Correction to: Beneficial effects of the nutritional supplements on the development of diabetic retinopathy

The main goals of this work were to assess whether the topical administration of glucagon-like peptide-1 (GLP-1) could revert the impairment of the neurovascular unit induced by long-term diabetes (24 weeks) in diabetic mice and to look into the underlying mechanisms. For that reason, db/db mice were treated with eye drops of GLP-1 or vehicle for 3 weeks. Moreover, db/+ mice were used as control. Studies performed in vivo included electroretinogramand the assessment of vascular leakage by using Evans Blue. NF-κB, GFAP and Ki67 proteins were analyzed by immunofluorescence (IF). Additionally, caspase 9, AMPK, IKBα, NF-κB, AKT, GSK3, β-catenin, Bcl-xl, and VEGF were analyzed by WB. Finally, VEGF, IL-1β, IL-6, TNF-α, IL-18, and NLRP3 were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence. We found that topical administration of GLP-1 reverted reactive gliosis and albumin extravasation, and protected against apoptosis and retinal dysfunction. Regarding the involved mechanisms, GLP-1 exerted an anti-inflammatory action by decreasing NF-κB, inflammosome, and pro-inflammatory factors. In addition, it also decreased VEGF expression. Furthermore, GLP-1 promoted cell survival by increasing the anti-apoptotic protein Bcl-xl and the signaling pathway Akt/GSK3b/β-catenin. Finally, Ki67 results revealed that GLP-1 treatment could induce neurogenesis. In conclusion, the topical administration of GLP-1 reverts the impairment of the neurovascular unit by modulating essential pathways involved in the development of diabetic retinopathy (DR). These beneficial effects on the neurovascular unit could pave the way for clinical trials addressed to confirm the effectiveness of GLP-1 in early stages of DR.

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Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

Cells ◽

10.3390/cells8030213 ◽

2019 ◽

Vol 8 (3) ◽

pp. 213 ◽

Cited By ~ 15

Author(s):

Ping Zhou ◽

Weijie Xie ◽

Xiangbao Meng ◽

Yadong Zhai ◽

Xi Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Oral Treatment ◽

Müller Cells ◽

Panax Notoginseng ◽

Protective Effects ◽

Muller Cells ◽

Beneficial Effects ◽

Pre Treatment ◽

Lc3 Puncta

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

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Role of Oxidative Stress in Diabetic Retinopathy and the Beneficial Effects of Flavonoids

Current Pharmaceutical Design ◽

10.2174/1381612824666180515151043 ◽

2018 ◽

Vol 24 (19) ◽

pp. 2180-2187 ◽

Cited By ~ 7

Author(s):

Mohammad Shamsul Ola ◽

Dalia Al-Dosari ◽

Abdullah S. Alhomida

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Experimental Studies ◽

Developed Countries ◽

Retinal Damage ◽

Beneficial Effects ◽

Diabetic Retina ◽

Retinal Pathology ◽

Dietary Flavonoids

Diabetic Retinopathy (DR) is one of the leading causes of decreased vision and blindness in developed countries. Diabetes-induced metabolic disorder is believed to increase oxidative stress in the retina. This results in deleterious change through dysregulation of cellular physiology that damages both neuronal and vascular cells. In this review, we first highlight the evidence of potential metabolic sources and pathways which increase oxidative stress that contribute to retinal pathology in diabetes. As oxidative stress is a central factor in the pathophysiology of DR, antioxidants therapy would be beneficial towards preventing the retinal damage. A number of experimental studies by our group and others showed that dietary flavonoids cause reduction in increased oxidative stress and other beneficial effects in diabetic retina. We then discuss the beneficial effects of the six major flavonoid families, such as flavanones, flavanols, flavonols, isoflavones, flavones and anthocyanins, which have been studied to improve retinal damage. Flavanoids, being known antioxidants, may ameliorate the retinal degenerative factors including apoptosis, inflammation and neurodegeneration in diabetes. Therefore, intake of potential dietary flavonoids would limit oxidative stress and thereby prevent the retinal damage, and subsequently the development of DR.

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2064 Regulation of retinal protein O-GlcNAcylation by angiotensin-(1-7) and cAMP

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.114 ◽

2018 ◽

Vol 2 (S1) ◽

pp. 25-25

Author(s):

Sadie Dierschke ◽

Amy Arnold ◽

Michael M. Dennis

Keyword(s):

Diabetic Retinopathy ◽

High Fat Diet ◽

Renin Angiotensin System ◽

High Fat ◽

Retinal Protein ◽

Beneficial Effects ◽

Camp Analog ◽

Study Population ◽

Ras Blockers ◽

The Impact

OBJECTIVES/SPECIFIC AIMS: Increased retinal protein O-GlcNAcylation occurs in response to hyperglycemia and contributes to diabetic retinopathy. Renin-angiotensin system (RAS) blockers reduce the incidence of diabetic retinopathy. Beneficial effects of RAS blockers are often attributed to production of angiotensin-(1-7) (Ang1-7). The objective here is to determine the impact of Ang1-7 on retinal protein O-GlcNAcylation. METHODS/STUDY POPULATION: C57/BL6 mice were fed a high-fat diet for 8 weeks and then treated for 3 weeks with either a vehicle control, the RAS blocker captopril, or captopril and the Ang1-7 receptor antagonist A779. R28 cells were used to assess levels of O-GlcNAcylated proteins in response to Ang1-7, and the role of cAMP was investigated with addition of forskolin, 6-Bnz-cAMP-AM, and 8-pCPT-2-O-Me-cAMP-AM to cell culture medium. RESULTS/ANTICIPATED RESULTS: Captopril attenuated retinal protein O-GlcNAcylation in mice fed a high-fat diet. This effect was reversed by A779. Ang1-7 attenuated protein O-GlcNAcylation and increased cAMP levels. Forskolin and the EPAC selective cAMP analog 8-pCPT-2-O-Me-cAMP-AM, but not the PKA selective cAMP analog 6-Bnz-cAMP-AM, attenuated O-GlcNAcylation. Inhibiting EPAC blocked the effect of forskolin, whereas inhibiting PKA did not. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates a novel role for Ang1-7 in the retina and identifies a potential EPAC-dependent mechanism that regulates protein O-GlcNAcylation. Thus, future therapeutics targeted at an Ang1-7/EPAC axis in retina may be used to address DR.

