scholarly journals ROCK as a Therapeutic Target of Diabetic Retinopathy

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Ryoichi Arita ◽  
Yasuaki Hata ◽  
Tatsuro Ishibashi
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Ocular Complication ◽  
Working Population ◽  
Critical Problem ◽  
Rock Inhibitor ◽  
Severe Vision Loss ◽  
Pharmacologic Treatments ◽  
Late Stages

The increasing global prevalence of diabetes is a critical problem for public health. In particular, diabetic retinopathy, a prevalent ocular complication of diabetes mellitus, causes severe vision loss in working population. A better understanding of the pathogenesis and the development of new pharmacologic treatments are needed. This paper describes the relevance between Rho/ROCK pathway and the pathogenesis of diabetic retinopathy from its early to late stages. Moreover, the therapeutic potential of ROCK inhibitor in the total management of diabetic retinopathy is discussed.

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 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.

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 A Survey: Deep Learning Methods on Diabetic Retinopathy

2021 ◽  
pp. 131-135
Author(s):  
Kamlesh Raghuwanshi ◽  
Vipin Tiwari
Keyword(s):  
Diabetic Retinopathy ◽  
Deep Learning ◽  
Vision Loss ◽  
The Body ◽  
Fundus Images ◽  
Learning Approaches ◽  
Severe Vision Loss ◽  
Pros And Cons ◽  
Retinal Fundus ◽  
Aided Diagnosis

Diabetes Mellitus (DM) is a metabolic condition that arises because of the elevated level of blood sugar in the body which triggers eye deficiency, also known as Diabetic Retinopathy (DR) which causes severe vision loss. An effective and efficient tool for early DR diagnosis and assisting experts is a computer-aided diagnosis (CAD) device focused on retinal fundus images that can detect this problem. A CAD method requires different phases in fundus images, such as identification, segmentation and lesion classification. Recent advancement of deep learning (DL) and its definitive victory over conventional ML approaches inspired researchers for implementation of many deep-learning-based techniques using different phases of fundus images. This paper highlights these deep learning approaches along with their pros and cons.

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

scholarly journals Visual Cortex Transcranial Direct Current Stimulation for Proliferative Diabetic Retinopathy Patients: A Double-Blinded Randomized Exploratory Trial

2021 ◽  
Vol 11 (2) ◽  
pp. 270
Author(s):  
Angelito Braulio F. de Venecia ◽  
Shane M. Fresnoza
Keyword(s):  
Diabetic Retinopathy ◽  
Visual Cortex ◽  
Proliferative Diabetic Retinopathy ◽  
Direct Current ◽  
Transcranial Direct Current Stimulation ◽  
Vision Loss ◽  
Sham Stimulation ◽  
Direct Current Stimulation ◽  
Residual Vision ◽  
Cathodal Tdcs

Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes. PDR-related retinal hemorrhages often lead to severe vision loss. The main goals of management are to prevent visual impairment progression and improve residual vision. We explored the potential of transcranial direct current stimulation (tDCS) to enhance residual vision. tDCS applied to the primary visual cortex (V1) may improve visual input processing from PDR patients’ retinas. Eleven PDR patients received cathodal tDCS stimulation of V1 (1 mA for 10 min), and another eleven patients received sham stimulation (1 mA for 30 s). Visual acuity (logarithm of the minimum angle of resolution (LogMAR) scores) and number acuity (reaction times (RTs) and accuracy rates (ARs)) were measured before and immediately after stimulation. The LogMAR scores and the RTs of patients who received cathodal tDCS decreased significantly after stimulation. Cathodal tDCS has no significant effect on ARs. There were no significant changes in the LogMAR scores, RTs, and ARs of PDR patients who received sham stimulation. The results are compatible with our proposal that neuronal noise aggravates impaired visual function in PDR. The therapeutic effect indicates the potential of tDCS as a safe and effective vision rehabilitation tool for PDR patients.

scholarly journals Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donato Santovito ◽  
Lisa Toto ◽  
Velia De Nardis ◽  
Pamela Marcantonio ◽  
Rossella D’Aloisio ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
External Validation ◽  
Diabetic Patients ◽  
Disease Biomarkers ◽  
Response To Stress ◽  
Severity Of The Disease ◽  
Plasma Microrna

