scholarly journals Case Report: Resolution of submacular haemorrhage secondary to exudative age-related macular degeneration after a single intravitreal dobesilate injection

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 271 ◽  
Author(s):  
Pedro Cuevas ◽  
Luis Antonio Outeiriño ◽  
Carlos Azanza ◽  
Javier Angulo ◽  
Guillermo Giménez-Gallego
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Subretinal Space ◽  
Case Presentation ◽  
Central Vision Loss ◽  
First Case ◽  
Age Related ◽  
Neurosensory Retina

Introduction: Submacular haemorrhage is not an unusual cause of acute central vision loss, particularly in older people. It may be caused by a number of conditions, most common of which is exudative age-related madular degeneration. In patients affected by this type of macular degeneration, choroidal neovascularization extends into the subretinal space, producing substantial bleeding in approximately 17% of cases, resulting in large haemorrhages in the subretinal space that detach the neurosensory retina from the supporting retinal pigment epithelial (RPE) layer. This leads to substantial vision loss because of a relatively fast process of extensive photoreceptor atrophy in the overlying neuroretina and formation of macular scarsCase presentation: We describe a patient with submacular haemorrhage secondary to exudative age-related macular degeneration, treated with intravitreal injection of dobesilate. Two months later, visual acuity in the treated eye reached 0.50 with a significant improvement of the distortion and an anatomical resolution of the haemorrhage, as confirmed by optical coherence tomography.Conclusions: Submacular haemorrhage secondary to exudative age-related macular degeneration can be successfully treated with intravitreal dobesilate. To our knowledge, this is the first case reporting a resolution of submacular haemorrhage after a single dobesilate injection.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

scholarly journals Superoxide Dismutase-1 Induced Oxidative Stress Mediated Apoptosis in Murine Retinal Pigment Epithelial Cells

2019 ◽  
Vol 8 (4S2) ◽  
pp. 463-466
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Superoxide Dismutase 1 ◽  
Central Vision Loss ◽  
Age Related ◽  
Pigment Epithelial Cells

Age related macular degeneration (AMD) is a complicated ocular disease which occurs in elderly people and leads to central vision loss. The AMD generated because of overproduction of oxidative stress which leads to RPE cell death. The present study investigates whether SOD1 induced MRPE cell death based on that overexpression of SOD1 in MRPE cells which induced cell death. The SOD1 gradually increased ROS production and fragmentation of nuclei. To explore the ER stress persuaded UPR via GRP78, and CHOP, protein expression level analyses were carried out by western blotting. Together, our results represent that SOD1 could possibly produce the oxidant induced MRPE cell death.

scholarly journals Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration?

2019 ◽  
Vol 20 (3) ◽  
pp. 762 ◽  
Author(s):  
Thierry Léveillard ◽  
Nancy Philp ◽  
Florian Sennlaub
Keyword(s):  
Macular Degeneration ◽  
Aerobic Glycolysis ◽  
Tricarboxylic Acid Cycle ◽  
Retinal Pigment ◽  
Basolateral Membrane ◽  
Age Related Macular Degeneration ◽  
Subretinal Space ◽  
Outer Retina ◽  
Choroidal Circulation ◽  
Age Related

The retinal pigment epithelium (RPE) forms the outer blood–retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized via OXPHOS. Excess lactate in the RPE is transported across the basolateral membrane to the choroid. The uptake of glucose by cone photoreceptor cells is enhanced by rod-derived cone viability factor (RdCVF) secreted by rods and by insulin signaling. Together, the three cells act as symbiotes: the RPE supplies the glucose from the choroidal circulation to the photoreceptors, the rods help the cones, and both produce lactate to feed the RPE. In age-related macular degeneration this delicate ménage à trois is disturbed by the chronic infiltration of inflammatory macrophages. These immune cells also rely on aerobic glycolysis and compete for glucose and produce lactate. We here review the glucose metabolism in the homeostasis of the outer retina and in macrophages and hypothesize what happens when the metabolism of photoreceptors and the RPE is disturbed by chronic inflammation.

scholarly journals Beyond AREDS Formulations, What Is Next for Intermediate Age-Related Macular Degeneration (iAMD) Treatment? Potential Benefits of Antioxidant and Anti-inflammatory Apocarotenoids as Neuroprotectors

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Serge Camelo ◽  
Mathilde Latil ◽  
Stanislas Veillet ◽  
Pierre J. Dilda ◽  
René Lafont
Keyword(s):  
Macular Degeneration ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Crocus Sativus ◽  
Subretinal Space ◽  
Major Health Problem ◽  
Age Related

