scholarly journals Oxidative Stress and Microvascular Alterations in Diabetic Retinopathy: Future Therapies

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
María L. Rodríguez ◽  
Salvador Pérez ◽  
Salvador Mena-Mollá ◽  
M. Carmen Desco ◽  
Ángel Luis Ortega
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Diabetic Macular Oedema ◽  
Argon Laser ◽  
Developed Countries ◽  
Oral Antidiabetic Agents ◽  
Recommended Treatment ◽  
Diabetic Eye Disease ◽  
Advanced Stages

Diabetes is a disease that can be treated with oral antidiabetic agents and/or insulin. However, patients’ metabolic control is inadequate in a high percentage of them and a major cause of chronic diseases like diabetic retinopathy. Approximately 15% of patients have some degree of diabetic retinopathy when diabetes is first diagnosed, and most will have developed this microvascular complication after 20 years. Early diagnosis of the disease is the best tool to prevent or delay vision loss and reduce the involved costs. However, diabetic retinopathy is an asymptomatic disease and its development to advanced stages reduces the effectiveness of treatments. Today, the recommended treatment for severe nonproliferative and proliferative diabetic retinopathy is photocoagulation with an argon laser and intravitreal injections of anti-VEGF associated with, or not, focal laser for diabetic macular oedema. The use of these therapeutic approaches is severely limited, such as uncomfortable administration for patients, long-term side effects, the costs they incur, and the therapeutic effectiveness of the employed management protocols. Hence, diabetic retinopathy is the widespread diabetic eye disease and a leading cause of blindness in adults in developed countries. The growing interest in using polyphenols, e.g., resveratrol, in treatments related to oxidative stress diseases has spread to diabetic retinopathy. This review focuses on analysing the sources and effects of oxidative stress and inflammation on vascular alterations and diabetic retinopathy development. Furthermore, current and antioxidant therapies, together with new molecular targets, are postulated for diabetic retinopathy treatment.

Combination Approaches Targeting Neurodegeneration, Oxidative stress and Inflammation in the Treatment of Diabetic Retinopathy

2021 ◽  
Vol 22 ◽  
Author(s):  
Siddhi Dilip Chalke ◽  
Pravin Popatrao Kale
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Early Stages ◽  
Advanced Stages ◽  
Severe Vision Loss ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

: Diabetic Retinopathy (DR) is one of the most severe ocular problems of diabetes. It is a microvascular complication that impairs the vision of diabetic individuals and can cause acquired blindness. Currently available treatment options like laser therapy, vitrectomy, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and glucocorticoids help to reduce vision loss at advanced stages. In spite of the available therapies, patients with severe vision loss face difficulty in achieving normal vision. There is a need for development of newer treatment strategies to address the condition from the early stages. Multiple factors owing to complex pathophysiological events are responsible for this long-term complication. Neurodegeneration, inflammation, and oxidative stress are the three important factors associated with the development of DR. Oxidative stress is a major contributor to the onset and progression of DR. Pathological events like retinal neurodegeneration and inflammation damage the retina right in the early stages of DR. Different combinations of treatments targeting these pathological events are discussed in the present review. The first combination discussed is citicoline and resveratrol. The second combination is duloxetine and N-acetyl cysteine (NAC). These combinations may help in the early stages of DR. CD5-2 and angiopoietin-2 inhibitors is the third combination. This combination may help to manage diabetic macular edema. The main purpose of this article is to discuss the link between these pathologies and the three combination approaches with the objective of consideration of newer therapeutic approaches in research related to DR treatment.

scholarly journals Effectiveness of interventions to increase uptake and completion of treatment for diabetic retinopathy in low- and middle-income countries: a rapid review protocol.

2020 ◽  
Author(s):  
Covadonga Bascaran ◽  
Nyawira Mwangi ◽  
Fabrizio D’Esposito ◽  
Charles Cleland ◽  
Iris Gordon ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
English Language ◽  
Vision Loss ◽  
Data Extraction ◽  
Treatment Protocol ◽  
Diabetic Macular Oedema ◽  
Rapid Review ◽  
Middle Income ◽  
Recommended Treatment ◽  
Review Protocol

Abstract Background Vision loss due to diabetic retinopathy can largely be prevented or delayed through treatment. Patients with vision-threatening diabetic retinopathy are typically offered laser or intravitreal injections which often require more than one treatment cycle. However, treatment is not always initiated, or it is not completed, resulting in poor visual outcomes. Interventions aimed at improving the uptake or completion of treatment for diabetic retinopathy can potentially help prevent or delay visual loss in people with diabetes. Methods We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting interventions to improve the uptake of treatment for diabetic retinopathy (DR) and/or diabetic macular oedema (DMO), compared with usual care, in adults with diabetes. The review will include studies published in the last 20 years in the English language. We will include any study design that measured any of the following outcomes in relation to treatment uptake and completion for DR and/or DMO: 1) Proportion of patients initiating treatment for DR and/or DMO among those to whom it is recommended, 2) Proportion of patients completing treatment for DR and/or DMO among those to whom it is recommended, 3)Proportion of patients completing treatment for DR and/or DMO among those initiating treatment, 4) Number and proportion of DR and/or DMO rounds from the recommended treatment protocol completed per patient. For included studies we will also report any measures of cost-effectiveness when available. Two reviewers will screen search results independently. Risk of bias assessment and data extraction will be done by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. Discussion This rapid review aims to identify and synthesise the peer-reviewed literature on the effectiveness of interventions to increase uptake and completion of treatment for DR and/or DMO in LMICs. The rapid review methodology was chosen in order to rapidly synthesise the available evidence to support program implementers and policy makers in designing evidence-based health programs, public health policy, and inform the allocation of resources. Rapid review registration OSF: osf.io/h5wgr

