Long non-coding RNA nuclear paraspeckle assembly transcript 1 inhibits the apoptosis of retina Müller cells after diabetic retinopathy through regulating miR-497/brain-derived neurotrophic factor axis

Background: The role of long non-coding RNA in diabetic retinopathy, a serious complication of diabetes mellitus, has attracted increasing attention in recent years. The purpose of this study was to explore whether long non-coding RNA nuclear paraspeckle assembly transcript 1 was involved in the context of diabetic retinopathy and its underlying mechanisms. Results: Our results revealed that nuclear paraspeckle assembly transcript 1 was significantly downregulated in the retina of diabetes mellitus rats. Meanwhile, miR-497 was significantly increased in diabetes mellitus rats’ retina and high glucose–treated Müller cells, but brain-derived neurotrophic factor was increased. We also found that high glucose–induced apoptosis of Müller cells was accompanied by the significant downregulation of nuclear paraspeckle assembly transcript 1 in vitro. Further study demonstrated that high glucose–promoted Müller cells apoptosis through downregulating nuclear paraspeckle assembly transcript 1 and downregulated nuclear paraspeckle assembly transcript 1 mediated this effect via negative regulating miR-497. Moreover, brain-derived neurotrophic factor was negatively regulated by miR-497 and associated with the apoptosis of Müller cells under high glucose. Conclusion: Our results suggested that under diabetic conditions, downregulated nuclear paraspeckle assembly transcript 1 decreased the expression of brain-derived neurotrophic factor through elevating miR-497, thereby promoting Müller cells apoptosis and aggravating diabetic retinopathy.

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Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain-derived neurotrophic factor

Glia ◽

10.1002/glia.10061 ◽

2002 ◽

Vol 38 (2) ◽

pp. 115-125 ◽

Cited By ~ 63

Author(s):

Hao Chen ◽

Arthur J. Weber

Keyword(s):

Optic Nerve ◽

Glutamine Synthetase ◽

Glial Fibrillary Acidic Protein ◽

Neurotrophic Factor ◽

Müller Cells ◽

Brain Derived Neurotrophic Factor ◽

Nerve Damage ◽

Acidic Protein ◽

Muller Cells ◽

Optic Nerve Damage

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Clinical Utility of Serum Brain-Derived Neurotrophic Factor Levels and its Gene polymorphism Val66Met in Diabetic retinopathy patients with Type 2 Diabetes mellitus

Journal of Recent Advances in Medicine ◽

10.21608/jram.2020.37034.1077 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Arwa Darweesh ◽

Maha Elkishki ◽

Mona Abdel Rassoul ◽

Nour Akl ◽

Eman Mohammed

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Gene Polymorphism ◽

Neurotrophic Factor ◽

Clinical Utility ◽

Brain Derived Neurotrophic Factor ◽

Its Gene

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Long non-coding RNA SNHG16 regulates E2F1 expression by sponging miR-20a-5p and aggravating proliferative diabetic retinopathy

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0693 ◽

2021 ◽

Author(s):

Xiaohua Li ◽

Chenyu Guo ◽

Yong Chen ◽

Feifei Yu

Keyword(s):

