scholarly journals Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 905 ◽  
Author(s):  
David J. Miller ◽  
M. Ariel Cascio ◽  
Mariana G. Rosca
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Neurovascular Unit ◽  
Microvascular Disease ◽  
Retinal Disease ◽  
Neural Retina ◽  
Vascular Pathology ◽  
Future Research ◽  
Substrate Selection ◽  
Working Age

Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diagnosis is based on vascular pathology, DR is associated with early abnormalities in the electroretinogram, indicating alterations of the neural retina and impaired visual signaling. The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways through the retinal neurovascular unit. There is evidence that microvascular disease in DR is caused in part by altered energetic metabolism in the neural retina and specifically from signals originating in the photoreceptors. In this review, we discuss the main pathogenic mechanisms that link alterations in neural retina bioenergetics with vascular regression in DR. We focus specifically on the recent developments related to alterations in mitochondrial metabolism including energetic substrate selection, mitochondrial function, oxidation-reduction (redox) imbalance, and oxidative stress, and critically discuss the mechanisms of these changes and their consequences on retinal function. We also acknowledge implications for emerging therapeutic approaches and future research directions to find novel mitochondria-targeted therapeutic strategies to correct bioenergetics in diabetes. We conclude that retinal bioenergetics is affected in the early stages of diabetes with consequences beyond changes in ATP content, and that maintaining mitochondrial integrity may alleviate retinal disease.

scholarly journals Acrolein: A Potential Mediator of Oxidative Damage in Diabetic Retinopathy

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1579 ◽  
Author(s):  
Moaddey Alfarhan ◽  
Eissa Jafari ◽  
S. Priya Narayanan
Keyword(s):  
Diabetic Retinopathy ◽  
Oxidative Damage ◽  
Vision Loss ◽  
Critical Role ◽  
Neurovascular Unit ◽  
Antioxidant Properties ◽  
Therapeutic Interventions ◽  
Diabetic Retina ◽  
Working Age ◽  
The Impact

Diabetic retinopathy (DR) is the leading cause of vision loss among working-age adults. Extensive evidences have documented that oxidative stress mediates a critical role in the pathogenesis of DR. Acrolein, a product of polyamines oxidation and lipid peroxidation, has been demonstrated to be involved in the pathogenesis of various human diseases. Acrolein’s harmful effects are mediated through multiple mechanisms, including DNA damage, inflammation, ROS formation, protein adduction, membrane disruption, endoplasmic reticulum stress, and mitochondrial dysfunction. Recent investigations have reported the involvement of acrolein in the pathogenesis of DR. These studies have shown a detrimental effect of acrolein on the retinal neurovascular unit under diabetic conditions. The current review summarizes the existing literature on the sources of acrolein, the impact of acrolein in the generation of oxidative damage in the diabetic retina, and the mechanisms of acrolein action in the pathogenesis of DR. The possible therapeutic interventions such as the use of polyamine oxidase inhibitors, agents with antioxidant properties, and acrolein scavengers to reduce acrolein toxicity are also discussed.

scholarly journals RORγt Inhibitor-SR1001 Halts Retinal Inflammation, Capillary Degeneration, and the Progression of Diabetic Retinopathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3547
Author(s):  
Thomas E. Zapadka ◽  
Sarah I. Lindstrom ◽  
Brooklyn E. Taylor ◽  
Chieh A. Lee ◽  
Jie Tang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Microvascular Disease ◽  
Orphan Receptor ◽  
Vascular Pathology ◽  
Diabetic Mice ◽  
Molecule Inhibitor ◽  
Working Age ◽  
Endothelial Cell Death ◽  
Retinal Inflammation ◽  
Capillary Degeneration

Diabetic retinopathy is a diabetes-mediated retinal microvascular disease that is the leading cause of blindness in the working-age population worldwide. Interleukin (IL)-17A is an inflammatory cytokine that has been previously shown to play a pivotal role in the promotion and progression of diabetic retinopathy. Retinoic acid-related orphan receptor gammaT (RORγt) is a ligand-dependent transcription factor that mediates IL-17A production. However, the role of RORγt in diabetes-mediated retinal inflammation and capillary degeneration, as well as its potential therapeutic attributes for diabetic retinopathy has not yet been determined. In the current study, we examined retinal inflammation and vascular pathology in streptozotocin-induced diabetic mice. We found RORγt expressing cells in the retinal vasculature of diabetic mice. Further, diabetes-mediated retinal inflammation, oxidative stress, and retinal endothelial cell death were all significantly lower in RORγt−/− mice. Finally, when a RORγt small molecule inhibitor (SR1001) was subcutaneously injected into diabetic mice, retinal inflammation and capillary degeneration were ameliorated. These findings establish a pathologic role for RORγt in the onset of diabetic retinopathy and identify a potentially novel therapeutic for this blinding disease.

scholarly journals Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Shen Nian ◽  
Amy C. Y. Lo ◽  
Yajing Mi ◽  
Kai Ren ◽  
Di Yang
Keyword(s):  
Diabetic Retinopathy ◽  
Early Stage ◽  
Neurovascular Unit ◽  
Microvascular Disease ◽  
Industrialized Countries ◽  
Novel Treatments ◽  
Microvascular Changes ◽  
Working Age ◽  
Retinal Neurodegeneration ◽  
The Common

