scholarly journals Novel Short-Chain Quinones to Treat Vision Loss in a Rat Model of Diabetic Retinopathy

2021 ◽  
Vol 22 (3) ◽  
pp. 1016
Author(s):  
Abraham Daniel ◽  
Dino Premilovac ◽  
Lisa Foa ◽  
Zikai Feng ◽  
Krupali Shah ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Internal Control ◽  
Rat Model ◽  
Vision Loss ◽  
Treatment Options ◽  
Short Chain ◽  
Vascular Pathology ◽  
Optokinetic Response ◽  
Drug Candidates

Diabetic retinopathy (DR), one of the leading causes of blindness, is mainly diagnosed based on the vascular pathology of the disease. Current treatment options largely focus on this aspect with mostly insufficient therapeutic long-term efficacy. Mounting evidence implicates mitochondrial dysfunction and oxidative stress in the central etiology of DR. Consequently, drug candidates that aim at normalizing mitochondrial function could be an attractive therapeutic approach. This study compared the mitoprotective compounds, idebenone and elamipretide, side-by-side against two novel short-chain quinones (SCQs) in a rat model of DR. The model effectively mimicked type 2 diabetes over 21 weeks. During this period, visual acuity was monitored by measuring optokinetic response (OKR). Vision loss occurred 5–8 weeks after the onset of hyperglycemia. After 10 weeks of hyperglycemia, visual function was reduced by 65%. From this point, the right eyes of the animals were topically treated once daily with the test compounds. The left, untreated eye served as an internal control. Only three weeks of topical treatment significantly restored vision from 35% to 58–80%, while visual acuity of the non-treated eyes continued to deteriorate. Interestingly, the two novel SCQs restored visual acuity better than idebenone or elamipretide. This was also reflected by protection of retinal pathology against oxidative damage, retinal ganglion cell loss, reactive gliosis, vascular leakage, and retinal thinning. Overall, mitoprotective and, in particular, SCQ-based compounds have the potential to be developed into effective and fast-acting drug candidates against DR.

scholarly journals Inhibition of Stat3 by a Small Molecule Inhibitor Slows Vision Loss in a Rat Model of Diabetic Retinopathy

2017 ◽  
Vol 58 (4) ◽  
pp. 2095 ◽  
Author(s):  
Phillip A. Vanlandingham ◽  
Didier J. Nuno ◽  
Alexander B. Quiambao ◽  
Eric Phelps ◽  
Ronald A. Wassel ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Small Molecule ◽  
Rat Model ◽  
Vision Loss ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

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 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.

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 Survival Time of Visual Gains after Diabetic Vitrectomy and Its Relationship with Ischemic Heart Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 310
Author(s):  
Abdah Khairiah Che Md Noor ◽  
Evelyn Li Min Tai ◽  
Yee Cheng Kueh ◽  
Ab Hamid Siti-Azrin ◽  
Zamri Noordin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Survival Time ◽  
Proliferative Diabetic Retinopathy ◽  
Vision Loss ◽  
Ischemic Heart ◽  
Vitrectomy Surgery

Vitrectomy surgery in proliferative diabetic retinopathy improves the vision-related quality of life. However, there is lack of data on the duration of maintenance of visual gains post vitrectomy. This study thus aimed to determine the survival time of visual gains and the prognostic factors of vision loss after vitrectomy surgery for complications of proliferative diabetic retinopathy. A retrospective cohort study was conducted in an ophthalmology clinic in Malaysia. We included 134 patients with type 2 diabetes mellitus on follow-up after vitrectomy for proliferative diabetic retinopathy. Visual acuity was measured using the log of minimum angle of resolution (LogMar). A gain of ≥0.3 LogMar sustained on two subsequent visits was considered evidence of visual improvement post vitrectomy. Subjects were considered to have vision loss when their post-operative visual acuity subsequently dropped by ≥0.3 LogMar. Kaplan–Meier analysis was used to determine the survival time of visual gains. Cox Proportional Hazard regression was used to determine the prognostic factors of vision loss. The median age of patients was 56.00 years (IQR ± 10.00). The median duration of diabetes mellitus was 14.00 years (IQR ± 10.00). Approximately 50% of patients with initial improvement post vitrectomy subsequently experienced vision loss. The survival time, i.e., the median time from surgery until the number of patients with vision loss formed half of the original cohort, was 14.63 months (95% CI: 9.95, 19.32). Ischemic heart disease was a significant prognostic factor of vision loss. Patients with underlying ischemic heart disease (adjusted HR: 1.97, 95% CI: 1.18, 3.33) had a higher risk of vision loss post vitrectomy, after adjusting for other factors. Approximately half the patients with initial visual gains post vitrectomy maintained their vision for at least one year. Ischemic heart disease was a poor prognostic factor for preservation of visual gains post vitrectomy.