Age-related macular degeneration (AMD) is the commonest cause of severe visual loss and blindness in developed countries among individuals aged 60 and older. AMD slowly progresses from early AMD to intermediate AMD (iAMD) and ultimately late-stage AMD. Late AMD encompasses either neovascular AMD (nAMD) or geographic atrophy (GA). nAMD is defined by choroidal neovascularization (CNV) and hemorrhage in the subretinal space at the level of the macula. This induces a rapid visual impairment caused by the death of photoreceptor cells. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibodies is the standard treatment of nAMD but adds to the burden of patient care. GA is characterized by slowly expanding photoreceptor, and retinal pigment epithelium (RPE) degeneration patches progressively leading to blindness. There is currently no therapy to cure GA. Late AMD continues to be an unmet medical need representing a major health problem with millions of patients worldwide. Oxidative stress and inflammation are recognized as some of the main risk factors to developing late AMD. The antioxidant formulation AREDS (Age-Related Eye Disease Studies), contains β-carotene, which has been replaced by lutein and zeaxanthin in AREDS2, are given to patients with iAMD but have a limited effect on the incidence of nAMD and GA. Thus, to avoid or slowdown the development of late stages of AMD (nAMD or GA), new therapies targeting iAMD are needed such as crocetin obtained through hydrolysis of crocin, an important component of saffron (Crocus sativus L.), and norbixin derived from bixin extracted from Bixa orellana seeds. We have shown that these apocarotenoids preserved more effectively RPE cells against apoptosis following blue light exposure in the presence of A2E than lutein and zeaxanthin. In this review, we will discuss the potential use of apocarotenoids to slowdown the progression of iAMD, to reduce the incidence of both forms of late AMD.

scholarly journals Potential Sources and Roles of Adaptive Immunity in Age-Related Macular Degeneration: Shall We Rename AMD into Autoimmune Macular Disease?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Serge Camelo
Keyword(s):  
T Cells ◽  
Macular Degeneration ◽  
Retinal Degeneration ◽  
Adaptive Immunity ◽  
Choroidal Neovascularization ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Pathologic Features

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly throughout the industrialized world. Its most prominent pathologic features are lesions involving the retinal pigment epithelium (RPE) the Bruch’s membrane, the degeneration of photoreceptors, and, in the most aggressive cases, choroidal neovascularization. Genetic associations between the risk of developing AMD and polymorphism within components of the complement system, as well as chemokine receptors expressed on microglial cells and macrophages, have linked retinal degeneration and choroidal neovascularization to innate immunity (inflammation). In addition to inflammation, players of the adaptive immunity including cytokines, chemokines, antibodies, and T cells have been detected in animal models of AMD and in patients suffering from this pathology. These observations suggest that adaptive immunity might play a role in different processes associated with AMD such as RPE atrophy, neovascularization, and retinal degeneration. To this date however, the exact roles (if any) of autoantibodies and T cells in AMD remain unknown. In this review we discuss the potential effects of adaptive immune responses in AMD pathogenesis.

scholarly journals Autophagy: A new insight into pathogenesis and treatment possibilities in age-related macular degeneration

2020 ◽  
Vol 74 ◽  
pp. 213-223
Author(s):  
Agnieszka Kubicka-Trząska ◽  
Izabella Karska-Basta ◽  
Katarzyna Żuber-Łaskawiec
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Therapeutic Modalities ◽  
Central Vision Loss ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
The Impact ◽  
Insight Into

Age-related macular degeneration (AMD) is a significant problem in healthcare, because it is a leading cause of central vision loss in individuals over 50 years old in well-developed countries. Pathogenesis of AMD is multifactorial and still not completely understood. Proven risk factors include the following: natural senescence of retina, oxidative stress, complement activation, chronic subretinal inflammatory reaction, genetic and environmental factors. Data on links between autophagy and AMD development are being raised. Autophagy is a cellular process involving the degradation of long-lived proteins and damaged fragments and components of cells; it is responsible for the maintenance of dynamic intracellular homeostasis and it enables cell survival under stress conditions. Disturbances of autophagy mechanisms, i.e. its activation or inhibition, may lead to the development of many various pathologies. Thus, autophagy plays a dual role, as a mechanism responsible for protecting or killing cells. The paper describes autophagy mechanisms and their role in the natural process of retinal cells senescence and presents the autophagy impairment as a crucial cause of AMD development. We also describe the impact of intravitreal anti-VEGF therapy on retinal autophagy mechanisms and potential new therapeutic modalities for AMD based on autophagy modulation.

scholarly journals Apolipoprotein E isoform-specific phase transitions in the retinal pigment epithelium drive disease phenotypes in age-related macular degeneration

2020 ◽  
Author(s):  
Nilsa La Cunza ◽  
Li Xuan Tan ◽  
Gurugirijha Rathnasamy ◽  
Thushara Thamban ◽  
Colin J. Germer ◽  
...  
Keyword(s):  
Phase Transitions ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Human Donor ◽  
Age Related ◽  
Histopathological Studies