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Medical management of diabetic retinopathy

Diabetic Retinopathy: Screening to Treatment (Oxford Diabetes Library) ◽

10.1093/med/9780198834458.003.0016 ◽

2020 ◽

pp. 145-156

Author(s):

Paul M. Dodson

Keyword(s):

Diabetic Retinopathy ◽

Cardiovascular Risk ◽

Medical Management ◽

Receptor Blockade ◽

Angiotensin Receptor ◽

Risk Factor Management ◽

Beneficial Effects ◽

Standard Management ◽

Multiple Cardiovascular Risk Factor ◽

Angiotensin Receptor Blockade

Medical management is focused on the proven benefit of tight glucose and blood pressure (BP) control. Standard management includes multiple cardiovascular risk factor management with angiotensin receptor blockade, statin, and fibrate treatment. Targets to achieve include HbA1c <7% (53 mmol/mol), BP <140/80, and serum cholesterol <4 mmol/L. A number of large recent trials have specifically demonstrated the beneficial effects on diabetic retinopathy (DR) of angiotensin receptor blockade (the DIRECT study) and fenofibrate (the fenofibrate intervention and event lowering in diabetes [FIELD] and action to control cardiovascular risk in diabetes [ACCORD] eye studies).

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Botanical Compounds: Effects on Major Eye Diseases

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/549174 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 21

Author(s):

Tuan-Phat Huynh ◽

Shivani N. Mann ◽

Nawajes A. Mandal

Keyword(s):

Diabetic Retinopathy ◽

Animal Models ◽

Retinitis Pigmentosa ◽

Cell Cultures ◽

Clinical Studies ◽

Eye Diseases ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Beneficial Effects ◽

Age Related

Botanical compounds have been widely used throughout history as cures for various diseases and ailments. Many of these compounds exhibit strong antioxidative, anti-inflammatory, and antiapoptotic properties. These are also common damaging mechanisms apparent in several ocular diseases, including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy, cataract, and retinitis pigmentosa. In recent years, there have been many epidemiological and clinical studies that have demonstrated the beneficial effects of plant-derived compounds, such as curcumin, lutein and zeaxanthin, danshen, ginseng, and many more, on these ocular pathologies. Studies in cell cultures and animal models showed promising results for their uses in eye diseases. While there are many apparent significant correlations, further investigation is needed to uncover the mechanistic pathways of these botanical compounds in order to reach widespread pharmaceutical use and provide noninvasive alternatives for prevention and treatments of the major eye diseases.

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The Potential Beneficial Effects of Curcumin in Diabetic Retinopathy

Curcumin for Neurological and Psychiatric Disorders ◽

10.1016/b978-0-12-815461-8.00022-0 ◽

2019 ◽

pp. 401-417

Author(s):

Mohd Imtiaz Nawaz ◽

Abdullah S. Alhomida ◽

Mohammad Shamsul Ola

Keyword(s):

Diabetic Retinopathy ◽

Beneficial Effects

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Yiqi Yangyin Huoxue Method in Treating Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6020846 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Chen Ou ◽

Yi Jing Yang ◽

Qing Hua Peng

Keyword(s):

Diabetic Retinopathy ◽

Methodological Quality ◽

Controlled Trial ◽

Meta Analysis ◽

Knowledge Network ◽

Fluorescence Angiography ◽

Cochrane Library ◽

Assessment Data ◽

Beneficial Effects ◽

Randomized Controlled

Objective. To evaluate the efficacy of Yiqi Yangyin Huoxue method in the treatment of diabetic retinopathy (DR) with meta-analysis. Method. A randomized controlled trial of Yiqi Yangyin Huoxue method in the treatment of diabetic retinopathy in PubMed, Medline, Cochrane Library, Weipu Journal, China Knowledge Network, and Wanfang database was conducted. Two reviewers independently extracted data and methodological quality assessment. Data analysis was performed using Rev Man 5.3 software for statistical analysis. Results. A total of 10 randomized controlled trials, including 661 patients, were included. The results showed that Yiqi Yangyin Huoxue method could significantly improve the vision [risk ratio (RR)=1.32, 95% confidence interval (CI) (1.18, 1.47), P<0.00001] and change the eye fundus [RR=1.23, 95% CI (1.10, 1.37), P=0.0002], fundus fluorescence angiography (FFA) [RR=1.33, 95% CI (1.11, 1.60), P=0.002], traditional Chinese medicine syndromes [RR=1.31, 95% CI (1.15, 1.49), P<0.0001], and hemorheological parameters [mean difference (MD) =-0.37, 95% CI (-0.41, -0.32), P<0.00001]. Conclusion. Yiqi Yangyin Huoxue method showed beneficial effects for DR on improving vision, eye fundus, FFA, TCM syndromes, and hemorheological parameters.

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