Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy.
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ABSTRACT:
SUBMITTER: Motz CT
PROVIDER: S-EPMC7306127 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This is a summary of current and emerging pharmacologic therapies utilized in the treatment of diabetic retinopathy (DR). Current therapies, such as ranibizumab, bevacizumab, triamcinolone acetonide, and fluocinolone acetonide, inhibit angiogenesis and inflammation and may be used alone or in combination with laser treatment. Emerging therapies aim to reduce oxidative stress or inhibit other signal transduction pathways, including the protein kinase C cascade and aldose reductase pathway. Future therapies may target other molecules crucial to the pathogenesis of DR, including hepatocyte growth factors and matrix metalloproteinase 9. Finally, the emergence of novel mechanisms of medication delivery may also be on the horizon.
| S-EPMC4411612 | biostudies-other
Project description:Diabetic retinopathy (DR) is the most common complication of diabetes. It causes vision loss, and the incidence is increasing with the growth of the diabetes epidemic worldwide. Over the past few decades a number of clinical trials have confirmed that careful control of glycemia and blood pressure can reduce the risk of developing DR and control its progression. In recent years, many treatment options have been developed for clinical management of the complications of DR (e.g., proliferative DR and macular edema) using laser-based therapies, intravitreal corticosteroids and anti-vascular endothelial growth factors, and vitrectomy to remove scarring and hemorrhage, but all these have limited benefits. In this review, we highlight and discuss potential molecular targets and new approaches that have shown great promise for the treatment of DR. New drugs and strategies are based on targeting a number of hyperglycemia-induced metabolic stress pathways, oxidative stress and inflammatory pathways, the renin-angiotensin system, and neurodegeneration, in addition to the use of stem cells and ribonucleic acid interference (RNAi) technologies. At present, clinical trials of some of these newer drugs in humans are yet to begin or are in early stages. Together, the new therapeutic drugs and approaches discussed may control the incidence and progression of DR with greater efficacy and safety.
| S-EPMC3659065 | biostudies-other
Project description:Purpose:To review the current therapeutic options for the management of diabetic retinopathy (DR) and diabetic macular edema (DME) and examine the evidence for integration of laser and pharmacotherapy. Methods:A review of the PubMed database was performed using the search terms diabetic retinopathy, diabetic macular edema, neovascularization, laser photocoagulation, intravitreal injection, vascular endothelial growth factor (VEGF), vitrectomy, pars plana vitreous surgery, antiangiogenic therapy. With additional cross-referencing, this yielded 835 publications of which 301 were selected based on content and relevance. Results:Many recent studies have evaluated the pharmacological, laser and surgical therapeutic strategies for the treatment and prevention of DR and DME. Several newer diagnostic systems such as optical coherence tomography (OCT), microperimetry, and multifocal electroretinography (mfERG) are also assisting in further refinements in the staging and classification of DR and DME. Pharmacological therapies for both DR and DME include both systemic and ocular agents. Systemic agents that promote intensive glycemic control, control of dyslipidemia and antagonists of the renin-angiotensin system demonstrate beneficial effects for both DR and DME. Ocular therapies include anti-VEGF agents, corticosteroids and nonsteroidal anti-inflammatory drugs. Laser therapy, both as panretinal and focal or grid applications continue to be employed in management of DR and DME. Refinements in laser devices have yielded more tissue-sparing (subthreshold) modes in which many of the benefits of conventional continuous wave (CW) lasers can be obtained without the adverse side effects. Recent attempts to lessen the burden of anti-VEGF injections by integrating laser therapy have met with mixed results. Increasingly, vitreoretinal surgical techniques are employed for less advanced stages of DR and DME. The development and use of smaller gauge instrumentation and advanced anesthesia agents have been associated with a trend toward earlier surgical intervention for diabetic retinopathy. Several novel drug delivery strategies are currently being examined with the goal of decreasing the therapeutic burden of monthly intravitreal injections. These fall into one of the five categories: non-biodegradable polymeric drug delivery systems, biodegradable polymeric drug delivery systems, nanoparticle-based drug delivery systems, ocular injection devices and with sustained release refillable devices. At present, there remains no one single strategy for the management of the particular stages of DR and DME as there are many options that have not been rigorously tested through large, randomized, controlled clinical trials. Conclusion:Pharmacotherapy, both ocular and systemic, will be the primary mode of intervention in the management of DR and DME in many cases when cost and treatment burden are less constrained. Conventional laser therapy has become a secondary intervention in these instances, but remains a first-line option when cost and treatment burden are more constrained. Results with subthreshold laser appear promising but will require more rigorous study to establish its role as adjunctive therapy. Evidence to support an optimal integration of the various treatment options is lacking. Central to the widespread adoption of any therapeutic regimen for DR and DME is substantiation of safety, efficacy, and cost-effectiveness by a body of sound clinical trials.