AbstractThe retinal pigment epithelium (RPE) is the site of initial damage leading to photoreceptor degeneration and vision loss in age-related macular degeneration (AMD). Genetic and histopathological studies implicate cholesterol dysregulation in AMD; yet mechanisms linking cholesterol to RPE injury and drusen formation remain poorly understood. Especially enigmatic are allelic variants of the cholesterol transporter APOE, major risk modifiers in Alzheimer’s disease that show reversed risk associations with AMD. Here, we investigated how ApoE isoforms modulate RPE health using live-cell imaging of primary RPE cultures and high-resolution imaging of human donor tissue. We show that the AMD-protective ApoE4 efficiently transports cholesterol and safeguards RPE homeostasis despite cellular stress. In contrast, ApoE2-expressing RPE accumulate cholesterol, which promotes autophagic deficits and complement-mediated mitochondrial fragmentation. Redox-related order-disorder phase transitions in ApoE2 drive the formation of intracellular biomolecular condensates as potential drusen precursors. Drugs that restore mitochondrial function limit condensate formation in ApoE2-RPE. Autophagic and mitochondrial defects correlate with intracellular ApoE aggregates in AMD donor RPE. Our study elucidates how AMD risk variants act as tipping points to divert the RPE from normal aging towards AMD by disrupting critical metabolic functions, and identifies mitochondrial stress-mediated aberrant phase transitions as a novel mechanism of drusen biogenesis.

scholarly journals Fully-automated atrophy segmentation in dry age-related macular degeneration in optical coherence tomography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasmine Derradji ◽  
Agata Mosinska ◽  
Stefanos Apostolopoulos ◽  
Carlos Ciller ◽  
Sandro De Zanet ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Layer ◽  
Optical Coherence ◽  
Age Related ◽  
Layer Segmentation

AbstractAge-related macular degeneration (AMD) is a progressive retinal disease, causing vision loss. A more detailed characterization of its atrophic form became possible thanks to the introduction of Optical Coherence Tomography (OCT). However, manual atrophy quantification in 3D retinal scans is a tedious task and prevents taking full advantage of the accurate retina depiction. In this study we developed a fully automated algorithm segmenting Retinal Pigment Epithelial and Outer Retinal Atrophy (RORA) in dry AMD on macular OCT. 62 SD-OCT scans from eyes with atrophic AMD (57 patients) were collected and split into train and test sets. The training set was used to develop a Convolutional Neural Network (CNN). The performance of the algorithm was established by cross validation and comparison to the test set with ground-truth annotated by two graders. Additionally, the effect of using retinal layer segmentation during training was investigated. The algorithm achieved mean Dice scores of 0.881 and 0.844, sensitivity of 0.850 and 0.915 and precision of 0.928 and 0.799 in comparison with Expert 1 and Expert 2, respectively. Using retinal layer segmentation improved the model performance. The proposed model identified RORA with performance matching human experts. It has a potential to rapidly identify atrophy with high consistency.

scholarly journals Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Majda Hadziahmetovic ◽  
Goldis Malek
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Clinical Care ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.

scholarly journals Ophthalmic artery angioplasty for age-related macular degeneration

2022 ◽  
pp. neurintsurg-2021-018222
Author(s):  
Ivan Lylyk ◽  
Carlos Bleise ◽  
Pedro N Lylyk ◽  
Nicolas Perez ◽  
Javier Lundquist ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Late Stage ◽  
Ophthalmic Artery ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Patient Reports ◽  
Age Related ◽  
Clinically Significant

BackgroundThere is considerable overlap of contributors to cardiovascular disease and the development of age-related macular degeneration (AMD). Compromised ocular microcirculation due to aging and vascular disease contribute to retinal dysfunction and vision loss. Decreased choroidal perfusion is evident in eyes with dry AMD and is thought to play a role in retinal pigment epithelial dysfunction, the rate of development of geographic atrophy, and the development of neovascularization. The aim of the study was to demonstrate that AMD is correlated with a compromised blood flow in the ocular pathway and show OA angioplasty as a potential treatment of late-stage AMD.MethodsBased on the potential for the ophthalmic artery (OA) to be an anatomical target for the treatment of AMD as outlined above, five patients were found to be eligible for compassionate use treatment, presenting clinically significant late-stage AMD with profound vision loss in one or both eyes, and are included in this retrospective study.ResultsOA narrowing, or significant calcium burden at the ophthalmic segment of the internal carotid artery compromising the origin of the OA was confirmed in all cases. Subsequent OA cannulation was achieved in all patients with some difficulty. Subjective patient reports indicated that all patients perceived a benefit following the procedure; however, improved postoperative visual acuity did not confirm that perceived benefit for one of the patients.ConclusionsFeasibility and safety of the OA angioplasty were demonstrated, and a benefit perceived in five patients with profound vision loss and a desire to achieve improved quality of life. A clinical trial with controlled schedule, imaging, and methodologies is needed to confirm these results.

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