scholarly journals Metabolic Imbalance Effect on Retinal Müller Glial Cells Reprogramming Capacity: Involvement of Histone Deacetylase SIRT6

2021 ◽  
Vol 12 ◽  
Author(s):  
L Francisco Sanhueza Salas ◽  
Alfredo García-Venzor ◽  
Natalia Beltramone ◽  
Claudia Capurro ◽  
Debra Toiber ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Histone Deacetylase ◽  
Glial Cells ◽  
High Glucose ◽  
Müller Cells ◽  
Enrichment Analysis ◽  
Regulatory Elements ◽  
Muller Cells ◽  
Müller Glial Cells ◽  
And Oxidative Stress

Retinal Müller glial cells (MGs) are among the first to demonstrate metabolic changes during retinal disease and are a potential source of regenerative cells. In response to a harmful stimulus, they can dedifferentiate acquiring neural stem cells properties, proliferate and migrate to the damaged retinal layer and differentiate into lost neurons. However, it is not yet known how this reprogramming process is regulated in mammals. Since glucose and oxygen are important regulatory elements that may help directing stem cell fate, we aimed to study the effect of glucose variations and oxidative stress in Müller cells reprogramming capacity and analyze the participation the histone deacetylase SIRT6, as an epigenetic modulator of this process. We found that the combination of high glucose and oxidative stress induced a decrease in the levels of the marker glutamine synthetase, and an increase in the migration capacity of the cells suggesting that these experimental conditions could induce some degree of dedifferentiation and favor the migration ability. High glucose induced an increase in the levels of the pluripotent factor SOX9 and a decrease in SIRT6 levels accompanied by the increase in the acetylation levels of H3K9. Inhibiting SIRT6 expression by siRNA rendered an increase in SOX9 levels. We also determined SOX9 levels in retinas from mice with a conditional deletion of SIRT6 in the CNS. To further understand the mechanisms that regulate MGs response under metabolic impaired conditions, we evaluated the gene expression profile and performed Gene Ontology enrichment analysis of Müller cells from a murine model of Diabetes. We found several differentially expressed genes and observed that the transcriptomic change involved the enrichment of genes associated with glucose metabolism, cell migration, development and pluripotency. We found that many functional categories affected in cells of diabetic animals were directly related to SIRT6 function. Transcription factors enrichment analysis allowed us to predict several factors, including SOX9, that may be involved in the modulation of the differential expression program observed in diabetic MGs. Our results underline the heterogeneity of Müller cells response and the challenge that the study of metabolic impairment in vivo represents.

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

PLoS ONE ◽  
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.

scholarly journals Blockade of Adenosine A2A Receptor Protects Photoreceptors after Retinal Detachment by Inhibiting Inflammation and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Sha Gao ◽  
Na Li ◽  
Yanuo Wang ◽  
Yisheng Zhong ◽  
Xi Shen
Keyword(s):  
Oxidative Stress ◽  
Retinal Detachment ◽  
Müller Cells ◽  
Muller Cells ◽  
Damage Models ◽  
A2a Receptor ◽  
Common Etiology ◽  
Retinal Inflammation ◽  
Adenosine A2a ◽  
And Oxidative Stress

Purpose. Adenosine A2A receptor (A2AR) signaling is neuroprotective in some retinal damage models, but its role in neuronal survival during retinal detachment (RD) is unclear. We tested the hypothesis that A2AR antagonist ZM241385 would prevent photoreceptor apoptosis by inhibiting retinal inflammation and oxidative stress after RD. Methods. The A2AR antagonist ZM241385 was delivered daily to C57BL/6J mice for three days at a dose (3 mg/kg, i.p.) starting 2 hours prior to creating RD. A2AR expression, microglia proliferation and reactivity, glial fibrillary acidic protein (GFAP) accumulation, IL-1β expression, and reactive oxygen species (ROS) production were evaluated with immunofluorescence. Photoreceptor TUNEL was analyzed. Results. A2AR expression obviously increased and accumulated in microglia and Müller cells in the retinas after RD. The A2AR antagonist ZM241385 effectively inhibited retinal microglia proliferation and reactivity, decreased GFAP upregulation and proinflammatory cytokine IL-1β expression of Müller cells, and suppressed ROS overproduction, resulting in attenuation of photoreceptor apoptosis after RD. Conclusions. The A2AR antagonist ZM241385 is an effective suppressor of microglia proliferation and reactivity, gliosis, neuroinflammation, oxidative stress, and photoreceptor apoptosis in a mouse model of RD. This suggests that A2AR blockade may be an important therapeutic strategy to protect photoreceptors in RD and other CNS diseases that share a common etiology.

