scholarly journals Modern view on the etiopathogenesis of age-related macular degeneration and the role of molecular genetic determinants in it

2021 ◽  
Vol 9 (3) ◽  
pp. 21-27
Author(s):  
N.V. Malachkova ◽  
Mohammad Mashhour Mohammad Masa’deh ◽  
Osama Mohammad Miteb Al-Jarrah ◽  
H.P. Liudkevych ◽  
D.S. Sukhan
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
High Specificity ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Age Related

Age-related macular degeneration mainly affects the elderly and is one of the most common causes of rapidly progressive vision loss. Over more than 150 years of research, the scientific community has gone from understanding the macroscopic picture of the lesion, presumable identification of drusen as the main morphological manifestation of nosology, to detailed classifications and determine the role of genetic determinants in the etiopathogenesis of the disease — high specificity, the possibility of preventive analysis, and much unclear in the field of genetic diagnosis of eye diseases determine the accurate attention of specialized research groups to the early diagnosis using genetic analysis. The review article was aimed to systematize the information about possible links in the pathogenesis of age-related macular degeneration and identify potential polymorphisms that can initiate and modulate the activity of these links. During the study, we could find out five main mechanisms of damage to the vascular membrane of the eye itself, which are affected by single nucleotide polymorphisms. The hig­hest affinity was shown by genetic variants of separate sites of CFH (rs1061170), HTRA1 (rs11200638), TNF (rs1800629), VEGFA (rs2010963). Literature data obtained from foreign and national sources indexed by Scopus, Web of Science databases, in particular for the last 5 years, pay special attention to these areas as potential predictors or modifiers of pathological processes involved in the process of macular degeneration. Despite the large number of studies examining the predisposition, pathogenesis, diagnosis, and treatment of age-related macular degeneration to stop the spread of vision loss, only a few issues are understood thoroughly. Considering the successful cases of application of biological and gene therapy for the management of such patients, we see new horizons in the detailed study of molecular interactions that underlie the pathology. The review confirms the active role of polymorphisms in one of the most relevant pathological processes of the human eye.

scholarly journals Intravitreal Ranibizumab Treatment and Treatment Regimens in Wet-Form (Neovascular) Age-Related Macular Degeneration

2017 ◽  
pp. 189-197
Keyword(s):  
Macular Degeneration ◽  
Progressive Disease ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Therapeutic Tool ◽  
Intravitreal Ranibizumab ◽  
Treatment Regimens ◽  
Age Related ◽  
Ranibizumab Treatment

Age-related macular degeneration (AMD) is a chronic and progressive disease of the central retina that causes vision loss in people over 50 years of age. With an understanding of the role of VEGF in AMD, intravitreal anti-VEGF agents are used as the most important therapeutic tool in the management of AMD. In this review we try to discuss intravitreal ranibizumab treatment and treatment regimens in wet (neovascular) age-related macular degeneration.

scholarly journals Mechanism of Inflammation in Age-Related Macular Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Francesco Parmeggiani ◽  
Mario R. Romano ◽  
Ciro Costagliola ◽  
Francesco Semeraro ◽  
Carlo Incorvaia ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Microglial Activation ◽  
Vision Loss ◽  
Dietary Habits ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Oxidized Lipoproteins ◽  
Severe Vision Loss

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

scholarly journals AGE-RELATED MACULAR DEGENERATION – CURRENT STATE OF THE PROBLEM AND PROPHYLAXIS METHODS

2021 ◽  
Vol 74 (3) ◽  
pp. 767-772
Author(s):  
Tetiana M. Komarova ◽  
Oksana P. Vitovska ◽  
Julia I. Komisarenko ◽  
Vita M. Kohan
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Current State ◽  
Central Vision Loss ◽  
Age Related ◽  
Inappropriate Treatment ◽  
Scientific Papers ◽  
Chronic Progressive Disease

