scholarly journals Age-related Macular Degeneration: Current Knowledge of Zinc Metalloproteinases Involvement

2019 ◽  
Vol 20 (9) ◽  
pp. 903-918 ◽  
Author(s):  
Francesca Liva ◽  
Doretta Cuffaro ◽  
Elisa Nuti ◽  
Susanna Nencetti ◽  
Elisabetta Orlandini ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Age Related ◽  
A Disintegrin And Metalloproteinase

Background: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced Retinal Pigment Epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular matrix (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue Inhibitors of Metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development. Objective: This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed. Conclusion: This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMP inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.

Tractional Maculopathies in Age-related Macular Degeneration

2012 ◽  
Vol 05 (02) ◽  
pp. 119 ◽  
Author(s):  
Cynthia X Qian ◽  
William J Foster ◽  
Flavio A Rezende ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
The Past ◽  
Age Related ◽  
Surgical Options ◽  
Made In

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Much progress has been and continues to be made in search of better visual outcomes for dry and exudative AMD. Over the past decade, the importance of vitreomacular attachments has been recognized in AMD. In this article, we better characterize and describe vitreomacular and photoreceptor-retinal pigment epithelium interface relationships in AMD among treated and untreated patients and describe the surgical options available as well as their outcomes and possible complications.

scholarly journals The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Complex Structure ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Strong Connection ◽  
Age Related

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

scholarly journals Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1217 ◽  
Author(s):  
C. Henrique Alves ◽  
Rosa Fernandes ◽  
Ana Raquel Santiago ◽  
António Francisco Ambrósio
Keyword(s):  
Macular Degeneration ◽  
Vascular System ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Microglial Cells ◽  
Endothelial Cell Proliferation ◽  
Metabolic Demand ◽  
Age Related

The retina is a highly metabolically active tissue with high-level consumption of nutrients and oxygen. This high metabolic demand requires a properly developed and maintained vascular system. The retina is nourished by two systems: the central retinal artery that supplies the inner retina and the choriocapillaris that supplies the outer retina and retinal pigment epithelium (RPE). Pathological neovascularization, characterized by endothelial cell proliferation and new vessel formation, is a common hallmark in several retinal degenerative diseases, including age-related macular degeneration (AMD). A limited number of studies have suggested that microglia, the resident immune cells of the retina, have an important role not only in the pathology but also in the formation and physiology of the retinal vascular system. Here, we review the current knowledge on microglial interaction with the retinal vascular system under physiological and pathological conditions. To do so, we first highlight the role of microglial cells in the formation and maintenance of the retinal vasculature system. Thereafter, we discuss the molecular signaling mechanisms through which microglial cells contribute to the alterations in retinal and choroidal vasculatures and to the neovascularization in AMD.

scholarly journals Choriocapillaris Loss in Advanced Age-Related Macular Degeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Carlos A. Moreira-Neto ◽  
Eric M. Moult ◽  
James G. Fujimoto ◽  
Nadia K. Waheed ◽  
Daniela Ferrara
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Tissue Loss ◽  
Age Related

The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy. Others have hypothesized that deposition of complement complexes on and around the choriocapillaris could be related to the tissue loss observed in early AMD. The development of imaging modalities, such as optical coherence tomography angiography (OCTA), have led to a better understanding of underlying physiopathological mechanisms in AMD. OCTA showed atrophy of choriocapillaris underneath and beyond the region of photoreceptors and RPE loss, in agreement with previous histopathologic studies. The evolution of OCTA technology suggests that CNV seems to originate from regions of severe choriocapillaris alteration. Significant progress has been made in the understanding of development and progression of GA and CNV. In vivo investigation of the choriocapillaris using OCTA may lead to new insights related to underlying disease mechanisms in AMD.

scholarly journals NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Jiangyuan Gao ◽  
Ruozhou Tom Liu ◽  
Sijia Cao ◽  
Jing Z. Cui ◽  
Aikun Wang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factors ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE) and Bruch’s membrane (BM) in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA) or choroidal neovascularization (CNV). As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

scholarly journals Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Janusz Blasiak ◽  
Goran Petrovski ◽  
Zoltán Veréb ◽  
Andrea Facskó ◽  
Kai Kaarniranta
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Rich

