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Survey of Ophthalmology 1987The clinical and histopathological features of age-related macular degeneration (AMD) include a relationship with age, and the presence of pigmentary disturbances,... (Review)
Review
The clinical and histopathological features of age-related macular degeneration (AMD) include a relationship with age, and the presence of pigmentary disturbances, drusen, thickening of Bruch's membrane, and basal laminar deposits. AMD is an advanced stage of a deteriorative process that takes place in all eyes. The primary lesion in AMD appears to reside in the retinal pigment epithelium (RPE), possibly resulting from its high rate of molecular degradation. Beginning early in life, and continuing throughout the life span, cells of the RPE gradually accumulate sacs of molecular debris. These residual bodies (lipofuscin) are remnants of the incomplete degradation of abnormal molecules which have been damaged within the RPE cells or derived from phagocytized rod and cone membranes. Progressive engorgement of RPE cells with these functionless residues is associated with the extrusion of aberrant materials which accumulate in Bruch's membrane and aggregate in the form of drusen and basal laminar deposits. These excretions contribute to the further deterioration of the RPE. Loss of vision results from death of visual cells due to degeneration of RPE cells, or the effects of leakage from neovascular membranes that invade the region of abnormal extracellular deposits.
Topics: Aging; Atrophy; Basement Membrane; Choroid; Humans; Macular Degeneration; Pigment Epithelium of Eye; Pigmentation Disorders
PubMed: 3299827
DOI: 10.1016/0039-6257(87)90115-9 -
The Medical Letter on Drugs and... Mar 2022
Topics: Antibodies, Monoclonal; Diabetes Mellitus; Diabetic Retinopathy; Humans; Macular Degeneration; Macular Edema
PubMed: 35294428
DOI: No ID Found -
Current Molecular Medicine 2019Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina... (Review)
Review
Age-related macular degeneration (AMD) is an eye disorder affecting predominantly the older people above the age of 50 years in which the macular region of the retina deteriorates, resulting in the loss of central vision. The key factors associated with the pathogenesis of AMD are age, smoking, dietary, and genetic risk factors. There are few associated and plausible genes involved in AMD pathogenesis. Common genetic variants (with a minor allele frequency of >5% in the population) near the complement genes explain 40-60% of the heritability of AMD. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Genetic changes in and around several complement system genes, including the CFH, contribute to the formation of drusen and progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are normally involved in tissue remodeling also play a critical role in the pathogenesis of AMD. MMPs are involved in the degradation of cell debris and lipid deposits beneath retina but with age their functions get affected and result in the drusen formation, succeeding to macular degeneration. In this review, AMD pathology, existing knowledge about the normal and pathological role of complement system proteins and MMPs in the eye is reviewed. The scattered data of complement system proteins, MMPs, drusenogenesis, and lipofusogenesis have been gathered and discussed in detail. This might add new dimensions to the understanding of molecular mechanisms of AMD pathophysiology and might help in finding new therapeutic options for AMD.
Topics: Animals; Complement System Proteins; Humans; Macular Degeneration; Matrix Metalloproteinases
PubMed: 31456517
DOI: 10.2174/1566524019666190828150625 -
Ophthalmology. Retina Oct 2022
Topics: Humans; Macular Degeneration; Retinal Drusen
PubMed: 35598859
DOI: 10.1016/j.oret.2022.05.014 -
Arizona Medicine Feb 1978
Topics: Humans; Macular Degeneration; Retinal Degeneration
PubMed: 626607
DOI: No ID Found -
Molecular Vision Nov 1999Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility... (Review)
Review
Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.
Topics: Apolipoproteins E; Environmental Exposure; Genetic Predisposition to Disease; Humans; Macular Degeneration; Retinal Drusen; Twin Studies as Topic
PubMed: 10562653
DOI: No ID Found -
Therapeutische Umschau. Revue... Mar 2009Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises... (Review)
Review
Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).
