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Current Opinion in Pharmacology Apr 2022Age-related macular degeneration (AMD) is a progressive retinal disease that is a leading cause of visual impairment and severe vision loss. The number of people... (Review)
Review
Age-related macular degeneration (AMD) is a progressive retinal disease that is a leading cause of visual impairment and severe vision loss. The number of people affected by AMD is increasing and constitutes a huge worldwide health problem. The beneficial effects of fish consumption on AMD have been revealed over the past decades, and in this review, we summarizes the beneficial effects of fatty fish on AMD and its mechanism of action. Fatty fish affects the development of AMD by inhibiting neovascularization, interacting with retinal pigment epithelial (RPE) cells, displacing Omega-6, and inducing cellular responses. It is recommended that people at high risk or with moderate or more severe AMD should consider eating more fatty fish in addition to maintaining a healthy lifestyle of weight control and smoking cessation and the need to promote new models of personalized AMD prevention and treatment.
Topics: Animals; Humans; Macular Degeneration
PubMed: 35217394
DOI: 10.1016/j.coph.2022.102186 -
Seminars in Immunopathology Jan 2018Complement turnover is tightly regulated throughout the human body in order to prevent over-activation and subsequent damage from inflammation. In the eye, low-level... (Review)
Review
Complement turnover is tightly regulated throughout the human body in order to prevent over-activation and subsequent damage from inflammation. In the eye, low-level complement activation is maintained to provide immune tolerance in this immune privileged organ. Conversely, the complement system is suppressed in the cornea to protect it from continuous immunological insult. Over-activation of the complement cascade has been implicated in the disease progression of glaucoma and diabetic retinopathy and is now known to be a central driver in the pathogenesis of age-related macular degeneration (AMD). Indeed, it is with AMD where the most recent and exciting work has been carried out with complement-based therapies entering into clinical trials. However, the success of these trials will depend upon delivering the therapeutics to the correct anatomical sites within the eye, so a full understanding of how complement regulation is compartmentalized in the eye is required, a topic that will be highlighted in this review.
Topics: Animals; Clinical Trials as Topic; Complement Activation; Complement System Proteins; Disease Susceptibility; Eye Diseases; Humans; Macular Degeneration; Molecular Targeted Therapy; Treatment Outcome
PubMed: 28948331
DOI: 10.1007/s00281-017-0649-6 -
Clinical Genetics Aug 2013Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and... (Review)
Review
Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients.
Topics: Biomarkers; Disease Progression; Humans; Macular Degeneration; Pharmacogenetics; Prognosis; Risk Factors
PubMed: 23713713
DOI: 10.1111/cge.12206 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim: Analyze the ophthalmic studies on diagnostics and treatment of patients with age-related macular degeneration to optimize diagnostics and management tactics.
OBJECTIVE
The aim: Analyze the ophthalmic studies on diagnostics and treatment of patients with age-related macular degeneration to optimize diagnostics and management tactics.
PATIENTS AND METHODS
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.
CONCLUSION
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.
Topics: Antioxidants; Humans; Macular Degeneration; Middle Aged; Vitamin D; Vitamins
PubMed: 33843651
DOI: No ID Found -
CMAJ : Canadian Medical Association... Jul 2021
Review
Topics: Humans; Macular Degeneration; Pentosan Sulfuric Polyester
PubMed: 34312174
DOI: 10.1503/cmaj.201900-f -
Disease Models & Mechanisms May 2015Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is... (Review)
Review
Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.
Topics: Animals; Humans; Macular Degeneration; Models, Biological; Stem Cell Transplantation
PubMed: 26035859
DOI: 10.1242/dmm.017236 -
Experimental Biology and Medicine... Dec 2018Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An... (Review)
Review
Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An objective method for functional assessment of photoreceptor physiology can benefit early detection and better treatment evaluation of AMD and other eye diseases that are known to cause photoreceptor dysfunctions. This article summarizes in vitro study of IOS mechanisms and in vivo demonstration of IOS imaging of intact animals. Further development of the functional IOS imaging may provide a revolutionary solution to achieve objective assessment of human photoreceptors.