AbstractDiabetic retinopathy (DR), one of the common complications of diabetes, is the leading cause of visual loss in working-age individuals in many industrialized countries. It has been traditionally regarded as a purely microvascular disease in the retina. However, an increasing number of studies have shown that DR is a complex neurovascular disorder that affects not only vascular structure but also neural tissue of the retina. Deterioration of neural retina could precede microvascular abnormalities in the DR, leading to microvascular changes. Furthermore, disruption of interactions among neurons, vascular cells, glia and local immune cells, which collectively form the neurovascular unit, is considered to be associated with the progression of DR early on in the disease. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse retinal neurodegeneration, neuroinflammation and impaired cell-cell interactions of the neurovascular unit in early stage DR. Here, we present current perspectives on the pathophysiology of DR as a neurovascular disease, especially at the early stage. Potential novel treatments for preventing or reversing neurovascular injuries in DR are discussed as well.

scholarly journals Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease

2021 ◽  
Vol 10 (6) ◽  
pp. 1254
Author(s):  
Warren W. Pan ◽  
Thomas W. Gardner ◽  
Jennifer L. Harder
Keyword(s):  
Systems Biology ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Vision Loss ◽  
Retinal Disease ◽  
Diabetic Kidney ◽  
New Therapies ◽  
Traditional Research ◽  
Working Age ◽  
Culture Models

Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models—a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual’s specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.

scholarly journals A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2441
Author(s):  
Drake W. Lem ◽  
Dennis L. Gierhart ◽  
Pinakin Gunvant Davey
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Microvascular Disease ◽  
Age Related Macular Degeneration ◽  
Cell Degeneration ◽  
Neuroprotective Effects ◽  
Age Related ◽  
Induced Changes ◽  
Dietary Carotenoid

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

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 The Evolving Treatment Options for Diabetic Macular Edema

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Atul Jain ◽  
Neeta Varshney ◽  
Colin Smith
Keyword(s):  
Diabetic Retinopathy ◽  
Visual Impairment ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Treatment Options ◽  
Previous Treatment ◽  
Common Cause ◽  
Working Age

Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, and diabetic macular edema (DME) is the most common cause of visual impairment in individuals with DR. This review focuses on the pathophysiology, previous treatment paradigms, and emerging treatment options in the management of DME.

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 Diabetic Retinopathy, lncRNAs, and Inflammation: A Dynamic, Interconnected Network

2019 ◽  
Vol 8 (7) ◽  
pp. 1033 ◽  
Author(s):  
Saumik Biswas ◽  
Marie Sarabusky ◽  
Subrata Chakrabarti
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Interconnected Network ◽  
Working Age ◽  
Modulation Of Gene Expression ◽  
Non Coding Rnas ◽  
Working Age Population ◽  
Prevalence Of Diabetes Mellitus

Diabetic retinopathy (DR) is reaching epidemic levels globally due to the increase in prevalence of diabetes mellitus (DM). DR also has detrimental effects to quality of life, as it is the leading cause of blindness in the working-age population and the most common cause of vision loss in individuals with DM. Over several decades, many studies have recognized the role of inflammation in the development and progression of DR; however, in recent years, accumulating evidence has also suggested that non-coding RNAs, especially long non-coding (lncRNAs), are aberrantly expressed in diabetes and may play a putative role in the development and progression of DR through the modulation of gene expression at the transcriptional, post-transcriptional, or epigenetic level. In this review, we will first highlight some of the key inflammatory mediators and transcription factors involved in DR, and we will then introduce the critical roles of lncRNAs in DR and inflammation. Following this, we will discuss the implications of lncRNAs in other epigenetic mechanisms that may also contribute to the progression of inflammation in DR.

scholarly journals PREVALENCE, PATHOGENESIS, CLASSIFICATION, IMAGING, SCREENING AND MANAGE-MENT OF DIABETIC RETINOPATHY- A CRITICAL REVIEW

2021 ◽  
Vol 9 (7) ◽  
pp. 1433-1442
Author(s):  
Narender Chanchal ◽  
Kushagra Goyal ◽  
Divya Vij ◽  
Rajesh Kumar Mishra
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
International Diabetes Federation ◽  
Pathological Process ◽  
Heterogeneous Cluster ◽  
Keywords Diabetic Retinopathy ◽  
Screening And Surveillance ◽  
Working Age ◽  
Microvascular Alterations

Diabetic retinopathy is that the leading reason for sightlessness among people between twenty-five and seventyfour years older within the industrialised world. Diabetes mellitus (DM) includes a heterogeneous cluster of disorders of carbohydrate, protein, and metastasis manifesting hyperglycemia. Diabetic retinopathy could be microangiopathy ensuing from the chronic effects of the disease, and shares similarities with the microvascular alterations that occur in different tissues at risk of DM equivalent to the kidneys and also the peripheral nerves. Diabetic retinopathy is assessed into nonproliferative and proliferative stages. Nonproliferative diabetic retinopathy (NPDR) involves progressive intraretinal microvascular alterations that may result in, and a lot of advanced proliferative stages outlined by extraretinal neovascularization. Imaging modalities in common clinical use for the management of NPDR and DME embrace structure photography, fluorescein angiography (FA), and optical coherence tomography (OCT). The suggested schedule for screening and surveillance for NPDR reflects data concerning the epidemiology and natural history of the disease. Diabetic retinopathy could be a leading explanationfor vision loss in working-age Americans and a major cause of sightlessness worldwide. The International Diabetes Federation estimates that as several as 592 million individuals worldwide can have DM in 2035, a rise from or so 387 million people calculable to possess the disease in 2014. Here, we tend to present a review of the presentunderstanding and new insights into biochemical mechanisms within the pathological process in DR, classification, furthermore as clinical treatments for DR patients. Keywords: Diabetic retinopathy, diabetes mellitus, retinal degeneration, fluoresces in angiography, optical coher- ence tomography, VEGF, focal/grid laser photocoagulation.

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