| S-EPMC7061411 | biostudies-literature
Project description:The aim of this study was to identify proteomic alterations associated with functional dysregulation of the retina with diabetes that could eventually be used as surrogate endpoints in preclinical drug testing studies. A multi-modal approach of antibody (Luminex)-, electrophoresis (2-DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to provide broad coverage of the retinal proteome. Transcriptional profiling through microarray analysis was also included to increase coverage and provide insight into potential regulation of protein expression changes at the mRNA level. The different technologies proved complementary, with limited coverage overlap between methods. Diabetes was induced in Sprague-Dawley male rats (Charles River Laboratories, Wilmington, MA) by intraperitoneal injection of 65 mg/kg streptozotocin (STZ) (Sigma-Aldrich, St. Louis, MO) in 10mM sodium citrate pH 4.5 vehicle. Control rats were injected with an equal dose of vehicle only. Rats had free access to food and water, and were maintained on a 12 hour light/dark cycle. Blood glucose level and body weight were measured 6 days post-STZ or vehicle injection, and biweekly throughout the experiment. Only rats with blood glucose levels >250 mg/dL at the time of the original test and throughout the experiment were included in the diabetic groups. At the time of retina harvest, rats were given a lethal dose of pentobarbital, 100 mg/kg, (Ovation Pharmaceuticals Inc., Deerfield, IL) by intraperitoneal injection and sacrificed by decapitation. Retinas were rapidly excised snap- frozen in liquid nitrogen for subsequent experimentation.
2010-06-01 | E-GEOD-20886 | biostudies-arrayexpress
Project description:Although a lot of work has been done on optical coherence tomography and color images in order to detect and quantify diseases such as diabetic retinopathy, exudates, or neovascularizations, none of them is able to evaluate the diffusion of the neovascularizations in retinas. Our work has been to develop a tool that is able to quantify a neovascularization and the fluorescein leakage during an angiography. The proposed method has been developed following a clinical trial protocol; images are taken by a Spectralis (Heidelberg Engineering). Detections are done using a supervised classification using specific features. Images and their detected neovascularizations are then spatially matched by an image registration. We compute the expansion speed of the liquid that we call diffusion index. This last one specifies the state of the disease, permits indication of the activity of neovascularizations, and allows a follow-up of patients. The method proposed in this paper has been built to be robust, even with laser impacts, to compute a diffusion index.
| S-EPMC5689132 | biostudies-literature
Project description:Diabetic retinopathy (DR) is the most common complication of diabetes. DR is characterized by damage to retinal vasculature resulting in vision impairment and, if untreated, could eventually lead to blindness. The pathogenic mechanism of DR is complex; emerging studies suggest that premature senescence of retinal cells and subsequent secretion of inflammatory cytokines exacerbate DR disease state by stimulating paracrine senescence, pathological angiogenesis, and reparative vascular regeneration. Senolytics are a new class of drugs that can selectively clear out senescent cells from the retina, thus holding a significant promise in DR treatment and prevention. In this review, we discuss the critical role of cellular senescence in DR's pathogenesis; A literature review was conducted in September of 2021 to explore the therapeutic potential of senolytics in the treatment of DR. Studies that were relevant to the research topic were selected through multiple keyword searches in the search engine, PubMed and thoroughly reviewed using abstracts and full-text articles. We present evidence from animal models for studying cellular senescence in DR and discuss multiple pathogenic mechanisms in cellular senescence and its involvement in DR. We also discuss the current state of pharmaceutical development at preclinical and clinical stages focusing on the senolytic drugs navitoclax, 17-DMAG, piperlongumine, UBX-1325, dasatinib quercetin, and fisetin. In particular, UBX-1325 holds a promising prospect for DR treatment based on the positive outcome of early clinical studies in individuals with diabetic macular edema (DME) and wet age-related macular degeneration.
| S-EPMC9462063 | biostudies-literature
Project description:BackgroundDiabetic retinopathy is a microvascular neurodegenerative disorder in diabetic patients. Peripapillary retinal nerve fiber layer changes have been described in patients with preclinical diabetic retinopathy, but study results have been inconsistent.ObjectiveTo assess changes in peripapillary retinal nerve fiber layer thickness in diabetic patients with preclinical diabetic retinopathy.MethodsA literature search was conducted through PubMed, EMBASE, Web of Science and Cochrane Library. Case-control studies on RNFL thickness in preclinical diabetic retinopathy patients and healthy controls were retrieved. A meta-analysis of weighted mean difference and a sensitivity analysis were performed using RevMan 5.2 software.ResultsThirteen case-control studies containing 668 diabetic patients and 556 healthy controls were selected. Peripapillary RNFL thickness was significantly reduced in patients with preclinical diabetic retinopathy compared to healthy controls in studies applying Optical Coherence Tomography (-2.88 ?m, 95%CI: -4.44 to -1.32, P = 0.0003) and in studies applying Scanning Laser Polarimeter (-4.21 ?m, 95%CI: -6.45 to -1.97, P = 0.0002). Reduction of RNFL thickness was significant in the superior quadrant (-3.79 ?m, 95%CI: -7.08 to -0.50, P = 0.02), the inferior quadrant (-2.99 ?m, 95%CI: -5.44 to -0.54, P = 0.02) and the nasal quadrant (-2.88 ?m, 95%CI: -4.93 to -0.82, P = 0.006), but was not significant in the temporal quadrant (-1.22 ?m, 95%CI: -3.21 to 0.76, P = 0.23), in diabetic patients.ConclusionPeripapillary RNFL thickness was significantly decreased in preclinical diabetic retinopathy patients compared to healthy control. Neurodegenerative changes due to preclinical diabetic retinopathy need more attention.
