The Role of Extra-cellular Matrix in Age-related Macular Degeneration
The Role of Extra-cellular Matrix in Age-related Macular Degeneration

Author: Ngai Hang Victor Chong

Publisher:

Published: 2010

Total Pages: 328

ISBN-13:

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There is increasing evidence to suggest that changes in the extracellular matrix (ECM) play an important role in the pathogenesis of age-related macular degeneration (AMD). These changes in ECM in AMD may be an exaggeration of the ECM alterations seen in aging. Similarly, AMD shares many clinical and pathological features with Sorsby's Fundus Dystrophy (SFD), an autosomal dominant disease associated with mutations in the gene for TIMP-3, a tissue inhibitor of metalloproteinases (MMPs), an important regulator of ECM. -- In an attempt to understand the role of ECM in AMD, this research initially focused on the expression of TIMP-3 in the Bruch's membrane in aging, SFD and AMD and its spatial correlation with ECM proteins and Bruch's membrane thickness. We found TIMP-3 are accumulated in Bruch's membrane in all three conditions and correlated well with the distribution of elastin and collagen VI tetramer. -- We developed an in vitro system to assess whether the expression of TIMPs and MMPs can be modified by cytokines and to determine whether deposits under the retinal pigment epithelium (RPE) could be modulated by the change of expression. Sub-RPE deposits developed in vitro shared similar ultrastructural changes to those seen in AMD and these deposits were modulated with retinal homogenate, TNF-a and MMP-2 providing proof of principle that RPE deposits can be formed and modified in vitro. -- We then studied the thickness and integrity of the elastic layer of the Bruch's membrane within the eye in both normal and AMD donors. The elastic layer has poor integrity in areas prone to have choroidal neovascularisation, a hallmark of neovascular AMD. This is more so in the case of AMD donors suggesting that the elastic layer may be a vital physical barrier for the invasion of these abnormal choroidal blood vessels.

The Role of Extracellular Matrix Proteins in Retinal Development and Disease
The Role of Extracellular Matrix Proteins in Retinal Development and Disease

Author: Erin Tolhurst Dunkle

Publisher:

Published: 2006

Total Pages: 252

ISBN-13:

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The retina is a multilayered, complex tissue that provides the basis for vision. The cells of the neural retina are heavily influenced by the surrounding extracellular matrix (ECM), and this influence is crucial to proper development and maintenance needed for sight. In this study, the functions of two ECM proteins were investigated.

The Role of Matrix Metalloproteinase in Human Body Pathologies
The Role of Matrix Metalloproteinase in Human Body Pathologies

Author: Francesco Travascio

Publisher: BoD – Books on Demand

Published: 2017-12-20

Total Pages: 202

ISBN-13: 9535137174

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Matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes involved in physiological as well as in pathological processes in the human organism. MMPs play a key role in the remodeling of the extracellular matrix. Such a process may occur because of tissue homeostasis, morphogenesis, and tissue repair. However, remodeling could also be a part of many pathological states such as arthritis, cardiovascular diseases, neurodegenerative diseases, or impaired development in congenital anomalies. This book overviews the role of MMPs in different pathologies affecting the human body.

Influence of Matrix Metalloproteinases MMP-2, -3 and on Age- Related Macular Degeneration Development
Influence of Matrix Metalloproteinases MMP-2, -3 and on Age- Related Macular Degeneration Development

Author: Rasa Liutkeviciene

Publisher:

Published: 2017

Total Pages:

ISBN-13:

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Age-related macular degeneration (AMD) is the leading cause of significant and irreversible central visual loss as it affects a small area of the retina, called the macula. However, the pathogenesis of still fairly understood. AMD has a multifactorial etiology, and its development might be influenced by body peculiarities, environmental and genetic factors. Risk factors such as age, gender, cigarette smoking, colour of iris, nutrition, body mass index, oxidative stress, and genetic factors (complement factor H gene, Apo E gene, matrix metalloproteinases (MMPs) genes and others) increase probability to develop AMD. Here, we discuss about choroidal neovascularization process, where hypoxia, inflammatory process, and proteolytic enzymes play a main role, but mainly we focus on the family of matrix metalloproteinases (MMPs), especially on MMP -2, -3 and -9, and their impact on AMD development. MMPs belong to a family of proteolytic zinc-containing enzymes, and their mechanism under normal physiological conditions is precisely regulated, but when is dysregulated, MMPs become a cause of various diseases, including and AMD. MMPs are capable of degrading most of the extracellular matrix components, which are important in the remodeling during angiogenesis. Angiogenesis is the main pathological process associated with age-related macular degeneration development. Activated endothelial cells release MMPs which by degrading the basilar membrane allows capillaries to grow beneath the retina and retinal layers. Such capillaries often bleed, more liquids are filtered through the walls, and fibrous tissue grows within. Furthermore, swelling of the retina and impaired vision occur. In this book chapter, we focus on AMD prevalence, risk factors, clinics, diagnostics and influence of MMP-2, -3 and -9 on AMD development.