Topics: Animals; Humans; Macular Degeneration; Photoreceptor Cells, Vertebrate; Tomography, Optical Coherence
PubMed: 30482040
DOI: 10.1177/1535370218816517 -
Clinical Chemistry and Laboratory... May 2017Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers... (Review)
Review
Advanced age-related macular degeneration (AAMD) is a complex sight-threating disease of public health significance. Micro RNAs (miRNAs) have been proposed as biomarkers for AAMD. The presence of certain single nucleotide polymorphisms (SNPs) may influence the explanatory value of these biomarkers. Here we present findings from an integrated approach used to determine whether AAMD-associated SNPs have the capacity to influence miRNA-mRNA pairing and, if so, to what extent such pairing may be manifested in a discrete AAMD transcriptome. Using a panel of 8854 SNPs associated with AAMD at p-values ≤5.0E-7 from a cohort of >30,000 elderly people, we identified SNPs in miRNA target-encoding constituents of: (1) regulator of complement activation (RCA) genes (rs390679, CFHR1, p≤2.14E-214 | rs12140421, CFHR3, p≤4.63E-29); (2) genes of major histocompatibility complex (MHC) loci (rs4151672, CFB, p≤8.91E-41 | rs115404146, HLA-C, p≤6.32E-12 | rs1055821, HLA-B, p≤1.93E-9 | rs1063355, HLA-DQB1, p≤6.82E-14); and (3) genes of the 10q26 AAMD locus (rs1045216, PLEKHA1, p≤4.17E-142 | rs2672603, ARMS2, p≤7.14E-46). We used these findings with existing data on AAMD-related retinal miRNA and transcript profiles for the purpose of making inferences on SNP-mRNA-miRNA-AAMD relationships. Four of 12 miRNAs significantly elevated in AAMD retina (hsa-miR-155-5p, hsa-let-7a-5p, hsa-let-7b-5p hsa-let-7d-5p) also showed strong pairing capacity (TarBase 7.1 context++ score <-0.2, miRanda 3.3 pairing score >150) with miRNA target transcripts encoded by AAMD-associated SNPs resident in HLA-DQB1 (rs1063355, hsa-miR-155-5p) and TGFBR1 (rs868, hsa-let-7). Three of the 12 miRNAs overexpressed in AAMD retina are inducible by NFkB and have high affinity targets in the complement factor H (CFH) mRNA 3' UTR. We used ENSEMBL to identify polymorphic regions in the CFH mRNA 3' UTR with the capacity to disrupt miRNA-mRNA pairing. Two variants (rs766666504 and rs459598) existed in DNA sequence encoding the seed region of hsa-miR-146a-5p in the CFH mRNA 3' UTR - as this miRNA is also elevated in both vitreous and serum of people with AAMD, it shows great value as a biomarker. Our findings suggest that knowledge on the nature of DNA sequence variation may increase the explanatory power of miRNA biomarkers in genetically diverse populations, while yielding information with which to develop: (1) mechanistic tests on processes implicated in AMD pathogenesis; and, (2) site-specific small molecules (synthetic mimetics or anti-miRNAs) with preventive or therapeutic efficacy for AAMD.
Topics: Gene Expression Regulation; Humans; Macular Degeneration; MicroRNAs; Polymorphism, Single Nucleotide; Retina; Vitreous Body
PubMed: 28343170
DOI: 10.1515/cclm-2016-0898 -
International Journal of Molecular... Aug 2020Age-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is... (Review)
Review
Age-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch's membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990-2020, using the following keywords: AMD, extracellular matrix, Bruch's membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention.
Topics: Animals; Humans; Macular Degeneration; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Neuroprotective Agents; Polymorphism, Genetic
PubMed: 32824762
DOI: 10.3390/ijms21165934 -
Molecular Vision Jan 2014Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for... (Review)
Review
Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate vascular maturation, rather than its arrest or destruction. This would neutralize hypoxia, thus removing the stimulus that drives neovascularization and in turn the need for repeated lifelong intravitreal therapy. A pro-angiogenic approach would eliminate neovascular leakage and ultimately complete repair and preserve the neurosensory retina.
Topics: Angiogenesis Inhibitors; Choroidal Neovascularization; Humans; Macular Degeneration
PubMed: 24426775
DOI: No ID Found