Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined ...as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working‐age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti‐vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.
•Degraded miR-17-3p and raised STAT1 is found in retinal tissues.•Increased miR-17-3p suppressed inflammatory reaction of DR mice.•Elevated exosomal miR-17-3p suppressed antioxidant injury of DR ...mice.•4 There is a target relationship between STAT1 and miR-17-3p.•This study is essential for finding new targets for DR.
Accumulating evidence has reported the role of microRNA (miR) on diabetic retinopathy (DR). Thus, the aim of the study was to investigate the effect of exosomal miR-17-3p targeting signal transducer and activator of transcription 1 (STAT1) on inflammatory reaction and antioxidant injury of DR mice.
A mouse diabetes model was established and injected with miR-17-3p-containing human umbilical cord mesenchymal stem cells (hucMSCs)-derived exosomes to ascertain the role of exosomal miR-17-3p. The blood glucose, glycosylated hemoglobin (HbAlc), weight, hemoglobin (Hb) content, inflammatory factors, oxidative stress factors, vascular endothelial growth factor (VEGF), apoptosis index and glutamine synthetase (GS) level in serum and/or retinal tissues of DR mice were measured. miR-17-3p and STAT1 expression in retinal tissues as well as the target relationship between miR-17-3p and STAT1 were tested.
miR-17-3p decreased and STAT1 increased in retinal tissues of DR mice, and STAT1 was the target gene of miR-17-3p. Injection of up-regulated exosomal miR-17-3p reduced the blood glucose and HbAlc, increased the weight, Hb content and GS level, decreased contents of inflammatory factors and VEGF, alleviated oxidative injury, and inhibited retinal cell apoptosis in DR mice through inhibiting STAT1.
Functional studies reveal that hucMSCs-derived exosomes shuffle miR-17-3p to ameliorate inflammatory reaction and oxidative injury of DR mice via targeting STAT1.
Summary Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a ...third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising.
Purpose
To increase the efficiency of retinal image grading, algorithms for automated grading have been developed, such as the IDx‐DR 2.0 device. We aimed to determine the ability of this device, ...incorporated in clinical work flow, to detect retinopathy in persons with type 2 diabetes.
Methods
Retinal images of persons treated by the Hoorn Diabetes Care System (DCS) were graded by the IDx‐DR device and independently by three retinal specialists using the International Clinical Diabetic Retinopathy severity scale (ICDR) and EURODIAB criteria. Agreement between specialists was calculated. Results of the IDx‐DR device and experts were compared using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), distinguishing between referable diabetic retinopathy (RDR) and vision‐threatening retinopathy (VTDR). Area under the receiver operating characteristic curve (AUC) was calculated.
Results
Of the included 1415 persons, 898 (63.5%) had images of sufficient quality according to the experts and the IDx‐DR device. Referable diabetic retinopathy (RDR) was diagnosed in 22 persons (2.4%) using EURODIAB and 73 persons (8.1%) using ICDR classification. Specific intergrader agreement ranged from 40% to 61%. Sensitivity, specificity, PPV and NPV of IDx‐DR to detect RDR were 91% (95% CI: 0.69–0.98), 84% (95% CI: 0.81–0.86), 12% (95% CI: 0.08–0.18) and 100% (95% CI: 0.99–1.00; EURODIAB) and 68% (95% CI: 0.56–0.79), 86% (95% CI: 0.84–0.88), 30% (95% CI: 0.24–0.38) and 97% (95% CI: 0.95–0.98; ICDR). The AUC was 0.94 (95% CI: 0.88–1.00; EURODIAB) and 0.87 (95% CI: 0.83–0.92; ICDR). For detection of VTDR, sensitivity was lower and specificity was higher compared to RDR. AUC's were comparable.
Conclusion
Automated grading using the IDx‐DR device for RDR detection is a valid method and can be used in primary care, decreasing the demand on ophthalmologists.
•Rat diabetic retinopathy was associated was upregulated TLR4/NFκB expression.•Retinal glutamate and cytokine levels were elevated.•Metformin enhanced the retinal histopathological picture and ...ultrastructures.•Metformin downregulated TNF-α, VEGF andTLR4/NFκB expression.•Metformin reduced retinal glutamate level.