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

scholarly journals Cellular senescence in the aging retina and developments of senotherapies for age-related macular degeneration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keng Siang Lee ◽  
Shuxiao Lin ◽  
David A. Copland ◽  
Andrew D. Dick ◽  
Jian Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Cellular Senescence ◽  
Vision Loss ◽  
Inflammatory Responses ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Age Related

AbstractAge-related macular degeneration (AMD), a degenerative disease in the central macula area of the neuroretina and the supporting retinal pigment epithelium, is the most common cause of vision loss in the elderly. Although advances have been made, treatment to prevent the progressive degeneration is lacking. Besides the association of innate immune pathway genes with AMD susceptibility, environmental stress- and cellular senescence-induced alterations in pathways such as metabolic functions and inflammatory responses are also implicated in the pathophysiology of AMD. Cellular senescence is an adaptive cell process in response to noxious stimuli in both mitotic and postmitotic cells, activated by tumor suppressor proteins and prosecuted via an inflammatory secretome. In addition to physiological roles in embryogenesis and tissue regeneration, cellular senescence is augmented with age and contributes to a variety of age-related chronic conditions. Accumulation of senescent cells accompanied by an impairment in the immune-mediated elimination mechanisms results in increased frequency of senescent cells, termed “chronic” senescence. Age-associated senescent cells exhibit abnormal metabolism, increased generation of reactive oxygen species, and a heightened senescence-associated secretory phenotype that nurture a proinflammatory milieu detrimental to neighboring cells. Senescent changes in various retinal and choroidal tissue cells including the retinal pigment epithelium, microglia, neurons, and endothelial cells, contemporaneous with systemic immune aging in both innate and adaptive cells, have emerged as important contributors to the onset and development of AMD. The repertoire of senotherapeutic strategies such as senolytics, senomorphics, cell cycle regulation, and restoring cell homeostasis targeted both at tissue and systemic levels is expanding with the potential to treat a spectrum of age-related diseases, including AMD.

scholarly journals Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration

2022 ◽  
Vol 15 (1) ◽  
pp. 62
Author(s):  
Mara C. Ebeling ◽  
Zhaohui Geng ◽  
Madilyn R. Stahl ◽  
Rebecca J. Kapphahn ◽  
Heidi Roehrich ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Mitochondrial Function ◽  
Drug Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Induced Pluripotent

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.

scholarly journals Tractional Maculopathies in Age-related Macular Degeneration

2012 ◽  
Vol 06 (05) ◽  
pp. 300
Author(s):  
Cynthia X Qian ◽  
William J Foster ◽  
Flavio A Rezende ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
The Past ◽  
Age Related ◽  
Surgical Options ◽  
Made In

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Much progress has been and continues to be made in search of better visual outcomes for dry and exudative AMD. Over the past decade, the importance of vitreomacular attachments has been recognised in AMD. In this article, the authors better characterise and describe vitreomacular and photoreceptor-retinal pigment epithelium interface relationships in AMD among treated and untreated patients and describe the surgical options available as well as their outcomes and possible complications.

scholarly journals Age-related Macular Degeneration: Simple Review

2021 ◽  
pp. 35-40
Author(s):  
Abdulaziz Saeed A. Alghamdi ◽  
Abeer Ahmed Al Mutairi ◽  
Afaf Mahal R. Alanazi ◽  
Asrar Awad M. Almutairi ◽  
Mei Khalid S. Alfaqiri ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Significant Loss ◽  
Age Related Macular Degeneration ◽  
Molecular Dissection ◽  
Age Related ◽  
Race Ethnicity

Age-related macular degeneration (AMD) is a common, chronic, and innovative degenerative disease of the macula that affects the elderly, with significant loss of imagination and foresight due to abnormalities within the photoreceptor, retinal pigment epithelium, Bruch's membrane, and the choroidal complex. AMD is currently being elucidated through molecular dissection of histopathological samples and genetic coupling. Threat factors for AMD can be broadly based on character elements (e.g. age, gender, race / ethnicity, heredity, and socioeconomic reputation) and environmental factors (e.g. consumption and alcohol consumption). Signs and signs of AMD are: Druids. This is one of the early symptoms and symptoms of AMD and the presence of neovascularization in the macula in humid conditions. Form of AMD A medical examination is usually sufficient for the installation of an AMD analysis, but the use of additional examinations such as fundus vehicle fluorescence, optical coherence tomography, fluorescein angiography and inexperienced angiography with indocyanine for diffuse macular anomalies makes sense. unimaginative and prophetic cure cases can help.

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