Topics: Adult; Age Factors; Aged; Antioxidants; Aptamers, Nucleotide; Diet; Fluorescein Angiography; Fundus Oculi; Genetic Predisposition to Disease; Humans; Macular Degeneration; Middle Aged; Photochemotherapy; Polymorphism, Genetic; Prevalence; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Smoking; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Zinc
PubMed: 19266466
DOI: 10.1024/0040-5930.66.3.189 -
Molecular Interventions Oct 2010Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as... (Review)
Review
Age-related macular degeneration (AMD) is the most common cause of visual impairment among the elderly in developed countries, and its prevalence is thus increasing as the population ages; however, treatment options remain limited because the etiology and pathogenesis of AMD are incompletely defined. Recently, much progress has been made in gene discovery and mechanistic studies, which clearly indicate that AMD involves the interaction of multiple genetic and environmental factors. The identification of genes that have a substantial impact on the risk for AMD is not only facilitating the diagnosis and screening of populations at risk but is also elucidating key molecular pathways of pathogenesis. Pharmacogenetic studies of treatment responsiveness among patients with the "wet" form of AMD are increasingly proving to be clinically relevant; pharmacogenetic approaches hold great promise for both identifying patients with the best chance for vision recovery as well as tailoring individualized therapies.
Topics: Genetic Predisposition to Disease; Humans; Macular Degeneration; Risk Factors
PubMed: 21045241
DOI: 10.1124/mi.10.5.4 -
European Journal of Pharmaceutics and... Sep 2015Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop... (Review)
Review
Age-related macular degeneration (AMD) is a progressive disease of the central retina and the main cause of legal blindness in industrialized countries. Risk to develop the disease is conferred by both individual as well as genetic factors with the latter being increasingly deciphered over the last decade. Therapeutically, striking advances have been made for the treatment of the neovascular form of late stage AMD while for the late stage atrophic form of the disease, which accounts for almost half of the visually impaired, there is currently no effective therapy on the market. This review highlights our current knowledge on the genetic architecture of early and late stage AMD and explores its potential for the discovery of novel, target-guided treatment options. We reflect on current clinical and experimental therapies for all forms of AMD and specifically note a persisting lack of efficacy for treatment in atrophic AMD. We further explore the current insight in AMD-associated genes and pathways and critically question whether this knowledge is suited to design novel treatment options. Specifically, we point out that known genetic factors associated with AMD govern the risk to develop disease and thus may not play a role in its severity or progression. Treatments based on such knowledge appear appropriate rather for prevention than treatment of manifest disease. As a consequence, future research in AMD needs to be greatly focused on approaches relevant to the patients and their medical needs.
Topics: Animals; Disease Progression; Drug Design; Genetic Predisposition to Disease; Humans; Macular Degeneration; Molecular Targeted Therapy; Risk; Severity of Illness Index
PubMed: 25986585
DOI: 10.1016/j.ejpb.2015.04.039 -
Reviews in the Neurosciences Apr 2024Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been... (Review)
Review
Age-related macular degeneration (AMD) is a complex, multifactorial disease leading to progressive and irreversible retinal degeneration, whose pathogenesis has not been fully elucidated yet. Due to the complexity and to the multiple features of the disease, many efforts have been made to develop animal models which faithfully reproduce the overall AMD hallmarks or that are able to mimic the different AMD stages. In this context, light damage (LD) rodent models of AMD represent a suitable and reliable approach to mimic the different AMD forms (dry, wet and geographic atrophy) while maintaining the time-dependent progression of the disease. In this review, we comprehensively reported how the LD paradigms reproduce the main features of human AMD. We discuss the capability of these models to broaden the knowledge in AMD research, with a focus on the mechanisms and the molecular hallmarks underlying the pathogenesis of the disease. We also critically revise the remaining challenges and future directions for the use of LD models.
Topics: Animals; Humans; Macular Degeneration
PubMed: 38153807
DOI: 10.1515/revneuro-2023-0130