The aim: Analyze the ophthalmic studies on diagnostics and treatment of patients with age-related macular degeneration to optimize diagnostics and management tactics. Materials and methods: The analysis of scientific papers due to age-related macular degeneration, vitamin D and its functions from scientometric databases: PubMed, Scopus, Web of Science. The methods were next: systematic approach, analysis, summarization and comparison. Conclusions: Age-related macular degeneration is a chronic, progressive disease among people older than 50 years. Late diagnostics and inappropriate treatment may lead to irreversible central vision loss and social disadaptation. Modern studies on the pathogenesis and treatment of this pathology (that are due to the role of the immune system, antioxidants and microelements) demonstrate the effectiveness and prospects for further development around the world to find new ways to solve this problem.

scholarly journals The role of molecular genetic factors in age-related macular degeneration

2009 ◽  
Vol 72 (4) ◽  
pp. 567-572 ◽  
Author(s):  
Luciana Negrão Frota de Almeida ◽  
Rachel Melilo Carolino ◽  
Diogo Cazelli Sperandio ◽  
Márcio Bittar Nehemy ◽  
LA De Marco
Keyword(s):  
Macular Degeneration ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Chris M. Pappas ◽  
Moussa A. Zouache ◽  
Stacie Matthews ◽  
Caitlin D. Faust ◽  
Jill L. Hageman ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Full Spectrum ◽  
Tagging Snp ◽  
Risk Variants ◽  
Age Related ◽  
Functional Consequences ◽  
Risk Protection

Abstract Background Single-variant associations with age-related macular degeneration (AMD), one of the most prevalent causes of irreversible vision loss worldwide, have been studied extensively. However, because of a lack of refinement of these associations, there remains considerable ambiguity regarding what constitutes genetic risk and/or protection for this disease, and how genetic combinations affect this risk. In this study, we consider the two most common and strongly AMD-associated loci, the CFH-CFHR5 region on chromosome 1q32 (Chr1 locus) and ARMS2/HTRA1 gene on chromosome 10q26  (Chr10 locus). Results By refining associations within the CFH-CFHR5 locus, we show that all genetic protection against the development of AMD in this region is described by the combination of the amino acid-altering variant CFH I62V (rs800292) and genetic deletion of CFHR3/1. Haplotypes based on CFH I62V, a CFHR3/1 deletion tagging SNP and the risk variant CFH Y402H are associated with either risk, protection or neutrality for AMD and capture more than 99% of control- and case-associated chromosomes. We find that genetic combinations of CFH-CFHR5 haplotypes (diplotypes) strongly influence AMD susceptibility and that individuals with risk/protective diplotypes are substantially protected against the development of disease. Finally, we demonstrate that AMD risk in the ARMS2/HTRA1 locus is also mitigated by combinations of CFH-CFHR5 haplotypes, with Chr10 risk variants essentially neutralized by protective CFH-CFHR5 haplotypes. Conclusions Our study highlights the importance of considering protective CFH-CFHR5 haplotypes when assessing genetic susceptibility for AMD. It establishes a framework that describes the full spectrum of AMD susceptibility using an optimal set of single-nucleotide polymorphisms with known functional consequences. It also indicates that protective or preventive complement-directed therapies targeting AMD driven by CFH-CFHR5 risk haplotypes may also be effective when AMD is driven by ARMS2/HTRA1 risk variants.

scholarly journals Genetic risk factors for late age-related macular degeneration in India

2017 ◽  
Vol 102 (9) ◽  
pp. 1213-1217 ◽  
Author(s):  
Anand Rajendran ◽  
Pankaja Dhoble ◽  
Periasamy Sundaresan ◽  
Vijayan Saravanan ◽  
Praveen Vashist ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Population Based ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Limited Data ◽  
Genetic Determinants ◽  
Single Nucleotide ◽  
Age Related ◽  
Disease Study

