scholarly journals Retinal Pigment Epithelium and Müller Progenitor Cell Interaction Increase Müller Progenitor Cell Expression of PDGFR and Ability to Induce Proliferative Vitreoretinopathy in a Rabbit Model

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Gisela Velez ◽  
Alexa R. Weingarden ◽  
Budd A. Tucker ◽  
Hetian Lei ◽  
Andrius Kazlauskas ◽  
...  
Keyword(s):  
Cell Line ◽  
Proliferative Vitreoretinopathy ◽  
Progenitor Cell ◽  
Retinal Pigment ◽  
Rabbit Model ◽  
Müller Cells ◽  
Cell Interaction ◽  
Müller Cell ◽  
Muller Cells ◽  
Muller Cell

Purpose. Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE) and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα) is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRαexpression alter Müller cell pathogenicity.Methods. Human MIO-M1 Müller progenitor (MPC) and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα(MIO-M1α) was generated, and tested in a rabbit model for its ability to induce PVR.Results. The expression of PDGFRαand PDGFRβwas upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRαin the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model.Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRαand increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.

scholarly journals RNA sequencing data of cultured primary rat Müller cells, the spontaneously immortalized rat Müller cell line, SIRMu-1, and the SV40-transformed rat Müller cell line, rMC-1

Data in Brief ◽  
2019 ◽  
Vol 23 ◽  
pp. 103721
Author(s):  
Thaksaon Kittipassorn ◽  
Cameron D. Haydinger ◽  
John P.M. Wood ◽  
Teresa Mammone ◽  
Robert J. Casson ◽  
...  
Keyword(s):  
Cell Line ◽  
Rna Sequencing ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Sequencing Data ◽  
Muller Cell

scholarly journals Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1862
Author(s):  
Naouel Gharbi ◽  
Dagne Røise ◽  
Jorunn-Elise Førre ◽  
Amanda J. Edson ◽  
Helena A. Hushagen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Age Dependent ◽  
Muller Cell

The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress.

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

2004 ◽  
Vol 1 (3) ◽  
pp. 291-296 ◽  
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.

scholarly journals TNFα drives the proliferation and inflammatory response, but not regenerative potential of Müller cells in the mouse retina

2019 ◽  
Author(s):  
Lianglaing Niu ◽  
Yuan Fang ◽  
Xiaoqian Yao ◽  
Yi Zhang ◽  
Jihong Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cell ◽  
Müller Cells ◽  
Müller Cell ◽  
Janus Kinase ◽  
Reactive Gliosis ◽  
Muller Cells ◽  
Mapk Pathways ◽  
Retinal Injury ◽  
Muller Cell

Abstract Background Mouse Müller cells, considered dormant retinal progenitors, respond to retinal injury by undergoing reactive gliosis rather than displaying regenerative responses. Tumor necrosis factor alpha (TNFα) is a key cytokine induced after injury, and implicated in mediating inflammatory and regenerative responses. However, the molecular events driving reactive gliosis and regenerative responses in Müller cells, and the role of TNFα in these processes, remain unclear. In this study, we investigated the effects of TNFα on Müller cell responses following injury. Methods To investigate the involvement of TNFα in retinal injury, adult C57BL/6J mice were subjected to treatment with light (5,000 lux) for 14 consecutive days; induction of TNFα was confirmed by quantitative polymerase chain reaction (qPCR). TNFα effects on Müller-cell proliferation were evaluated via 5-ethynyl-2’-deoxyuridine (EdU) incorporation in culture. TNFα-mediated gene profile changes were examined using Affymetrix microarray, and gene ontology analysis was carried out to define the molecular pathways involved. Gene- and protein-expression changes were further verified by qPCR, western blot, and enzyme linked immunosorbent assay (ELISA). Results We showed that TNFα induced Müller cell proliferation and the expression of inflammatory and proliferation-related genes, including NFKBIA, Leukemia inhibitory factor, Interleukin-6, Janus kinase (Jak) 1, Jak2, Signal transducer and activator of transcription (Stat) 1, Stat2, Mitogen-Activated Protein Kinase (MAPK) 7, and MAP4K4. Blockade of Jak/Stat and MAPK pathways attenuated TNFα-induced Müller cell proliferation. Moreover, we detected TNFα drove A1 phenotype-reactive gliosis, while Wnt attenuated TNFα-mediated induction of A1 phenotype and promoted an A2-like phenotype. Conclusion In Müller cells, TNFα triggered primarily inflammatory and reactive gliosis by activating Jak/Stat and MAPK-pathways without inducing progenitor cell/regeneration-related genes. Wnt signaling suppressed inflammation, and induced proliferation and expression of progenitor-cell genes in Müller cells. These results suggest that reactive gliosis and regenerative responses in Müller cells are regulated by independent mechanisms. Our study provides new insights into regulation of inflammatory and regenerative responses of Müller cells in the injured retina

scholarly journals Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: differences in modulation by calcium

