Muller cell function during spreading depression in frog retina.

Glia-neuron partnership is important for inner retinal homeostasis and any disturbances may result in retinal ganglion cell (RGC) death. Müller cells support RGCs with essential functions such as removing excess glutamate and providing energy sources. The aim was to explore the impact of Müller cells on RGC survival. To investigate the Müller cell/RGC interactions we developed a coculture model, in which primary Müller cells were grown in inserts on top of pure primary RGC cultures. The impact of starvation and mitochondrial inhibition on the Müller cell ability to protect RGCs was studied. Moreover, the ability of Müller cells to remove glutamate from the extracellular space was investigated. RGC survival was evaluated by cell viability assays and glutamate uptake was assessed by kinetic uptake assays. We demonstrated a significantly increased RGC survival in presence of untreated and prestarved Müller cells. Additionally, prestarved Müller cells significantly increased RGC survival after mitochondrial inhibition. Finally, we revealed a significantly increased ability to take up glutamate in starved Müller cells. Overall, our study confirms essential roles of Müller cells in RGC survival. We suggest that targeting Müller cell function could have potential for future treatment strategies to prevent blinding neurodegenerative retinal diseases.

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Cytochemical localization of 5'-nucleotidase in the frog (Rana pipiens) retina. A histochemical and cytochemical study.

Journal of Histochemistry & Cytochemistry ◽

10.1177/33.10.2995482 ◽

1985 ◽

Vol 33 (10) ◽

pp. 1067-1072 ◽

Cited By ~ 4

Author(s):

S T Hussain ◽

E A Baydoun

Keyword(s):

Enzyme Activity ◽

Plasma Membrane ◽

Müller Cell ◽

Inner Plexiform Layer ◽

Cytochemical Localization ◽

Cytochemical Study ◽

Retinal Layers ◽

Frog Retina ◽

Cell Processes ◽

Muller Cell

Localization of 5'-nucleotidase in the frog retina was investigated using histochemical and cytochemical techniques. Light-microscopic observations revealed the presence of this enzyme in the inner retinal layers (the nerve fiber layer, ganglion cell layer, and inner plexiform layer). Ultrastructural investigations revealed that the enzyme activity is associated with the plasma membranes of the Müller cell processes, whereas the Müller cell processes present in the outer retinal layers did not demonstrate any detectable enzyme activity. This observation would appear to confirm our previous findings, that 5'-nucleotidase is an ectoenzyme, but its distribution in frog retina differs from that in rodents and it is only present in the inner layers of the retina. The prominent localization of 5'-nucleotidase on the glial plasma membrane may be viewed in the context of the widely accepted interaction between neurones and glial cells. Since nucleotides do not penetrate the plasma membrane, a mechanism to produce membrane-permeable adenosine, important for neuronal function, is postulated. It is known that 5'-nucleotidase produces adenosine by hydrolyzing adenosine 5'-monophosphate (5'-AMP). Therefore one would expect that the glial membrane-bound enzyme can accomplish the final step in this mechanism by producing the adenosine in the extracellular spaces.

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Blocking IL-17A Alleviates Diabetic Retinopathy in Rodents

Cellular Physiology and Biochemistry ◽

10.1159/000460514 ◽

2017 ◽

Vol 41 (3) ◽

pp. 960-972 ◽

Cited By ~ 21

Author(s):

Ao-Wang Qiu ◽

Qing-Huai Liu ◽

Jun-Ling Wang

Keyword(s):

Diabetic Retinopathy ◽

Intravitreal Injection ◽

Cell Function ◽

Autoimmune Diabetes ◽

Müller Cell ◽

Cell Dysfunction ◽

Junction Protein ◽

Neutralizing Monoclonal Antibody ◽

Muller Cell

Background/Aims: Interleukin (IL)-17A, a proinflammatory cytokine, has been implicated in several autoimmune diseases. However, it is unclear whether IL-17A is involved in diabetic retinopathy (DR), one of the most serious complications of autoimmune diabetes. This study aimed to demonstrate that IL-17A exacerbates DR by affecting retinal Müller cell function. Methods: High glucose (HG)-treated rat Müller cell line (rMC-1) was exposed to IL-17A, anti-IL-17A-neutralizing monoclonal antibody (mAb) or/and anti-IL-17 receptor (R)A-neutralizing mAb for 24 h. For in vivo study, DR was induced by intraperitoneal injections of streptozotocin (STZ). DR model mice were treated with anti-IL-17A mAb or anti-IL-17RA mAb in the vitreous cavity. Mice that were prepared for retinal angiography were sacrificed two weeks after intravitreal injection, while the rest were sacrificed two days after intravitreal injection. Results: IL-17A production and IL-17RA expression were increased in both HG-treated rMC-1 and DR retina. HG induced rMC-1 activation and dysfunction, as determined by the increased GFAP, VEGF and glutamate levels as well as the downregulated GS and EAAT1 expression. IL-17A exacerbated the HG-induced rMC-1 functional disorders, whereas either anti-IL-17A mAb or anti-IL-17RA mAb alleviated the HG-induced rMC-1 disorders. Intravitreal injections with anti-IL-17A mAb or anti-IL-17RA mAb in DR model mice reduced Müller cell dysfunction, vascular leukostasis, vascular leakage, tight junction protein downregulation and ganglion cell apoptosis in the retina. Conclusions: IL-17A aggravates DR-like pathology at least partly by impairing retinal Müller cell function. Blocking IL-17A is a potential therapeutic strategy for DR.