scholarly journals Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1683
Author(s):  
Milagros Mateos-Olivares ◽  
Luis García-Onrubia ◽  
Fco. Javier Valentín-Bravo ◽  
Rogelio González-Sarmiento ◽  
Maribel Lopez-Galvez ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Standard Therapy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Rho Kinase ◽  
Diabetic Macular Oedema ◽  
New Drugs ◽  
Anti Vegf

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

scholarly journals Oxidative Stress in Optic Neuropathies

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1538
Author(s):  
Berta Sanz-Morello ◽  
Hamid Ahmadi ◽  
Rupali Vohra ◽  
Sarkis Saruhanian ◽  
Kristine Karla Freude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Redox System ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oxidative Stress Biomarkers ◽  
Optic Disc Drusen ◽  
Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

New treatment strategies for diabetic eye disease

2020 ◽  
pp. 179-184
Author(s):  
Sobha Joseph ◽  
Ramesh R. Sivaraj
Keyword(s):  
Treatment Strategies ◽  
Diabetic Macular Oedema ◽  
Argon Laser ◽  
Fluocinolone Acetonide ◽  
Drug Molecules ◽  
The United Kingdom ◽  
Anti Vegf ◽  
Diabetic Eye Disease ◽  
Control Of Diabetes ◽  
New Treatment

Argon laser treatment was the mainstay of treatment for diabetic retinopathy (DR) and maculopathy up to the last decade. However, with the better understanding of pathophysiology of DR, newer medications have become available. Anti-vascular endothelial growth factors (anti-VEGF) and steroid implants for vision-threatening diabetic macular oedema have been widely adopted in clinical practice with several longer-acting drug molecules in the pipeline. In the United Kingdom, ranibizumab and aflibercept are licensed anti-VEGF drugs. Dexamethasone and fluocinolone acetonide implants are the steroids that are available. The emphasis on systemic control of diabetes and blood pressure remains very relevant even in the era of these newer drugs.

Role of Oxidative Stress in Diabetic Retinopathy and the Beneficial Effects of Flavonoids

2018 ◽  
Vol 24 (19) ◽  
pp. 2180-2187 ◽  
Author(s):  
Mohammad Shamsul Ola ◽  
Dalia Al-Dosari ◽  
Abdullah S. Alhomida
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Experimental Studies ◽  
Developed Countries ◽  
Retinal Damage ◽  
Beneficial Effects ◽  
Diabetic Retina ◽  
Retinal Pathology ◽  
Dietary Flavonoids

Diabetic Retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious change through dysregulation of cellular physiology that damages both neuronal and vascular cells. In this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contribute to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by our group and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the beneficial effects of the six major flavonoid families, such as flavanones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flavanoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in diabetes. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR.

scholarly journals Extracellular Vesicles and MicroRNA: Putative Role in Diagnosis and Treatment of Diabetic Retinopathy

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 705 ◽  
Author(s):  
Beatriz Martins ◽  
Madania Amorim ◽  
Flávio Reis ◽  
António Francisco Ambrósio ◽  
Rosa Fernandes
Keyword(s):  
Diabetic Retinopathy ◽  
Extracellular Vesicles ◽  
Vision Loss ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Communication ◽  
Cell Junctions ◽  
Low Grade ◽  
Long Distance ◽  
Advanced Stages

Diabetic retinopathy (DR) is a complex, progressive, and heterogenous retinal degenerative disease associated with diabetes duration. It is characterized by glial, neural, and microvascular dysfunction, being the blood-retinal barrier (BRB) breakdown a hallmark of the early stages. In advanced stages, there is formation of new blood vessels, which are fragile and prone to leaking. This disease, if left untreated, may result in severe vision loss and eventually legal blindness. Although there are some available treatment options for DR, most of them are targeted to the advanced stages of the disease, have some adverse effects, and many patients do not adequately respond to the treatment, which demands further research. Oxidative stress and low-grade inflammation are closely associated processes that play a critical role in the development of DR. Retinal cells communicate with each other or with another one, using cell junctions, adhesion contacts, and secreted soluble factors that can act in neighboring or long-distance cells. Another mechanism of cell communication is via secreted extracellular vesicles (EVs), through exchange of material. Here, we review the current knowledge on deregulation of cell-to-cell communication through EVs, discussing the changes in miRNA expression profiling in body fluids and their role in the development of DR. Thereafter, current and promising therapeutic agents for preventing the progression of DR will be discussed.