scholarly journals Effects of hyperglycemia and oxidative stress on the glutamate transporters GLAST and system xc − in mouse retinal Müller glial cells

2009 ◽  
Vol 335 (3) ◽  
pp. 477-488 ◽  
Author(s):  
Barbara Mysona ◽  
Ying Dun ◽  
Jennifer Duplantier ◽  
Vadivel Ganapathy ◽  
Sylvia B. Smith
Keyword(s):  
Oxidative Stress ◽  
Glial Cells ◽  
Glutamate Transporters ◽  
Müller Glial Cells ◽  
And Oxidative Stress

scholarly journals Physiological properties of retinal Müller glial cells from the cynomolgus monkey, Macaca fascicularis—a comparison to human Müller cells

2005 ◽  
Vol 45 (14) ◽  
pp. 1781-1791 ◽  
Author(s):  
Thomas Pannicke ◽  
Bernd Biedermann ◽  
Ortrud Uckermann ◽  
Michael Weick ◽  
Andreas Bringmann ◽  
...  
Keyword(s):  
Glial Cells ◽  
Cynomolgus Monkey ◽  
Macaca Fascicularis ◽  
Müller Cells ◽  
Muller Cells ◽  
Müller Glial Cells ◽  
Physiological Properties

Hydrogen peroxide modulates energy metabolism and oxidative stress in cultures of permanent human Müller cells MIO-M1

2016 ◽  
Vol 10 (9) ◽  
pp. 1180-1188 ◽  
Author(s):  
Sven Peters ◽  
Max Griebsch ◽  
Matthias Klemm ◽  
Jens Haueisen ◽  
Martin Hammer
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Energy Metabolism ◽  
Müller Cells ◽  
Muller Cells ◽  
And Oxidative Stress

scholarly journals Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes

2017 ◽  
Vol 118 (6) ◽  
pp. 3132-3143 ◽  
Author(s):  
Matthew A. Kreitzer ◽  
David Swygart ◽  
Meredith Osborn ◽  
Blair Skinner ◽  
Chad Heer ◽  
...  
Keyword(s):  
Glial Cells ◽  
Müller Cells ◽  
Bicarbonate Transport ◽  
Extracellular Potassium ◽  
Tiger Salamander ◽  
Muller Cells ◽  
Extracellular Acidification ◽  
Müller Glial Cells ◽  
Bicarbonate Transporter ◽  
Induced Changes

Self-referencing H+-selective electrodes were used to measure extracellular H+ fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H+-selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H+ flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H+ flux. Barium at 6 mM also increased H+ flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 μM DIDS, 300 μM SITS, and 30 μM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 μM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H+ fluxes, and removal of the end foot region further decreased the H+ flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H+-selective electrodes can be used to monitor H+ fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell. NEW & NOTEWORTHY The present study uses self-referencing H+-selective electrodes for the first time to measure H+ fluxes from Müller (glial) cells isolated from tiger salamander retina. These studies demonstrate bicarbonate transport as a potent regulator of extracellular levels of acidity around Müller cells and point toward a need for further studies aimed at addressing how such glial cell pH regulatory mechanisms may shape neuronal signaling.

scholarly journals Localization of αA-Crystallin in Rat Retinal Müller Glial Cells and Photoreceptors

2018 ◽  
Vol 24 (5) ◽  
pp. 545-552 ◽  
Author(s):  
Astrid Zayas-Santiago ◽  
David S. Ríos ◽  
Lidia V. Zueva ◽  
Mikhail Y. Inyushin
Keyword(s):  
Glial Cells ◽  
Light Transmission ◽  
Müller Cells ◽  
Cell Types ◽  
Confocal Imaging ◽  
Muller Cells ◽  
Müller Glial Cells ◽  
Fluorescence Confocal Imaging ◽  
Light Guides ◽  
Epithelium Cells

AbstractTransparent cells in the vertebrate optical tract, such as lens fiber cells and corneal epithelium cells, have specialized proteins that somehow permit only a low level of light scattering in their cytoplasm. It has been shown that both cell types contain (1) beaded intermediate filaments as well as (2) α-crystallin globulins. It is known that genetic and chemical alterations to these specialized proteins induce cytoplasmic opaqueness and visual complications. Crystallins were described previously in the retinal Müller cells of frogs. In the present work, using immunocytochemistry, fluorescence confocal imaging, and immuno-electron microscopy, we found that αA-crystallins are present in the cytoplasm of retinal Müller cells and in the photoreceptors of rats. Given that Müller glial cells were recently described as “living light guides” as were photoreceptors previously, we suggest that αA-crystallins, as in other highly transparent cells, allow Müller cells and photoreceptors to minimize intraretinal scattering during retinal light transmission.

Sign in / Sign up

Export Citation Format

Share Document