| S-EPMC4429076 | biostudies-literature
Project description:Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients and one of the main causes of acquired blindness in the world. From the 90s until date, the incidence of this complication has increased. Reactive oxygen species (ROS) is a free radical with impaired electron that usually participates in the redox mechanisms of some body molecules such as enzymes, proteins, and so on. In normal biological conditions, ROS is maintained in equilibrium, however its overproduction can lead to biological process called oxidative stress and this is considered the main pathogenesis of DR. The retina is susceptible to ROS because of high-energy demands and exposure to light. When the balance is broken, ROS produces retinal cell injury by interacting with the cellular components. This article describes the possible role of oxidative stress in the development of DR and proposes some treatment options based on its stages. The review of the topic shows that blindness caused by DR can be avoided by early detection and timely treatment.
| S-EPMC5558229 | biostudies-literature
Project description:Diabetic retinopathy (DR) accounts for ~80% of legal blindness in persons aged 20-74 years and is associated with enormous social and health burdens. Current therapies are invasive, non-curative, and in-effective in 15-25% of DR patients. This review outlines the potential utility of microRNAs (miRNAs) as biomarkers and potential therapy for diabetic retinopathy. miRNAs are small noncoding forms of RNA that may play a role in the pathogenesis of DR by altering the level of expression of genes via single nucleotide polymorphism and regulatory loops. A majority of miRNAs are intracellular and specific intracellular microRNAs have been associated with cellular changes associated with DR. Some microRNAs are extracellular and called circulatory microRNAs. Circulatory miRNAs have been found to be differentially expressed in serum and bodily fluid in patients with diabetes mellitus (DM) with and without retinopathy. Some miRNAs have been associated with the severity of DR, and future studies may reveal whether circulatory miRNAs could serve as novel reliable biomarkers to detect or predict retinopathy progression. Therapeutic strategies can be developed utilizing the natural miRNA/long noncoding RNA (lncRNA) regulatory loops. miRNAs and lncRNAs are two major families of the non-protein-coding transcripts. They are regulatory molecules for fundamental cellular processes via a variety of mechanisms, and their expression and function are tightly regulated. The recent evidence indicates a cross-talk between miRNAs and lncRNAs. Therefore, dysregulation of miRNAs and lncRNAs is critical to human disease pathogenesis, such as diabetic retinopathy. miRNAs are long-distance communicators and reprogramming agents, and they embody an entirely novel paradigm in cellular and tissue signaling and interaction. By targeting specific miRNAs, whole pathways implicated in the pathogenesis of DR may potentially be altered. Understanding the endogenous roles of miRNAs in the pathogenesis of diabetic retinopathy could lead to novel diagnostic and therapeutic approaches to managing this frequently blinding retinal condition.
| S-EPMC8421969 | biostudies-literature
Project description:ObjectiveParaoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the level of vitreous has not been investigated.Research design and methodsUndiluted vitreous from patients with proliferative diabetic retinopathy (PDR) (n = 13) and macular hole (MH) (n = 8) was used to determine PON-HCTLase and PON-AREase activity spectrophotometrically. HCTL levels were detected by liquid chromatography-tandem mass spectrometry. In vitro studies were done in primary cultures of bovine retinal capillary endothelial cells (BRECs) to determine the dose- and time-dependent effect of HCTL and homocysteine (Hcys) on PON-HCTLase activity, as well as to determine mRNA expression of PON by RT-PCR.ResultsA significant increase in HCTL and PON-HCTLase activity was observed in PDR compared with MH (P = 0.036, P = 0.001), with a significant positive correlation between them (r = 0.77, P = 0.03). The in vitro studies on BRECs showed a dose- and time-dependent increase in the PON-HCTLase activity and mRNA expression of PON2 when exposed to HCTL and Hcys.ConclusionsThis is the first study showing elevated levels of vitreous HCTL and PON-HCTLase activity in PDR. These elevations are probably a protective effect to eliminate HCTL, which mediates endothelial cell dysfunction. Thus, vitreous levels of HCTL and PON activity can be markers of diabetic retinopathy. The bioinformatics analysis reveals that the structure and function of PON that can be modulated by hyperhomocysteinemia in PDR can affect the dual-enzyme activity of PON.
| S-EPMC2928358 | biostudies-literature