The Blood–Retinal Barrier in Retinal Disease

2009 ◽  
Vol 03 (02) ◽  
pp. 105 ◽  
Author(s):  
José Cunha-Vaz ◽  
Keyword(s):  
Diabetic Retinopathy ◽  
Tight Junctions ◽  
Retinal Pigment ◽  
Water Flux ◽  
Retinal Disease ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Blood Retinal Barrier ◽  
Age Related

The blood–ocular barrier system is formed by two main barriers: the blood–aqueous barrier and the blood–retinal barrier (BRB). The BRB is particularly tight and restrictive and is a physiological barrier that regulates ion, protein and water flux into and out of the retina. The BRB consists of inner and outer components, the inner BRB being formed of tight junctions between retinal capillary endothelial cells and the outer BRB of tight junctions between retinal pigment epithelial cells. The BRB is essential to maintaining the eye as a privileged site and is essential for normal visual function. Alterations of the BRB play a crucial role in the development of retinal diseases. The two most frequent and relevant retinal diseases, diabetic retinopathy and age-related macular degeneration (AMD), are directly associated with alterations of the BRB. Diabetic retinopathy is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration of the outer BRB. Treatment of retinal diseases must also deal with the BRB either by using its specific transport mechanisms or by circumventing it through intravitreal injections

Gene editing prospects for treating inherited retinal diseases

2019 ◽  
Vol 57 (7) ◽  
pp. 437-444 ◽  
Author(s):  
Daniela Benati ◽  
Clarissa Patrizi ◽  
Alessandra Recchia
Keyword(s):  
Genome Editing ◽  
Genetic Disorder ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Genetic Defect ◽  
Retinal Dystrophy ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related

Retinal diseases (RD) include inherited retinal dystrophy (IRD), for example, retinitis pigmentosa and Leber’s congenital amaurosis, or multifactorial forms, for example, age-related macular degeneration (AMD). IRDs are clinically and genetically heterogeneous in nature. To date, more than 200 genes are known to cause IRDs, which perturb the development, function and survival of rod and cone photoreceptors or retinal pigment epithelial cells. Conversely, AMD, the most common cause of blindness in the developed world, is an acquired disease of the macula characterised by progressive visual impairment. To date, available therapeutic approaches for RD include nutritional supplements, neurotrophic factors, antiangiogenic drugs for wet AMD and gene augmentation/interference strategy for IRDs. However, these therapies do not aim at correcting the genetic defect and result in inefficient and expensive treatments. The genome editing technology based on clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) and an RNA that guides the Cas protein to a predetermined region of the genome, represents an attractive strategy to tackle IRDs without available cure. Indeed, CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease, representing a molecular tool to cure a genetic disorder. In this review, we will introduce the mechanism of CRISPR/Cas system, presenting an updated panel of Cas variants and delivery systems, then we will focus on applications of CRISPR/Cas genome editing in the retina, and, as emerging treatment options, in patient-derived induced pluripotent stem cells followed by transplantation of retinal progenitor cells into the eye.

scholarly journals Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage

2021 ◽  
Vol 22 (2) ◽  
pp. 600
Author(s):  
Gian Marco Tosi ◽  
Daniela Giustarini ◽  
Lorenzo Franci ◽  
Alberto Minetti ◽  
Francesco Imperatore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Ethyl Ester ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Rpe Cells ◽  
Age Related

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats’ eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.

Anti-Vegf in Management of Macular Edema in Retinal Disease

2017 ◽  
Vol 71 (1) ◽  
pp. 15-19
Author(s):  
Natasha T Shekerinov ◽  
Vesna Dimovska Jordanova ◽  
Milco Bogoev
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Vision Loss ◽  
Vascular Occlusion ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Anti Vegf ◽  
Age Related

Abstract Aim. To present new opportunities, clinical implications and benefits of the available VEGF therapy as a treatment of macular edema, which is a result of venous vascular occlusions, diabetic macular edema in diabetic retinopathy and age-related macular degeneration. Background. The pathophysiology of macular edema is complex and various processes are involved in its development. It is actually an abnormal retinal capillary permeability and a disorder in the blood retinal barrier, which only increases the vascular permeability. This causes an expansion of the extracellular spaces, which leads to fluid accumulation, which additionally leads to macular thickening and eventual vision loss. Methods. The studies included 40 patients, of whom17 was diagnosed with macular edema in diabetic retinopathy and were treated with anti-VEGF therapy. Also, there were 11 patients diagnosed with wet form of AMD, and 12 cases diagnosed with macular edema secondary to vein occlusion. This retrospective study of 18 months monitored the effects of visual acuity on Snellen chart and the effects of macula anatomy using Optical Coherent tomography /OCT/. All patients received intravitreal injection of Bevacizumab /Avastin/ of 1.25mg /0.04ml/ and were evaluated monthly or every 4 to 8weeks. We monitored the potential ocular and systematic side effects in all our cases. Results. In the first group which included patients with edema due to venous vascular occlusion improvement of visual acuity in 58.33% patients, 25.0% showed no change in visual acuity and 16.66% showed slight worsening of 0.029 and regression of CMT entirely to 393.22 after 4.6 intravitreal injections on average. In the second group there was no improvement of VA 0.172 and reducing central macular thickness for 218.34μm by 5.6 intravitreal applications. The third group, 17 patients with macular edema due to diabetic retinopathy had stabilization of visual acuity, i.e. slight improvement in 8 of them by 0.14; and, in 9 and improvement of 0.21 and regression CMT, an average of 174.3 μm. Although it has been shown that benefit of intravitreal use of Bevacizumab and improvement of visual acuity has not been always change hand in hand with the reduction of macular edema, the need for this kind of treatment in certain cases are needed to maintain stable CMT and VA in such patients. Conclusion. Over the last few years monoclonal antibodies have become a standard therapy in treatment of wet form of AMD. Switch on anti-VEGF drugs has shown significant results in clinical and visual out-comes in patients with changes of the macula as a result of other disease. In fact, they caused a revolution in the treatment of refractory macular edema.

