CURRENT KNOWLEDGE AND TRENDS IN AGE-RELATED MACULAR DEGENERATION

Retina ◽  
2013 ◽  
Vol 33 (8) ◽  
pp. 1487-1502 ◽  
Author(s):  
Raul Velez-Montoya ◽  
Scott C. N. Oliver ◽  
Jeffrey L. Olson ◽  
Stuart L. Fine ◽  
Naresh Mandava ◽  
...  
2019 ◽  
Vol 20 (9) ◽  
pp. 903-918 ◽  
Author(s):  
Francesca Liva ◽  
Doretta Cuffaro ◽  
Elisa Nuti ◽  
Susanna Nencetti ◽  
Elisabetta Orlandini ◽  
...  

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.


2020 ◽  
Vol 245 (17) ◽  
pp. 1615-1625 ◽  
Author(s):  
Tanu Parmar ◽  
Joseph T Ortega ◽  
Beata Jastrzebska

Progressive retinal degeneration manifesting as age-related macular degeneration (AMD) in the elderly affects millions of individuals worldwide. Among various blinding diseases, AMD is the leading cause of central vision impairment in developed countries. Poor understanding of AMD etiology hampers the development of therapeutics against this devastating ocular disease. Currently, daily intravitreal injections of anti-angiogenic drugs, preventing abnormal vessel growth are the only treatment option for wet AMD. However, for dry AMD associated with retinal atrophy, at present there is no cure available. Recent clinical research has demonstrated beneficial effects of plant-derived compounds for various eye disorders. Thus, the ongoing efforts toward discovering efficient treatments preventing or delaying AMD progression focus on implementing a healthy diet rich in vitamins, including vitamin A, E, and C, minerals and carotenoids, in particular lutein and zeaxanthin, to reduce the disease burden. In addition, studies in cell culture and animal models indicated therapeutic potential of dietary polyphenolic compounds present in fruits and vegetables. These natural compounds protect visual function and retinal morphology likely due to their anti-oxidant and anti-inflammatory properties. Although understanding of the exact mechanism of these compounds’ positive effects requires further investigation, they provide non-invasive alternative to battle AMD-like condition. Additionally, studies carried in animal models mimicking AMD-like pathology, examining the pharmacological potential of particular retinoid analogs, demonstrated promising results for their use, and thus they should be considered as an option in developing therapies for AMD. In here, we summarize the most current knowledge regarding developments of therapeutic options to maintain ocular health and prevent vision loss associated with aging. Impact statement Age-related macular degeneration (AMD) is a devastating retinal degenerative disease. Epidemiological reports showed an expected increasing prevalence of AMD in the near future. The only one existing FDA-approved pharmacological treatment involves an anti-vascular endothelial growth factor (VEGF) therapy with serious disadvantages. This limitation emphasizes an alarming need to develop new therapeutic approaches to prevent and treat AMD. In this review, we summarize scientific data unraveling the therapeutic potential of the specific retinoid and natural compounds. The experimental results reported by us and other research groups demonstrated that retinoid analogs and compounds with natural product scaffolds could serve as lead compounds for the development of new therapeutic agents with potential to prevent or slow down the pathogenesis of AMD.


2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach

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.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1217 ◽  
Author(s):  
C. Henrique Alves ◽  
Rosa Fernandes ◽  
Ana Raquel Santiago ◽  
António Francisco Ambrósio

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Carlos A. Moreira-Neto ◽  
Eric M. Moult ◽  
James G. Fujimoto ◽  
Nadia K. Waheed ◽  
Daniela Ferrara

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.


2019 ◽  
Vol 13 (1) ◽  
pp. 90-99
Author(s):  
Nasim Salimiaghdam ◽  
Mohammad Riazi-Esfahani ◽  
Paula S. Fukuhara ◽  
Kevin Schneider ◽  
M. Cristina Kenney

Age-related Macular Degeneration (AMD) is a type of maculopathy that results in irreversible visual impairment among the aged population in developed countries. The early stages of AMD can be diagnosed by the presence of drusen beneath the retinal pigment epithelial (RPE) cells. The advanced stages of AMD are geographical atrophy (dry type) and neovascular AMD (wet type), which lead to progressive and severe vision loss. The advanced stage of dry AMD can be identified by extensive large drusen, detachment of the RPE layer and finally degeneration of photoreceptors leading to central vision loss. The late stage of wet AMD is diagnosed by the presence of Choroidal Neovascularization (CNV) identified by Optical Coherence Tomography (OCT) or retinal angiography. The principal of AMD management is to impede the progression of early AMD to advanced levels. Patients with CNV are treated with anti-VEGF (Vascular Endothelial Growth Factor) compounds to inhibit blood vessel growth and thereby reducing vision loss. Although preventive methods for dry AMD are under investigation, there are no proven effective treatments. A variety of environmental and genetic related risk factors are associated with increased incidence and progression of AMD. The genetic factors are found in the complement, angiogenic and lipid pathways. However, environmental factors, such as smoking and nutrition, are also major risk factors. Smoking is a modifiable environmental risk factor, which greatly increases the incidence and progress of AMD compared to non-smokers. There is growing evidence for the positive influence of a healthy diet containing high levels of anti-oxidant supplements. The reduction of serum lipids is another effective strategy for prevention AMD. Although no single preventive approach has been identified, knowing the high risk factors of AMD, along with modification of lifestyle is important for this multifactorial disease, especially in populations with higher genetic susceptibility. Though recent progress in early diagnosis of the disease has facilitated early and efficient intervention, further studies are required to gain more clarification of specific pathophysiology. In spite of decades of focused research on AMD, the pathogenesis of AMD is still not completely understood. Recently, numerous novel methods, including imaging techniques, new drug delivery routes, and therapeutic strategies, are improving the management of AMD. In this review, we discuss the current knowledge related to epidemiology and classifications of AMD.


Retina ◽  
2014 ◽  
Vol 34 (3) ◽  
pp. 423-441 ◽  
Author(s):  
Raul Velez-Montoya ◽  
Scott C. N. Oliver ◽  
Jeffrey L. Olson ◽  
Stuart L. Fine ◽  
Hugo Quiroz-Mercado ◽  
...  

2001 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ursula Körner-Stiefbold

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.


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