scholarly journals Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

2021 ◽  
Vol 1 (3) ◽  
pp. 306-322
Author(s):  
Tatiana Borodina ◽  
Dmitry Kostyushev ◽  
Andrey A. Zamyatnin ◽  
Alessandro Parodi

The incidence of diabetes and the pathological conditions associated with chronic hyperglycemia is increasing worldwide. Among them, diabetic retinopathy represents a leading cause of vision loss, causing a significant structural and functional impairment of the retinal and choroidal capillary network. Current therapies include anti-angiogenic and anti-inflammatory drugs administered through repetitive and invasive intraocular injections, and associated with significant adverse effects. The presence of ocular barriers affects the efficiency of topically administered therapeutics for treating the posterior segment of the eye. In this scenario, nanomedicine could improve current therapies for diabetic retinopathy by providing tools that can decrease the number of injections thanks to their controlled release properties, while some materials showed a natural ability to mitigate pathological neo-angiogenesis. Moreover, specific surface modifications could open new scenarios for the development of topical treatments. This review describes current advances in generating nanomedicine for diabetic retinopathy, focusing on the properties of the different materials tested explicitly for this purpose.

2021 ◽  
Vol 3 (2) ◽  
pp. 66-74
Author(s):  
Naufallah Dinda Harumi ◽  
Ramzi Amin

Abstract Introduction.Diabetic retinopathy is a progressive microangiopathy characterized by damage and occlusion of small blood vessels. The earliest pathologic changes are thickening of the capillary endothelial basement membrane and a reduction in the number of pericits. Diabetic retinopathy is the main cause of vision loss in type 1 of DM patients and has various risk factors such as chronic hyperglycemia, hypertension, hypercholesterolemia, and elevated HbA1C levels. Methods.This research was conducted using a descriptive observational analytic method with a cross sectional approach at The Eye Polyclinic (RSUP) Dr. Mohammad Hoesin Palembang used secondary data on diabetic retinopathy patients. The sample consisted of 64 patients with a total sampling technique, there were 50 patients who met the inclusion criteria. Results.There was a significant relationship between HbA1C levels (p value = 0.050) with a PR value = 1.463 and total cholesterol (p value = 0.038) with a PR value = 1.667 for diabetic retinopathy. Conclusion.HbA1C levels and total cholesterol are significant risk factors for diabetic retinopathy.


2021 ◽  
Vol 10 (20) ◽  
pp. 1463-1468
Author(s):  
Abhinav Ashok Agrawal ◽  
Niharika Krishna Shetty

BACKGROUND Diabetic retinopathy (DR) is reported to be the leading cause of vision loss in adults aged between 20–74 years. Early detection and prompt evaluation is essential to prevent the blindness related to diabetes. Simple and quick out-patient department (OPD) tests are essential for early detection of maculopathy in diabetes, which will enhance the treatment and rehabilitation. The purpose of this study was to evaluate the correlation of photo stress test and Amsler’s grid test with diabetic retinopathy and maculopathy. We also wanted to study the variation in photo stress test and the patterns of visual disturbances using Amsler grid in different stages of diabetic retinopathy. METHODS All patients with type 2 diabetes were included for a study duration of one year. A cross sectional study design was planned. Anterior and posterior segment evaluation was done. Photo stress test was performed with a torch light and the recovery time was recorded. Amsler grid was performed on each patient at 33 cm distance. The results were recorded in terms of micropsia, macropsia, metamorphopsia, and any other ill-defined scotomas. The posterior segment, in terms of vitreous and retina was evaluated with 20 D lens on an indirect ophthalmoscopy and the macular details were evaluated on a 90 D lens with slit lamp biomicroscopy. Early Treatment Diabetic Retinopathy (ETDR) classification was used for classifying the retinopathy and the maculopathy stage in patients. RESULTS There was a correlation between paroxysmal supraventricular tachycardia (PST) and the stage of diabetic retinopathy; between PST and diabetic maculopathy; with increasing severity of diabetic retinopathy and maculopathy associated with higher or prolonged PST values. No correlation was found between Amsler’s grid and DR staging. CONCLUSIONS PST can be used to assess severity of diabetic retinopathy in a pre-clinical and early clinical stage in places where access to the equipment for posterior segment evaluation is unavailable. Amsler’s grid evaluation did not have a role in evaluation of macula in cases of diabetic retinopathy. KEY WORDS Macula, Amsler, Photostress Test, Metamorphopsia


2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Cristina Hernández ◽  
Massimo Dal Monte ◽  
Rafael Simó ◽  
Giovanni Casini

Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.


2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Abbott L. Willard ◽  
Ira M. Herman

Diabetic retinal complications, including macular edema (DME) and proliferative diabetic retinopathy (PDR), are the leading cause of new cases of blindness among adults aged 20–74. Chronic hyperglycemia, considered the underlying cause of diabetic retinopathy, is thought to act first through violation of the pericyte-endothelial coupling. Disruption of microvascular integrity leads to pathologic consequences including hypoxia-induced imbalance in vascular endothelial growth factor (VEGF) signaling. Several anti-VEGF medications are in clinical trials for use in arresting retinal angiogenesis arising from DME and PDR. Although a review of current clinical trials shows promising results, the lack of large prospective studies, head-to-head therapeutic comparisons, and potential long-term and systemic adverse events give cause for optimistic caution. Alternative therapies including targeting pathogenic specific angiogenesis and mural-cell-based therapeutics may offer innovative solutions for currently intractable clinical problems. This paper describes the mechanisms behind diabetic retinal complications, current research supporting anti-VEGF medications, and future therapeutic directions.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  

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.


2021 ◽  
Vol 11 (2) ◽  
pp. 270
Author(s):  
Angelito Braulio F. de Venecia ◽  
Shane M. Fresnoza

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.


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 ◽  
...  

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donato Santovito ◽  
Lisa Toto ◽  
Velia De Nardis ◽  
Pamela Marcantonio ◽  
Rossella D’Aloisio ◽  
...  

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.


Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2441
Author(s):  
Drake W. Lem ◽  
Dennis L. Gierhart ◽  
Pinakin Gunvant Davey

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.


Author(s):  
Mohammad Shorfuzzaman ◽  
M. Shamim Hossain ◽  
Abdulmotaleb El Saddik

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.


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