scholarly journals A Splice Variant in SLC16A8 Gene Leads to Lactate Transport Deficit in Human iPS Cell-Derived Retinal Pigment Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 179
Author(s):  
Laurence Klipfel ◽  
Marie Cordonnier ◽  
Léa Thiébault ◽  
Emmanuelle Clérin ◽  
Frédéric Blond ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Lactate Transport ◽  
Ips Cell ◽  
Risk Alleles ◽  
Age Related ◽  
A Genome

Age-related macular degeneration (AMD) is a blinding disease for which most of the patients remain untreatable. Since the disease affects the macula at the center of the retina, a structure specific to the primate lineage, rodent models to study the pathophysiology of AMD and to develop therapies are very limited. Consequently, our understanding relies mostly on genetic studies highlighting risk alleles at many loci. We are studying the possible implication of a metabolic imbalance associated with risk alleles within the SLC16A8 gene that encodes for a retinal pigment epithelium (RPE)-specific lactate transporter MCT3 and its consequences for vision. As a first approach, we report here the deficit in transepithelial lactate transport of a rare SLC16A8 allele identified during a genome-wide association study. We produced induced pluripotent stem cells (iPSCs) from the unique patient in our cohort that carries two copies of this allele. After in vitro differentiation of the iPSCs into RPE cells and their characterization, we demonstrate that the rare allele results in the retention of intron 2 of the SLC16A8 gene leading to the absence of MCT3 protein. We show using a biochemical assay that these cells have a deficit in transepithelial lactate transport.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration

2021 ◽  
Vol 22 (13) ◽  
pp. 6800
Author(s):  
Maria Hytti ◽  
Eveliina Korhonen ◽  
Heidi Hongisto ◽  
Kai Kaarniranta ◽  
Heli Skottman ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Induced Pluripotent Stem Cell ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Protein Clearance ◽  
Age Related ◽  
Induced Pluripotent ◽  
Pigment Epithelial Cells

Inflammation is a key underlying factor of age-related macular degeneration (AMD) and inflammasome activation has been linked to disease development. Induced pluripotent stem-cell-derived retinal pigment epithelial cells (iPSC-RPE) are an attractive novel model system that can help to further elucidate disease pathways of this complex disease. Here, we analyzed the effect of dysfunctional protein clearance on inflammation and inflammasome activation in iPSC-RPE cells generated from a patient suffering from age-related macular degeneration (AMD) and an age-matched control. We primed iPSC-RPE cells with IL-1α and then inhibited both proteasomal degradation and autophagic clearance using MG-132 and bafilomycin A1, respectively, causing inflammasome activation. Subsequently, we determined cell viability, analyzed the expression levels of inflammasome-related genes using a PCR array, and measured the levels of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and MCP-1 secreted into the medium. Cell treatments modified the expression of 48 inflammasome-related genes and increased the secretion of mature IL-1β, while reducing the levels of IL-6 and MCP-1. Interestingly, iPSC-RPE from an AMD donor secreted more IL-1β and expressed more Hsp90 prior to the inhibition of protein clearance, while MCP-1 and IL-6 were reduced at both protein and mRNA levels. Overall, our results suggest that cellular clearance mechanisms might already be dysfunctional, and the inflammasome activated, in cells with a disease origin.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

scholarly journals Review of Subthreshold Diode Micropulse Laser Treatment for Retinal Diseases

2018 ◽  
Vol 1 (1) ◽  
pp. 62-70
Author(s):  
Juhn AT ◽  
Shyu AP ◽  
Benjamin J ◽  
Zhang Y
Keyword(s):  
Diabetic Retinopathy ◽  
Treatment Modality ◽  
Branch Retinal Vein Occlusion ◽  
Age Related Macular Degeneration ◽  
Clinical Settings ◽  
Retinal Diseases ◽  
Micropulse Laser ◽  
Vein Occlusion ◽  
Age Related ◽  
New Treatment

Subthreshold Diode Micropulse (SDM) laser is a relatively new treatment modality that confers very little to no anatomical risk to the retina. However, its efficacy is still being studied, and the scenario where SDM is most useful is still being elucidated. This paper reviews articles from 1997 to 2017 and reviews the settings, results, and outcomes of SDM in various clinical settings including diabetic macular edema, branch retinal vein occlusion, central serous Chorioretinopathy, proliferative diabetic retinopathy, and age-related macular degeneration.

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.

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