Factor ◽  
Age Related ◽  
Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

scholarly journals Central Role of Oxidative Stress in Age-Related Macular Degeneration: Evidence from a Review of the Molecular Mechanisms and Animal Models

2020 ◽  
Vol 2020 ◽  
pp. 1-19 ◽  
Author(s):  
Samuel Abokyi ◽  
Chi-Ho To ◽  
Tim T. Lam ◽  
Dennis Y. Tse
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Vascular Endothelial ◽  
Age Related ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.

TSP1 ameliorates age-related macular degeneration by regulating the STAT3-iNOS signaling pathway

2020 ◽  
Vol 388 (1) ◽  
pp. 111811 ◽  
Author(s):  
Jing Li ◽  
Jiaqi He ◽  
Xiang Zhang ◽  
Jiakai Li ◽  
Peiquan Zhao ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Signaling Pathway ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Herbal Treatments for Age-Related Macular Degeneration: A Literature Review

2020 ◽  
pp. 01-13
Keyword(s):  
Risk Factors ◽  
Medicinal Plants ◽  
Literature Review ◽  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Carnosic Acid ◽  
Retinal Diseases ◽  
Lycium Barbarum ◽  
Age Related ◽  
Wide Range

Background and aim: Age-related macular degeneration (AMD) is one of the major causes of blindness and it has risk factors such as obesity, hypertension, smoking, or genetic characteristics. There is no certain cure for AMD till now, so it is very important to design new therapeutic agents or strategies for treatment of AMD. This literature review assessed the effects of different plants or herbal extracts on the retinal diseases such as AMD either for treatment or prevention of disease. Materials and methods: Fifteen studies were included in this literature review and assessed possible herbal treatments or preventions of AMD or its related diseases and risk factors. Results: From a wide range of medicinal plants, Artemisia annua contained artemisinin, Lycium barbarum, Fructus barbarum rich in carotenoids like zeaxanthin, Scutellaria baicalensis contained wogonin, saffron, rosemary contained carnosic acid, and Melissa officinalis are of the most important and beneficial medicinal plants that can be used for production and design of new drugs and therapeutics for AMD. They act via different mechanisms such as anti-oxidation, anti-VEGF, or anti-inflammatory actions. There are several other important herbal effective compounds for AMD, such as fisetin and luteolin that are polyphenols. Also, there are other herbal compounds such as HESA-A, Traditional Chinese Medicine (TCM), Guibi-tang (GBT), Samul-tang (SMT), and Sipjeondaebo-tang (SDT) that are contained in several different beneficial medicinal plants and their extracts for AMD. Conclusion: There is a need for more investigations on these medicinal plants and their benefits on AMD, but they can be beneficial in lowering the risk of AMD or several other retinal diseases and prevention of them. For each mechanism included in AMD pathogenesis, one or more medicinal plant is introduced in this review.

scholarly journals Frequent hypomorphic alleles account for a significant fraction of ABCA4 disease and distinguish it from age-related macular degeneration

2017 ◽  
Vol 54 (6) ◽  
pp. 404-412 ◽  
Author(s):  
Jana Zernant ◽  
Winston Lee ◽  
Frederick T Collison ◽  
Gerald A Fishman ◽  
Yuri V Sergeev ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Late Onset ◽  
Direct Sequencing ◽  
Age Related Macular Degeneration ◽  
Imaging Data ◽  
Reading Frame ◽  
Complex Disorders ◽  
Age Related ◽  
Wide Range ◽  
Biallelic Mutations

BackgroundVariation in theABCA4gene is causal for, or associated with, a wide range of phenotypes from early onset Mendelian retinal dystrophies to late-onset complex disorders such as age-related macular degeneration (AMD). Despite substantial progress in determining the causal genetic variation, even complete sequencing of the entire open reading frame and splice sites ofABCA4identifies biallelic mutations in only 60%–70% of cases; 20%–25% remain with one mutation and no mutations are found in 10%–15% of cases with clinically confirmed ABCA4 disease. This study was designed to identify missing causal variants specifically in monoallelic cases of ABCA4 disease.MethodsDirect sequencing and analysis were performed in a large familial ABCA4 disease cohort of predominately European descent (n=643). Patient phenotypes were assessed from clinical and retinal imaging data.ResultsWe determined that a hypomorphicABCA4variant c.5603A>T (p.Asn1868Ile), previously considered benign due to high minor allele frequency (MAF) (~7%) in the general population, accounts for 10% of the disease, >50% of the missing causal alleles in monoallelic cases, ~80% of late-onset cases and distinguishes ABCA4 disease from AMD. It results in a distinct clinical phenotype characterised by late-onset of symptoms (4th decade) and foveal sparing (85%). Intragenic modifying effects involving this variant and another, c.2588G>C (p.Gly863Ala) allele, were also identified.ConclusionsThese findings substantiate the causality of frequent missense variants and their phenotypic outcomes as a significant contribution to ABCA4 disease, particularly the late-onset phenotype, and its clinical variation. They also suggest a significant revision of diagnostic screening and assessment ofABCA4variation in aetiology of retinal diseases.

scholarly journals A new perspective on lipid research in age-related macular degeneration

2018 ◽  
Vol 67 ◽  
pp. 56-86 ◽  
Author(s):  
Elisabeth M. van Leeuwen ◽  
Eszter Emri ◽  
Benedicte M.J. Merle ◽  
Johanna M. Colijn ◽  
Eveline Kersten ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Lipid Research ◽  
Age Related ◽  
New Perspective
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