Diabetic Retinopathy ◽

Microvascular Dysfunction ◽

Luciferase Reporter ◽

Non Coding Rna ◽

Reporter Assays ◽

Polymerase Chain ◽

Long Non Coding Rna ◽

E2f1 Expression

Long non-coding RNAs (lncRNAs) were reported that related to microvascular dysfunction in diabetic retinopathy (DR), but the potential mechanism remains unknown. This study was designed to elucidate the effects of lncRNA SNHG16 in proliferative DR progression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the levels of SNHG16 and miR-20a-5p from peripheral blood samples of different participants. Pearson’s correlation analysis on the plasma data was applied to detect correlations between SNHG16 and miR-20a-5p. Finally, the interactions of miR-20a-5p and SNHG16 or E2F1 were assessed by luciferase reporter assays. SNHG16 and E2F1 were increased and miR-20a-5p was decreased in proliferative DR both in vivo and in vitro, when compared with control or non-proliferative DR. E2F1 was identified as the target of miR-20a-5p. MiR-20a-5p interacted with SNHG16 and E2F1, and was controlled by SNHG16. The regulation of SNHG16 on E2F1 was mediated by miR-20a-5p. Cells transfected with SNHG16 OE plasmid markedly increased cell apoptosis and vessel-like formation, whereas the miR-20a-5p mimic partially reversed these effects. Transfection with si-E2F1 plasmid rescued SNHG16 overexpression-aggravated proliferative DR. This study indicated that SNHG16 regulated E2F1 expression by sponging miR-20a-5p and aggravating proliferative DR.

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Expression of Glial Cell Line-Derived Neurotrophic Factor and its Receptors in Cultured Retinal Müller Cells Under High Glucose Circumstance

The Anatomical Record ◽

10.1002/ar.22404 ◽

2012 ◽

Vol 295 (3) ◽

pp. 532-539 ◽

Cited By ~ 6

Author(s):

Xinping Zhu ◽

Yan Sun ◽

Zhongping Wang ◽

Weigang Cui ◽

Yuwen Peng ◽

...

Keyword(s):

Cell Line ◽

Glial Cell ◽

High Glucose ◽

Neurotrophic Factor ◽

Müller Cells ◽

Muller Cells

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Mesenchymal marker expression is elevated in Müller cells exposed to high glucose and in animal models of diabetic retinopathy

Oncotarget ◽

10.18632/oncotarget.13945 ◽

2016 ◽

Vol 8 (3) ◽

pp. 4582-4594 ◽

Cited By ~ 8

Author(s):

Ti Zhou ◽

Di Che ◽

Yuqing Lan ◽

Zhenzhen Fang ◽

Jinye Xie ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Animal Models ◽

High Glucose ◽

Müller Cells ◽

Muller Cells ◽

Mesenchymal Marker ◽

Marker Expression

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Downregulation of MicroRNA 29a/b exacerbated diabetic retinopathy by impairing the function of Müller cells via Forkhead box protein O4

Diabetes and Vascular Disease Research ◽

10.1177/1479164118756239 ◽

2018 ◽

Vol 15 (3) ◽

pp. 214-222 ◽

Cited By ~ 9

Author(s):

Jiayu Zhang ◽

Liang Wu ◽

Jiawei Chen ◽

Sisi Lin ◽

Daqiu Cai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Sonic Hedgehog ◽

Müller Cells ◽

Signalling Pathway ◽

Luciferase Reporter ◽

Muller Cells ◽

Forkhead Box ◽

Relationship Of ◽

Endothelial Growth Factor

Background: Diabetic retinopathy is a neurological disease, which can lead to blindness in severe cases. The pathogenesis underlying diabetic retinopathy is unclear. The aim of this study was to explore the role of dysregulated microRNA 29a/b in the onset and progression of diabetic retinopathy. Methods: Diabetes mellitus was induced in rats using 60 mg/kg of streptozotocin. Glucose (5.5 and 25 mM) was used to stimulate rat retinal Müller cells. Real-time polymerase chain reaction and Western blot analyses were used to determine gene expression. A luciferase reporter assay was conducted to validate the relationship of microRNA 29a/b with glioma-associated oncogene homolog 1 and Forkhead box protein O4. Results: The expression of microRNA 29a/b and glutamine synthetase decreased in both diabetes mellitus rats and rat retinal Müller cells stimulated with high glucose, whereas the expression of sonic hedgehog, glioma-associated oncogene homolog 1, glial fibrillary acidic protein, and vascular endothelial growth factor, as well as the content of glutamate, increased. Dysregulated microRNA 29a/b was directly regulated by the sonic hedgehog–glioma-associated oncogene homolog 1 signalling pathway, and microRNA 29a and microRNA 29b targeted Forkhead box protein O4 and regulated its expression. Conclusion: Downregulation of microRNA 29a/b, mediated by the sonic hedgehog–glioma-associated oncogene homolog 1 signalling pathway, exacerbated diabetic retinopathy by upregulating Forkhead box protein O4.