Diabetic Retinopathy—Update on Prevention Techniques, Present Therapies, and New Leads

2014 ◽  
Vol 10 (01) ◽  
pp. 25
Author(s):  
Lauren M Marozas ◽  
Patrice E Fort ◽  
◽  
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Developed Countries ◽  
Detection Methods ◽  
Retinal Microvasculature ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Combined Control ◽  
Working Age ◽  
Proactive Measures

Diabetic retinopathy is the major ocular complication associated with diabetes, and represents the leading cause of legal blindness in the working-age population of developed countries. Although classically diagnosed based on abnormalities of the retinal microvasculature, diabetic retinopathy is now widely recognized as a neurovascular disease. While all patients with diabetes are at increased risk for eye disease including diabetic retinopathy, proactive measures, and timely intervention can prevent or delay subsequent vision loss. Systemic management of diabetes by combined control of glycemia, blood pressure, and serum lipid levels remains the most important method of preventing diabetic retinopathy onset and progression. Once detected, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection can help preserve vision. However, the need for improved detection methods and therapies that will allow earlier diagnosis and treatment remains apparent. This review summarizes current techniques for the prevention and intervention for diabetic retinopathy, and examines ongoing developments in the search for new endpoints and therapies as they apply to preventing vision loss associated with diabetes.

scholarly journals Diabetic retinopathy: treatment and prevention

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S9-S11 ◽  
Author(s):  
Paul M Dodson
Keyword(s):  
Diabetic Retinopathy ◽  
Standard Therapy ◽  
Vision Loss ◽  
Early Stage ◽  
Developed Countries ◽  
Relative Reduction ◽  
Treatment And Prevention ◽  
Working Age ◽  
Capillary Occlusion

Diabetic eye disease is the major cause of blindness and vision loss among working-age people in developed countries. Microangiopathy and capillary occlusion underlie the pathogenesis of disease. While laser treatment is regarded as the standard therapy, intensive medical management of glycaemia and hypertension is also a priority in order to reduce the risk of diabetic retinopathy. Recent data have prompted a re-evaluation of the role of lipid-modifying therapy in reducing diabetic retinopathy. The Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study demonstrated a significant 30% relative reduction in the need for first retinal laser therapy in patients with (predominantly early-stage) type 2 diabetes treated with fenofibrate 200 mg daily, from 5.2% with placebo to 3.6% with fenofibrate, p=0.0003. The benefit of fenofibrate was evident within the first year of treatment. These promising data justify further evaluation of the mechanism and role of fenofibrate, in addition to standard therapy, in the management of diabetic retinopathy.

scholarly journals Reduction of Glut1 in retinal neurons but not the RPE alleviates polyol accumulation and normalizes early characteristics of diabetic retinopathy

2020 ◽  
Author(s):  
Nicholas C. Holoman ◽  
Jacob J. Aiello ◽  
Timothy D. Trobenter ◽  
Matthew J. Tarchick ◽  
Michael R. Kozlowski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Aldose Reductase ◽  
Glucose Transporter ◽  
Vision Loss ◽  
Significant Proportion ◽  
Diabetic Patients ◽  
Retinal Neurons ◽  
Anti Vegf ◽  
Facilitative Glucose Transporter

AbstractHyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway. Therapies to reduce retinal polyol accumulation for the prevention of DR have been elusive due to low sorbitol dehydrogenase levels in the retina and inadequate inhibition of aldose reductase. Using systemic and conditional genetic inactivation, we targeted the primary facilitative glucose transporter in the retina, Glut1, as a preventative therapeutic in diabetic male and female mice. Unlike wildtype diabetics, diabetic Glut1+/− mice did not display elevated Glut1 levels in the retina. Furthermore, diabetic Glut1+/− mice exhibited ameliorated ERG defects, inflammation and oxidative stress, which was correlated with a significant reduction in retinal sorbitol accumulation. RPE-specific reduction of Glut1 did not prevent an increase in retinal sorbitol content or early hallmarks of DR. However, like diabetic Glut1+/− mice, reduction of Glut1 specifically in retinal neurons mitigated polyol accumulation and completely prevented retinal dysfunction and the elevation of markers for oxidative stress and inflammation associated with diabetes. These results suggest that modulation of retinal polyol accumulation via Glut1 in photoreceptors can circumvent the difficulties in regulating systemic glucose metabolism and be exploited to prevent DR.SignificanceDiabetic retinopathy (DR) affects one third of diabetic patients and is the primary cause of vision loss in adults aged 20-74. While anti-VEGF and photocoagulation treatments for the late-stage vision threatening complications can prevent vision loss, a significant proportion of patients do not respond to anti-VEGF therapies and mechanisms to stop progression of early-stage symptoms remain elusive. Glut1 is the primary facilitative glucose transporter for the retina. We determined that a moderate reduction in Glut1 levels, specifically in retinal neurons, but not the RPE, was sufficient to prevent retinal polyol accumulation and the earliest functional defects to be identified in the diabetic retina. Our study defines modulation of Glut1 in retinal neurons as a targetable molecule for prevention of DR.

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