Focus on Eye Research
Focus on Eye Research

Author: O. R. Ioseliani

Publisher: Nova Publishers

Published: 2005

Total Pages: 252

ISBN-13: 9781594544347

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The consequences of ageing populations combined with the strain to the human eye caused by computers and widespread poor nutritional practices has resulted in an upsurge of research dealing with vision. This new book presents leading-edge research in this field.

Age-related Macular Degeneration
Age-related Macular Degeneration

Author: D. Virgil Alfaro

Publisher: Lippincott Williams & Wilkins

Published: 2006

Total Pages: 396

ISBN-13: 0781738997

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A renowned group of retina surgeons presents promising new developments in age-related macular degeneration, with emphasis on the most significant advances in the past five years. Content addresses all aspects of management, including anatomy, physiology, and pathophysiology; imaging of the macula in age-related macular degeneration; prevention measures and treatment; treatment; and future directions. Abundantly illustrated and superbly organized, this book serves as an excellent reference and textbook.

Macular Dystrophies
Macular Dystrophies

Author: Giuseppe Querques

Publisher: Springer

Published: 2016-02-15

Total Pages: 128

ISBN-13: 3319266217

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​This book provides the ophthalmologist with the most recently available data on the macular dystrophies, a group of many different inherited or sporadic eye conditions linked by a problem with photoreceptors or other structures of the central retina. Internationally recognized experts in the field present the latest evidence and discuss their own personal experiences with regard to each of the principal dystrophies as well as some very rare entities. Topics covered include molecular biology, state-of-the-art diagnostic techniques, and the newest treatment options, including still experimental therapies. Attention is also devoted to a range of issues that continue to be debated. The editors have taken care to ensure that chapters are of a uniformly high standard while not sacrificing the originality of the individual authors. Macular Dystrophies will fully acquaint the reader with both the latest research findings and the current and emerging approaches to diagnosis and treatment.

Investigating Age-related Macular Degeneration
Investigating Age-related Macular Degeneration

Author: Jennifer C. Tournear

Publisher:

Published: 2018

Total Pages: 238

ISBN-13: 9780438392229

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Age-related macular degeneration (AMD) is a retinal disease that can cause severe vision loss. It is responsible for the majority of blindness in developed countries in the elderly population. The disease is characteristically multifactorial where oxidative stress, inflammation and retinal lipofuscin (cellular waste product) accumulation have been indicated in disease progression. The retinal pigment epithelial (RPE) attaches to the Bruch's membrane (BM) and the symbiotic relationship between these two layers of the retina is essential for the visual cycle to function normally. Retinal lipofuscin is believed to contribute to drusen (characteristic deposits in the AMD BM) that negatively impact the BM and, in turn, the retina. Investigating the biological changes to the retina that are catalyzed by chemical reactions, such as photooxidation, can help to further the understanding of AMD. It is believed that when the BM is significantly modified, the RPE cells detach and undergo cell death. Retinal cell death is a hallmark of AMD. This work includes the investigation of ARPE-19 cell death when extracellular matrix (ECM) has been modified to model AMD through oxidative stress, aging and inflammation. Results indicate overlapping cell death pathways are activated as a result of ECM modification including proinflammatory cell death mechanisms: pyroptosis and necroptosis. Lipofuscin extracts obtained from human donor eyes where donors were previously diagnosed with one of three retinal diseases (wet AMD, dry AMD or diabetic retinopathy) are investigated using liquid chromatography mass spectrometry. Photooxidation products, inflammatory biomarkers and aging biomarkers are investigated as being components making up lipofuscin. Specifically, the observation of these components in association with a particular retinal disease is examined. Results indicate trends associated with oxidative stress markers being linked to wet AMD samples and inflammatory biomarkers being mostly associated with dry AMD samples. This work uses a two-prong approach to explore AMD onset and progression. Through the investigation of cell death using disease models and the components of lipofuscin buildup in human tissue, we begin to identify the impact and consequences these biological changes have on the retina.

The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration
The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration

Author: Emina Colak

Publisher:

Published: 2018

Total Pages: 0

ISBN-13:

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Age-related macular degeneration (AMD) is a complex, degenerative and progressive chronic disease that leads to severe visual loss. The prevalence of early AMD accounts for 18% in the population between 65 and 74 years of age and even 30% in subjects older than 74 years. The articles published in the last decade point out to a significant role of oxidative stress in the onset and development of age-related macular degeneration. Generally, reactive oxygen species (ROS) are produced in the eye during light absorption and physiological metabolic processes. The level of oxidative stress is kept under control by the action of antioxidants and reparative enzymes. Excessive synthesis of ROS leads to increased oxidative modification of lipids, proteins and DNA, causing oxidative damage of cytoplasmic and nuclear cell elements and changes of the extracellular matrix. The accumulation of oxidatively modified compounds in drusen deposits will initiate the onset and development of AMD. The objective of this review was to highlight the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.