Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy

Wu, Yiwei; Zou, Haidong

doi:10.3390/antiox11112250

Cited by 11 publications

(9 citation statements)

References 210 publications

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“…Persistent hyperglycemia damages mitochondrial function in various types of retinal cells, contributing to DR. 27 Mitochondrial DNA (mtDNA) is epigenetically modified under hyperglycemic conditions, resulting in mitochondrial damage. 28 Apart from alterations in mtDNA, levels of various nuclear genome-encoded lncRNAs, such as NEAT1, MALAT1, and HOTTIP, are elevated in DR. 11 , 29 , 30 Although mitochondria have their separate set of genomes, namely mtDNA, nuclear-encoded lncRNAs can translocate into mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

Zhu

Cheng

Kuang

2023

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the mechanism that long noncoding RNA NEAT1 (lncNEAT1)/miR-320a competitive endogenous RNA (ceRNA) network regulates hypoxia-inducible factor–1α (HIF-1α) in ARPE-19 cells and its potential role in diabetic retinopathy (DR). Methods ARPE-19 cells were cultured in a normal or high-glucose (HG) medium, and cell migration, invasion, and permeability were detected by scratch, transwell, and FITC-dextran staining assays. LncNEAT1, HIF-1α, ZO-1, occludin, N-cadherin, and vimentin levels were tested. The binding of lncNEAT1 to miR-320a was verified by dual-luciferase reporter assay, and the binding of miR-320a to HIF-1α by RIP assay. ARPE-19 cells were treated with lncNEAT1 or HIF-1α shRNA or miR-320a agomir to determine the activation of ANGPTL4/p-STAT3 pathway. The effect of lncNEAT1 in DR and its regulations on miR-320a and HIF-1α were determined in a rat model of DR. Results HG treatment promoted the migration, invasion, and permeability of ARPE-19 cells. After lncNEAT1 silencing, HIF-1α, N-cadherin, and vimentin levels were downregulated, ZO-1 and occludin levels were upregulated, and the migration, permeability, and invasion of HG-treated ARPE-19 cells were inhibited. However, HIF-1α overexpression increased N-cadherin and vimentin expression, reduced ZO-1 and occludin expression, and promoted the migration, permeability, and invasion of ARPE-19 cells. The binding of miR-320a with both lncNEAT1 and HIF-1α was predicted and confirmed. In a diabetic rat model, silencing lncNEAT1 inhibited HIF-1α/ANGPTL4/p-STAT3 pathway activation and alleviated retinopathy. Conclusions The lncNETA1/miR-320a/HIF-1α ceRNA network activates the ANGPTL4/p-STAT3 pathway and promotes HG-induced ARPE-19 cell invasion and migration.

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Section: Discussionmentioning

confidence: 99%

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

Zhu

Cheng

Kuang

2023

Invest. Ophthalmol. Vis. Sci.

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“…Microvascular abnormalities within the retina include retinal vascular leakage and decellularized capillaries ( 149 ). In the pathogenesis of DR, accelerated capillary apoptosis by mitochondrial dysfunction is prior to the development of the histopathological features of DR ( 150 , 151 ).…”

Section: The Function Of Mitochondrial Dynamics In T2d and Its Compli...mentioning

confidence: 99%

“…However, even if hyperglycemia is reversed to normal blood sugar levels, mitochondrial dynamics will still be impaired ( 160 ). Reduced fusion and increased fission of mitochondria eventually stimulate the discharge of Cyt c, inducing apoptosis in retinal cells like RECs and Müller cells ( 151 ). Thus, maintaining mitochondrial quality control and interfering with metabolic memory phenomena by directly regulating mitochondrial dynamics prevents further progression of DR ( 161 ).…”

Section: The Function Of Mitochondrial Dynamics In T2d and Its Compli...mentioning

confidence: 99%

New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics

Wang,

Zhao,

Lin

et al. 2023

Front. Endocrinol.

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As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.

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“…Підвищення вмісту GLUT3 у осіб із гіперглікемією, який навпаки мав би зменшуватися і бути перешкодою та/або регулятором надходження зайвої глюкози до нейронів, зокрема сітківки, визначає схильність нервової тканини до ушкодження. І це в черговий раз пояснює запропоновану майже 25 років тому теорію етіології ДР, яка постулювала, що індукована гіперглікемією продукція вільних радикалів кисню лежить в основі ушкодження сітківки [14].…”

Section: результати та їх обговоренняunclassified

Glucose Transporters of Glut Family in the Pathogenesis of Proliferative Diabetic Retinopathy in Patients With Type 2 Diabetes

Ganyuk,

Petrenko,

Natrus

2023

Fiziol Zh

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The supply of glucose to neurons of the brain and retina is carried out by a specific, facilitated transport with the participation of sodium-independent glucose transporters of the GLUT family. Studying the mechanisms of glucose transport with pharmacological or genetic inhibition of transporters is considered as a promising way to reduce glucose-toxic damage to the retina to prevent diabetic retinopathy. We studied the content of GLUT1, GLUT3, GLUT4 and Hypoxia inducible factor 1 alpha (HIF-1α) in the plasma of patients with different stages of proliferative diabetic retinopathy (PDR), duration of type 2 diabetes (T2D) was up to 20 and over 20 years, and control group. Research on the level of transporters in the blood plasma was carried out by the method of immuno-enzymatic analysis using Elabscience kits (USA). No significant difference in the GLUT1 and GLUT4 blood plasma content was found between patients with PDR and control individuals, and the GLUT3 content was 2-fold higher. Also, the content of HIF-1α was 25% higher. No significant fluctuations in the content of transporters GLUT1, GLUT3, GLUT4, HIF-1α were found depending on the duration of T2DM, the degree of deepening of PDR and the level of hyperglycemia. Correlation analysis revealed a significant two-way correlation of the GLUT3 index with blood glucose level (r = 0.581), HbA1C (r = 0.553), GLUT1 (r = 0.440) and GLUT4 (r = 0.372). The conservatism of GLUT1 transporter content in the studied groups gives a reason to consider protein expression as genetically determined for the basic maintenance of homeostasis. The GLUT3 content increase in patients with PDR, which does not depend on the retinal damage degree, duration of T2D and glucose concentration, defines this mechanism of transport as the main pathogenetic link of glucose toxicity in neurons against the background of chronic hyperglycemia. Insulin-dependent transporter GLUT4 is probably not involved in the occurrence of PDR under of T2D.

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Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy

Cited by 11 publications

References 210 publications

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

Regulation of Long Noncoding RNA NEAT1/miR-320a/HIF-1α Competitive Endogenous RNA Regulatory Network in Diabetic Retinopathy

New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics

Glucose Transporters of Glut Family in the Pathogenesis of Proliferative Diabetic Retinopathy in Patients With Type 2 Diabetes

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