Microvascular complications of diabetes mellitus are progressively significant reasons for mortality. Metformin (MET) is considered as the first-line therapy for type 2 diabetes patients, and may be especially beneficial in cases of diabetic retinopathy although the precise mechanisms of MET action are not fully elucidated. The current study was designed to inspect the antioxidant and modulatory actions of MET on DRET in streptozotocin-induced diabetic rats. The effect of MET on the toll-like receptor 4/nuclear factor kappa B (TLR4/NFkB), inflammatory burden and glutamate excitotoxicity was assessed. Twenty-four male rats were assigned to four experimental groups: (1) Vehicle group, (2) Diabetic control: developed diabetes by injection of streptozotocin (60 mg/kg, i.p.). (3&4) Diabetic + MET group: diabetic rats were left for 9 weeks without treatment and then received oral MET 100 and 200 mg/kg for 6 weeks. Retinal samples were utilized in biochemical, histological, immunohistochemical and electron microscopic studies. MET administration significantly decreased retinal level of insulin growth factor and significantly suppressed the diabetic induced increase of malondialdehyde, glutamate, tumor necrosis factor-α and vascular endothelial growth factor (VEGF). Further, MET decreased the retinal mRNA expression of NFkB, tumor necrosis factor-α and TLR4 in diabetic rats. The current findings shed the light on MET’s efficacy as an adjuvant therapy to hinder the development of diabetic retinopathy, at least partly, via inhibition of oxidative stress-induced NFkB/TLR4 pathway and suppression of glutamate excitotoxicity.
Diabetic retinopathy (DR) impairs vision of patients with type 1 and type 2 diabetes, associated with vascular dysfunction and occlusion, retinal edema, hemorrhage, and inappropriate growth of new ...blood vessels. The recent success of biologic treatments targeting vascular endothelial growth factor (VEGF) demonstrates that treating the vascular aspects in the later stages of the disease can preserve vision in many patients. It would also be highly desirable to prevent the onset of the disease or arrest its progression at a stage preceding the appearance of overt microvascular pathologies. The progression of DR is not necessarily linear but may follow a series of steps that evolve over the course of multiple years. Abundant data suggest that diabetes affects the entire neurovascular unit of the retina, with an early loss of neurovascular coupling, gradual neurodegeneration, gliosis, and neuroinflammation occurring before observable vascular pathologies. In this article, we consider the pathology of DR from the point of view that diabetes causes measurable dysfunctions in the complex integral network of cell types that produce and maintain human vision.
A Review on Diabetic Retinopathy Kour, Vijender; Swain, Jayshree; Singh, Jaspreet ...
Current diabetes reviews,
01/2024, Volume:
20, Issue:
6
Journal Article
Peer reviewed
Diabetic retinopathy is a well-recognised microvascular complication of diabetes and is among the leading cause of blindness all over the world. Over the last decade, there have been advances in the ...diagnosis of diabetic retinopathy and diabetic macular edema. At the same time, newer therapies for the management of diabetic retinopathy have evolved. As a result of these advances, a decline in severe vision loss due to diabetes has been witnessed in some developing countries. However, there is a steady increase in the number of people affected with diabetes, and is expected to rise further in the coming years. Therefore, it is prudent to identify diabetic retinopathy, and timely intervention is needed to decrease the burden of severe vision loss. An effort has been made to review all the existing knowledge regarding diabetic retinopathy in this article and summarize the present treatment options for diabetic retinopathy.
Diabetic retinopathy Wong, Tien Y; Cheung, Chui Ming Gemmy; Larsen, Michael ...
Nature reviews. Disease primers,
03/2016, Volume:
2
Journal Article
Peer reviewed
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and is a major cause of vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. Severe stages ...of DR include proliferative DR, caused by the abnormal growth of new retinal blood vessels, and diabetic macular oedema, in which there is exudation and oedema in the central part of the retina. DR is strongly associated with a prolonged duration of diabetes, hyperglycaemia and hypertension. It is traditionally regarded as a microvascular disease, but retinal neurodegeneration is also involved. Complex interrelated pathophysiological mechanisms triggered by hyperglycaemia underlie the development of DR. These mechanisms include genetic and epigenetic factors, increased production of free radicals, advanced glycosylation end products, inflammatory factors and vascular endothelial growth factor (VEGF). Optimal control of blood glucose and blood pressure in individuals with diabetes remains the cornerstone for preventing the development and arresting the progression of DR. Anti-VEGF therapy is currently indicated for diabetic macular oedema associated with vision loss, whereas laser photocoagulation prevents severe vision loss in eyes with proliferative DR. These measures, together with increasing public awareness and access to regular screening for DR with retinal photography, and the development of new treatments to address early disease stages, will lead to better outcomes and prevent blindness for patients with DR.
Aims
To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme.
Materials and methods
The SUSTAIN clinical trial programme evaluated the efficacy and safety of ...semaglutide, a glucagon‐like peptide‐1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2‐year, pre‐approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at‐risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage‐points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC.
Results
There was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre‐existing DR and poor glycaemic control at baseline, and who were treated with insulin.
Conclusions
Early worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide.
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