AbstractDiabetic retinopathy (DR) is a leading cause of vision loss and disability. Effective management of DR depends on prompt treatment and would benefit from biomarkers for screening and pre-symptomatic detection of retinopathy in diabetic patients. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression which are released in the bloodstream and may serve as biomarkers. Little is known on circulating miRNAs in patients with type 2 diabetes (T2DM) and DR. Here we show that DR is associated with higher circulating miR-25-3p (P = 0.004) and miR-320b (P = 0.011) and lower levels of miR-495-3p (P < 0.001) in a cohort of patients with T2DM with DR (n = 20), compared with diabetic subjects without DR (n = 10) and healthy individuals (n = 10). These associations persisted significant after adjustment for age, gender, and HbA1c. The circulating levels of these miRNAs correlated with severity of the disease and their concomitant evaluation showed high accuracy for identifying DR (AUROC = 0.93; P < 0.001). Gene ontology analysis of validated targets revealed enrichment in pathways such as regulation of metabolic process (P = 1.5 × 10–20), of cell response to stress (P = 1.9 × 10–14), and development of blood vessels (P = 2.7 × 10–14). Pending external validation, we anticipate that these miRNAs may serve as putative disease biomarkers and highlight novel molecular targets for improving care of patients with diabetic retinopathy.

scholarly journals The Positive Legacy of Vision Loss: Pathways to Posttraumatic Growth

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 616-617
Author(s):  
Corinna Tanner ◽  
Michael Caserta ◽  
Jia-Wen Guo ◽  
Margaret Clayton ◽  
Paul Bernstein ◽  
...  
Keyword(s):  
Posttraumatic Growth ◽  
Cognitive Processing ◽  
Mixed Method ◽  
Vision Loss ◽  
Social Issues ◽  
Qualitative Interviews ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Severe Vision Loss ◽  
Age Range

Abstract This mixed method study describes posttraumatic growth (PTG) accruing form experience with vision loss caused by severe age related macular degeneration (AMD) and explores relationships between depression, social support, and cognitive processing, on the path to PTG. Research describing the psychological and social issues surrounding AMD has focused on negative outcomes. However, learning from highly challenging experiences, such as vision loss, can offer benefits. In this study, these included an increased sense of personal strength, increased spirituality, and empathy for others (all domains of PTG). 89 participants with severe vision loss (mean age = 85.3 years, age range = 74–98 years) completed the interviewer-administered composite questionnaire, which identified elements of Tedeschi and Calhoun’s model of PTG. Relationships between variables were examined using path analysis. Findings were contextualized with data from 15 qualitative interviews. Findings underscored the importance of supportive others and deliberate cognitive processing in the path to PTG.

An Explainable Deep Learning Ensemble Model for Robust Diagnosis of Diabetic Retinopathy Grading

2021 ◽  
Vol 17 (3s) ◽  
pp. 1-24
Author(s):  
Mohammad Shorfuzzaman ◽  
M. Shamim Hossain ◽  
Abdulmotaleb El Saddik
Keyword(s):  
Diabetic Retinopathy ◽  
Deep Learning ◽  
Vision Loss ◽  
Final Diagnosis ◽  
Learning Rate ◽  
Ensemble Model ◽  
Fundus Images ◽  
Robust Detection ◽  
Retinal Fundus Images ◽  
Retinal Fundus

Diabetic retinopathy (DR) is one of the most common causes of vision loss in people who have diabetes for a prolonged period. Convolutional neural networks (CNNs) have become increasingly popular for computer-aided DR diagnosis using retinal fundus images. While these CNNs are highly reliable, their lack of sufficient explainability prevents them from being widely used in medical practice. In this article, we propose a novel explainable deep learning ensemble model where weights from different models are fused into a single model to extract salient features from various retinal lesions found on fundus images. The extracted features are then fed to a custom classifier for the final diagnosis of DR severity level. The model is trained on an APTOS dataset containing retinal fundus images of various DR grades using a cyclical learning rates strategy with an automatic learning rate finder for decaying the learning rate to improve model accuracy. We develop an explainability approach by leveraging gradient-weighted class activation mapping and shapely adaptive explanations to highlight the areas of fundus images that are most indicative of different DR stages. This allows ophthalmologists to view our model's decision in a way that they can understand. Evaluation results using three different datasets (APTOS, MESSIDOR, IDRiD) show the effectiveness of our model, achieving superior classification rates with a high degree of precision (0.970), sensitivity (0.980), and AUC (0.978). We believe that the proposed model, which jointly offers state-of-the-art diagnosis performance and explainability, will address the black-box nature of deep CNN models in robust detection of DR grading.

Beyond vision loss: the independent impact of diabetic retinopathy on vision-related quality of life in a Chinese Singaporean population

2018 ◽  
Vol 103 (9) ◽  
pp. 1314-1319 ◽  
Author(s):  
Eva K Fenwick ◽  
Ryan E K Man ◽  
Alfred Tau Liang Gan ◽  
Neelam Kumari ◽  
Charlene Wong ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Well Being ◽  
Linear Regression Models ◽  
Cross Sectional ◽  
Significant Difference ◽  
Related Quality ◽  
The Impact

Background/aimsTo assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population.MethodsThe Singapore Chinese Eye Study (n=3353; 2009–2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the ‘Reading’, ‘Mobility’ and ‘Emotional’ domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models.ResultsOf the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR.ConclusionsWe documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR.

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