Background/AimsThere are limited data from India on genetic variants influencing late age-related macular degeneration (AMD). We have previously reported associations from a population-based study in India (the India age-related eye disease study (INDEYE)) of early AMD and single nucleotide polymorphisms (SNPs) in ARMS2/HTRA1 and no association with CFH, C2 or CFB. Late AMD cases were too few for meaningful analyses. We aimed to investigate SNPs for late AMD through case enrichment and extend the loci for early AMD.MethodsFundus images of late AMD hospital cases were independently graded by the modified Wisconsin AMD grading scheme. In total 510 cases with late AMD (14 geographic atrophy and 496 neovascular AMD (nvAMD)), 1876 with early AMD and 1176 with no signs of AMD underwent genotyping for selected SNPs. We investigated genotype and per-allele additive associations (OR and 95% CIs) with nvAMD or early AMD. Bonferroni adjusted P values are presented.ResultsWe found associations with nvAMD for CFHY402H variant (rs1061170) (OR=1.99, 95% CI 1.67 to 2.37, P=10−6), ARMS2 (rs10490924) (OR=2.94, 95% CI 2.45 to 3.52, P=10−9), C2 (rs547154) (OR=0.67, 95% CI 0.53 to 0.85, P=0.01), ABCA1 (rs1883025) (OR=0.77, 95% CI 0.65 to 0.92, P=0.04) and an SNP near VEGFA (rs4711751) (OR=0.64, 95% CI 0.54 to 0.77, P=10−3). We found no associations of TLR3 (rs3775291), CFD (rs3826945), FRK (rs1999930) or LIPC (rs10468017) or APOE ε4 alleles with nvAMD or early AMD, nor between early AMD and rs1883025 or rs4711751.ConclusionsThe major genetic determinants of nvAMD risk in India are similar to those in other ancestries, while findings for early AMD suggest potential differences in the pathophysiology of AMD development.

scholarly journals Genetic Determinants Highlight the Existence of Shared Etiopathogenetic Mechanisms Characterizing Age-Related Macular Degeneration and Neurodegenerative Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Claudia Strafella ◽  
Valerio Caputo ◽  
Andrea Termine ◽  
Carlo Fabrizio ◽  
Paola Ruffo ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Neurodegenerative Disorders ◽  
Reference Group ◽  
Bioinformatic Analysis ◽  
Axonal Guidance ◽  
Age Related Macular Degeneration ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Age Related ◽  
Synergistic Modulation

Age-related macular degeneration (AMD) showed several processes and risk factors in common with neurodegenerative disorders (NDDs). The present work explored the existence of genetic determinants associated with AMD, which may provide insightful clues concerning its relationship with NDDs and their possible application into the clinical practice. In this study, 400 AMD patients were subjected to the genotyping analysis of 120 genetic variants by OpenArray technology. As the reference group, 503 samples representative of the European general population were utilized. Statistical analysis revealed the association of 23 single-nucleotide polymorphisms (SNPs) with AMD risk. The analysis of epistatic effects revealed that ARMS2, IL6, APOE, and IL2RA could contribute to AMD and neurodegenerative processes by synergistic modulation of the expression of disease-relevant genes. In addition, the bioinformatic analysis of the associated miRNA variants highlighted miR-196a, miR-6796, miR-6499, miR-6810, miR-499, and miR-7854 as potential candidates for counteracting AMD and neurodegenerative processes. Finally, this work highlighted the existence of shared disease mechanisms (oxidative stress, immune-inflammatory response, mitochondrial dysfunction, axonal guidance pathway, and synaptogenesis) between AMD and NDDs and described the associated SNPs as candidate biomarkers for developing novel strategies for early diagnosis, monitoring, and treatment of such disorders in a progressive aging population.

scholarly journals Age-Related Macular Degeneration: Pathogenesis, Genetic Background, and the Role of Nutritional Supplements

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Marilita M. Moschos ◽  
Eirini Nitoda ◽  
Irini P. Chatziralli ◽  
Constantinos A. Demopoulos
Keyword(s):  
Macular Degeneration ◽  
Genetic Background ◽  
Vision Loss ◽  
Nutritional Supplements ◽  
Age Related Macular Degeneration ◽  
Light Radiation ◽  
Age Related ◽  
Severe Vision Loss ◽  
And Oxidative Stress

Age-related macular degeneration (ARMD) is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

Gene polymorphisms associated with an increased risk of exudative age-related macular degeneration in a Spanish population

2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Gene Polymorphisms ◽  
Age Related Macular Degeneration ◽  
Spanish Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Exudative Amd ◽  
Age Related ◽  
Increased Risk

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.

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