scholarly journals EFFECT OF MRIDWEEKADI KASHAYA SEKA IN RETINAL HAEMORRHAGES ASSOCIATED WITH NON-PROLIFERATIVE DIABETIC RETINOPATHY – A CLINICAL STUDY

2021 ◽  
pp. 1-10
Author(s):  
Navaneetha K.P ◽  
Sunil Kumar S ◽  
Kusumam Joseph
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Contrast Sensitivity ◽  
Proliferative Diabetic Retinopathy ◽  
Vision Loss ◽  
Control Sample ◽  
Modern Science ◽  
Rank Test ◽  
Fundus Photographs ◽  
Retinal Haemorrhages

Diabetic retinopathy (DR) is a leading cause of acquired vision loss in middle-aged and elderly people globally. In modern science, other than the meticulous control of diabetes there is no proven non-invasive management for the prevention or cure of Diabetic retinopathy. In this study, mild to moderate Non-proliferative diabetic retinopathy (NPDR) with retinal haemorrhages is considered as a Timira (symptomatically) and as Abhishyanda (considering etiopathogenesis) with Kapha-pitta predominance. Mridweekadi kashaya, predominantly Kapha Pitta samana, was selected for the study to be used as Seka. Method: The study design was Interventional- pre and post evaluation without control, sample size fixed as 30 eyes. Mridweekadi kashaya was used as Seka for 21 days, twice daily. Fundus photographs were taken prior to commencement of Seka, on the 22nd day and then on 30th and 60th day after completion of the procedure. Change in extent of retinal hemorrhages were assessed as visualized in Fundus photographs and direct ophthalmoscopy. Change in visual acuity was assessed by LogMar Visual acuity chart and change in contrast sensitivity by Pelli-Robson contrast sensitivity chart consecutively, prior to the treatment, on the 10th day, 22nd day and then on 30th and 60th day after completion of procedure. Statistical analysis was done using Wilcoxon signed rank test and Paired t test according to the variable. Result: Control in retinal haemorrhages associated with NPDR and improvement in visual acuity and contrast sensitivity. Conclusion: Mridweekadi kashaya seka is effective in controlling retinal haemorrhages associated with NPDR.

scholarly journals Retinal Neurodegeneration in Diabetes: an Emerging Concept in Diabetic Retinopathy

2021 ◽  
Vol 21 (12) ◽  
Author(s):  
Mira M. Sachdeva
Keyword(s):  
Diabetic Retinopathy ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Treatment Options ◽  
Retinal Disease ◽  
Vascular Pathology ◽  
Patients With Diabetes ◽  
Retinal Neurodegeneration ◽  
Diabetic Retinal Neurodegeneration

Abstract Purpose of Review Diabetic retinopathy (DR), the leading cause of blindness in working-aged adults, remains clinically defined and staged by its vascular manifestations. However, early retinal neurodegeneration may precede vascular pathology, suggesting that this neuronal damage may contribute to disease pathogenesis and represent an independent target for intervention. This review will discuss the evidence and implications for diabetic retinal neurodegeneration. Recent Findings A growing body of literature has identified progressive retinal thinning and visual dysfunction in patients with diabetes even prior to the onset of DR, though advances in retinal vascular imaging suggest that vascular remodeling and choroidal changes occur during these early stages as well. Animal models of diabetes and in vitro studies have also suggested that diabetes may directly affect the retinal neural and glial tissue, providing support to the concept that diabetic retinal neurodegeneration occurs early in the disease and suggesting potentially relevant molecular pathways. Summary Diabetic retinal neurodegeneration may represent a “preclinical” manifestation of diabetic retinal disease and remains an active area of investigation. As the natural history and molecular mechanisms become increasingly understood, it may lead to upcoming developments in not only the treatment options but also the clinical definition of DR.