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Contribution of Müller cells toward the regulation of photoreceptor outer segment assembly

Neuron Glia Biology ◽

10.1017/s1740925x05000049 ◽

2004 ◽

Vol 1 (3) ◽

pp. 291-296 ◽

Cited By ~ 5

Author(s):

XIAOFEI WANG ◽

ALESSANDRO IANNACCONE ◽

MONICA M. JABLONSKI

Keyword(s):

Outer Segment ◽

Cell Function ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Müller Cells ◽

Müller Cell ◽

Muller Cells ◽

Outer Segments ◽

Pigment Epithelium Derived Factor ◽

Muller Cell

The assembly of photoreceptor outer segments into stacked discs is a complicated process, the precise regulation of which remains a mystery. It is known that the integrity of the outer segment is heavily dependent upon surrounding cell types including the retinal pigment epithelium and Müller cells; however the role played by Müller cells within this photoreceptor-specific process has not been fully explored. Using an RPE-deprived but otherwise intact Xenopus laevis eye rudiment preparation, we reveal that Müller cell involvement in outer segment assembly is dependent upon the stimulus provided to the retina. Pigment epithelium-derived factor is able to support proper membrane folding after inhibition of Müller cell metabolism by alpha-aminoadipic acid, while isopropyl beta-D-thiogalactoside, a permissive glycan, requires intact Müller cell function. These results demonstrate that both intrinsic and extrinsic redundant mechanisms exist to support the ability of photoreceptors to properly assemble their outer segments. Our study further suggests that the receptor for pigment epithelium-derived factor resides in photoreceptors themselves while that for permissive glycans is likely localized to Müller cells, which in turn communicate with photoreceptors to promote proper membrane assembly.

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670 nm Red Light Preconditioning Supports Müller Cell Function: Evidence from the White Light-induced Damage Model in the Rat Retina†

Photochemistry and Photobiology ◽

10.1111/j.1751-1097.2012.01130.x ◽

2012 ◽

Vol 88 (6) ◽

pp. 1418-1427 ◽

Cited By ~ 30

Author(s):

Rizalyn Albarracin ◽

Krisztina Valter

Keyword(s):

White Light ◽

Cell Function ◽

Red Light ◽

Damage Model ◽

Müller Cell ◽

Rat Retina ◽

Muller Cell

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Purinergic signaling involved in Müller cell function in the mammalian retina

Progress in Retinal and Eye Research ◽

10.1016/j.preteyeres.2011.06.001 ◽

2011 ◽

Vol 30 (5) ◽

pp. 324-342 ◽

Cited By ~ 40

Author(s):

Antje Wurm ◽

Thomas Pannicke ◽

Ianors Iandiev ◽

Mike Francke ◽

Margrit Hollborn ◽

...

Keyword(s):

Cell Function ◽

Purinergic Signaling ◽

Müller Cell ◽

Mammalian Retina ◽

Muller Cell

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Fyn kinase genetic ablation causes structural abnormalities in mature retina and defective Müller cell function

Molecular and Cellular Neuroscience ◽

10.1016/j.mcn.2016.01.008 ◽

2016 ◽

Vol 72 ◽

pp. 91-100 ◽

Cited By ~ 2

Author(s):

Marbella Chavez-Solano ◽

Alfredo Ibarra-Sanchez ◽

Mario Treviño ◽

Claudia Gonzalez-Espinosa ◽

Monica Lamas

Keyword(s):

Cell Function ◽

Müller Cell ◽

Genetic Ablation ◽

Fyn Kinase ◽

Structural Abnormalities ◽

Muller Cell

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Demonstration of Retinal Glycogen with Silver Methenamine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066875 ◽

1971 ◽

Vol 29 ◽

pp. 564-565

Author(s):

A. W. Sedar ◽

G. H. Bresnick

Keyword(s):

Lactic Acid ◽

Chromic Acid ◽

Periodic Acid ◽

Müller Cell ◽

External Limiting Membrane ◽

Electron Microscope Level ◽

Reactive Process ◽

Inner Limiting Membrane ◽

Muller Cell ◽

And Migration

After experimetnal damage to the retina with a variety of procedures Müller cell hypertrophy and migration occurs. According to Kuwabara and others the reactive process in these injuries is evidenced by a marked increase in amount of glycogen in the Müller cells. These cells were considered originally supporting elements with fiber processes extending throughout the retina from inner limiting membrane to external limiting membrane, but are known now to have high lactic acid dehydrogenase activity and the ability to synthesize glycogen. Since the periodic acid-chromic acid-silver methenamine technique was shown to demonstrate glycogen at the electron microscope level, it was selected to react with glycogen in the fine processes of the Müller cell that ramify among the neural elements in various layers of the retina and demarcate these cells cytologically. The Rhesus monkey was chosen as an example of a well vascularized retina and the rabbit as an example of a avascular retina to explore the possibilities of the technique.

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VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes

Biomolecules ◽

10.3390/biom11050712 ◽

2021 ◽

Vol 11 (5) ◽

pp. 712

Author(s):

Yun-Zheng Le ◽

Bei Xu ◽

Ana J. Chucair-Elliott ◽

Huiru Zhang ◽

Meili Zhu

Keyword(s):

Specific Protein ◽

Müller Cell ◽

Dependent Manner ◽

Vascular Abnormalities ◽

Extracellular Signal ◽

Muller Cell ◽

Protein Kinase Akt ◽

Sirna Knockdown ◽

Endothelial Growth Factor ◽

Dose Dependent

To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities.

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