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High Glucose Induces Mitochondrial Dysfunction in Retinal Müller Cells: Implications for Diabetic Retinopathy

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.16-21355 ◽

2017 ◽

Vol 58 (7) ◽

pp. 2915 ◽

Cited By ~ 40

Author(s):

Thomas Tien ◽

Joyce Zhang ◽

Tetsuya Muto ◽

Dongjoon Kim ◽

Vijay P. Sarthy ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Mitochondrial Dysfunction ◽

High Glucose ◽

Müller Cells ◽

Muller Cells

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670nm photobiomodulation modulates bioenergetics and oxidative stress, in rat Müller cells challenged with high glucose

PLoS ONE ◽

10.1371/journal.pone.0260968 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260968

Author(s):

Hannah J. Nonarath ◽

Alexandria E. Hall ◽

Gopika SenthilKumar ◽

Betsy Abroe ◽

Janis T. Eells ◽

...

Keyword(s):

Oxidative Stress ◽

Glial Cells ◽

High Glucose ◽

Near Infrared ◽

Müller Cells ◽

Model System ◽

Light Treatment ◽

Muller Cells ◽

Müller Glial Cells

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-κB (NFκB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Muller glial cells, spanning the entirety of the retina, are involved in DR inflammation. Mitigation of DR pathology currently occurs via invasive, frequently ineffective therapies which can cause adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will diminish oxidative stress preventing downstream inflammatory mechanisms associated with DR initiated by Muller cells. In this study, we used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished reactive oxygen species (ROS) production and preserved mitochondrial integrity in this in vitro model of early DR. Furthermore, treatment for 3 days in culture reduced NFκB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this in vitro high glucose model system suggests light treatment could mitigate early deleterious effects modulating inflammatory signaling and diminishing oxidative stress.

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Unfolded Protein Response Pathways Correlatively Modulate Endoplasmic Reticulum Stress Responses in Rat Retinal Müller Cells

Journal of Ophthalmology ◽

10.1155/2019/9028483 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Shengyu Wu ◽

Xiaolu Zhu ◽

Biechuan Guo ◽

Tian Zheng ◽

Jiangbo Ren ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Transcription Factor ◽

Endoplasmic Reticulum Stress ◽

High Glucose ◽

Müller Cells ◽

Muller Cells ◽

Unfolded Protein ◽

Activating Transcription Factor ◽

Protein Response

Background. Endoplasmic reticulum stress (ERS) in the retinal Müller cells is a key factor contributing to the retinal inflammation and vascular leakage in diabetic retinopathy (DR). This study was to investigate the underlying mechanisms through which the 3 main unfolded protein response (UPR) pathways regulate ERS and to examine the expression levels of vascular endothelial growth factor (VEGF) in Müller cells in vitro. Methods. Rat Müller cell lines were stimulated with high glucose to mimic a diabetic environment in vitro. PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and activating transcription factor 6 (ATF6) were downregulated or upregulated with shRNA or overexpression plasmids. The transfected Müller cells were cultivated in high glucose medium for 48 hours. Expression of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), X-box binding protein 1 (XBP1), ATF6, and VEGF was examined with immunofluorescence and western blot. Results. Our data indicated that ERS was found in both high glucose and osmotic control groups. Overexpression or downregulation of UPR pathways effectively increased or reduced the production of GRP78, ATF4, XBP1, ATF6, and VEGF, respectively. These 3 signaling pathways had similar regulatory effects on VEGF. Conclusion. The 3 UPR-mediated inflammatory pathways were dependent on each other. Inhibition any of these signaling pathways in UPR might be a potential therapeutic target for DR.

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