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 Intravitreal Bevacizumab In Diabetic Macular Edema At RSUP Cipto Mangunkusumo in 2017

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Andi Arus Victor ◽  
Masniah Masniah ◽  
Ari Djatikusumo ◽  
Elvioza Elvioza ◽  
Gitalisa Andayani Adriono ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Intravitreal Bevacizumab ◽  
Macular Thickness ◽  
Central Macular Thickness ◽  
The Third ◽  
Department Of Ophthalmology

Introduction: Diabetic Macular Edema (DME) is a manifestation of diabetic retinopathy and is the most common cause of vision loss in diabetics. The incidence of DME has a tendency to increase, concomitant with the prevalence of diabetes globally by more than 50% from 2000 to 2030. This study aims to evaluate the proportion of central macular thickness (CMT) improvement and visual acuity in DME patients treated with intravitreal bevacizumab (IVB) injection. Methods: This study is a retrospective descriptive study. The study was conducted in the Department of Ophthalmology at RSUP Cipto Mangunkusumo (RSCM) Jakarta. Data were obtained from the medical records of all diabetic retinopathy patients with macular edema who were treated with IVB at RSCM Kirana Vitreoretina Polyclinic on January – December 2017. Results: Of the 44 subjects, improvement in best corrected visual acuity (BCVA) occurred in 24 (54.54%) subjects at the first-month evaluation and 19 (43.18%) subjects at the third-month evaluation. CMT decreased in 37 (84.41%) subjects at the first-month evaluation and 35 (81.81%) subjects at the third-month evaluation. Conclusion: Visual acuity improvement and central macular thickness reduction 3 months after IVB injection. These results strengthen IVB injection to be an alternative to adjuvant therapy in DME.   Keywords: Diabetic Macular Edema, Intravitreal Bevacizumab Injection

Proteomic Analysis of the Vitreous Body in Proliferative and Non-Proliferative Diabetic Retinopathy

2020 ◽  
Vol 17 ◽  
Author(s):  
Van-An Duong ◽  
Jeeyun Ahn ◽  
Na-Young Han ◽  
Jong-Moon Park ◽  
Jeong-Hun Mok ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Vitreous Body ◽  
Control Group ◽  
Diabetic Patients ◽  
Protein Protein Interaction ◽  
Alpha Beta ◽  
New Treatment

Background: Diabetic Retinopathy (DR), one of the major microvascular complications commonly occurring in diabetic patients, can be classified into Proliferative Diabetic Retinopathy (PDR) and Non-Proliferative Diabetic Retinopathy (NPDR). Currently available therapies are only targeted for later stages of the disease in which some pathologic changes may be irreversible. Thus, there is a need to develop new treatment options for earlier stages of DR through revealing pathological mechanisms of PDR and NPDR. Objective: The purpose of this study was to characterize proteomes of diabetic through quantitative analysis of PDR and NPDR. Methods: Vitreous body was collected from three groups: control (non-diabetes mellitus), NPDR, and PDR. Vitreous proteins were digested to peptide mixtures and analyzed using LC-MS/MS. MaxQuant was used to search against the database and statistical analyses were performed using Perseus. Gene ontology analysis, related-disease identification, and protein-protein interaction were performed using the differential expressed proteins. Results: Twenty proteins were identified as critical in PDR and NPDR. The NPDR group showed different expressions of kininogen-1, serotransferrin, ribonuclease pancreatic, osteopontin, keratin type II cytoskeletal 2 epidermal, and transthyretin. Also, prothrombin, signal transducer and activator of transcription 4, hemoglobin subunit alpha, beta, and delta were particularly up-regulated proteins for PDR group. The up-regulated proteins related to complement and coagulation cascades. Statherin was down-regulated in PDR and NPDR compared with the control group. Transthyretin was the unique protein that increased its abundance in NPDR compared with the PDR and control group. Conclusion: This study confirmed the different expressions of some proteins in PDR and NPDR. Additionally, we revealed uniquely expressed proteins of PDR and NPDR, which would be differential biomarkers: prothrombin, alpha-2-HS-glycoprotein, hemoglobin subunit alpha, beta, and transthyretin.

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