2018 ◽  
Vol 120 (3) ◽  
pp. 973-984 ◽  
Author(s):  
Vanina Netti ◽  
Alejandro Pizzoni ◽  
Martha Pérez-Domínguez ◽  
Paula Ford ◽  
Herminia Pasantes-Morales ◽  
...  
Keyword(s):  
Cell Volume ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Müller Cells ◽  
Anion Channel ◽  
Müller Cell ◽  
Regulatory Mechanisms ◽  
Muller Cells ◽  
Muller Cell ◽  
Volume Decrease

Neuronal activity in the retina generates osmotic gradients that lead to Müller cell swelling, followed by a regulatory volume decrease (RVD) response, partially due to the isoosmotic efflux of KCl and water. However, our previous studies in a human Müller cell line (MIO-M1) demonstrated that an important fraction of RVD may also involve the efflux of organic solutes. We also showed that RVD depends on the swelling-induced Ca2+ release from intracellular stores. Here we investigate the contribution of taurine (Tau) and glutamate (Glu), the most relevant amino acids in Müller cells, to RVD through the volume-regulated anion channel (VRAC), as well as their Ca2+ dependency in MIO-M1 cells. Swelling-induced [3H]Tau/[3H]Glu release was assessed by radiotracer assays and cell volume by fluorescence videomicroscopy. Results showed that cells exhibited an osmosensitive efflux of [3H]Tau and [3H]Glu (Tau > Glu) blunted by VRAC inhibitors 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)-oxybutyric acid and carbenoxolone reducing RVD. Only [3H]Tau efflux was mainly dependent on Ca2+ release from intracellular stores. RVD was unaffected in a Ca2+-free medium, probably due to Ca2+-independent Tau and Glu release, but was reduced by chelating intracellular Ca2+. The inhibition of phosphatidylinositol-3-kinase reduced [3H]Glu efflux but also the Ca2+-insensitive [3H]Tau fraction and decreased RVD, providing evidence of the relevance of this Ca2+-independent pathway. We propose that VRAC-mediated Tau and Glu release has a relevant role in RVD in Müller cells. The observed disparities in Ca2+ influence on amino acid release suggest the presence of VRAC isoforms that may differ in substrate selectivity and regulatory mechanisms, with important implications for retinal physiology. NEW & NOTEWORTHY The mechanisms for cell volume regulation in retinal Müller cells are still unknown. We show that swelling-induced taurine and glutamate release mediated by the volume-regulated anion channel (VRAC) largely contributes the to the regulatory volume decrease response in a human Müller cell line. Interestingly, the hypotonic-induced efflux of these amino acids exhibits disparities in Ca2+-dependent and -independent regulatory mechanisms, which strongly suggests that Müller cells may express different VRAC heteromers formed by the recently discovered leucine-rich repeat containing 8 (LRRC8) proteins.

scholarly journals Mediation of FoxO1 in Activated Neuroglia Deficient for Nucleoside Diphosphate Kinase B during Vascular Degeneration

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 280-291 ◽  
Author(s):  
Yi Qiu ◽  
Hongpeng Huang ◽  
Anupriya Chatterjee ◽  
Loïc Teuma ◽  
Fabienne Baumann ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Cell Activation ◽  
Neurovascular Unit ◽  
Nucleoside Diphosphate Kinase ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Nucleoside Diphosphate Kinase B ◽  
Muller Cell ◽  
Underlying Mechanisms

The pathogenesis of diabetic retinopathy is closely associated with the breakdown of the neurovascular unit including the glial cells. Deficiency of nucleoside diphosphate kinase B (NDPK-B) results in retinal vasoregression mimicking diabetic retinopathy. Increased retinal expression of Angiopoietin-2 (Ang-2) initiates vasoregression. In this study, Müller cell activation, glial Ang-2 expression, and the underlying mechanisms were investigated in streptozotocin-induced diabetic NDPK-B deficient (KO) retinas and Müller cells isolated from the NDPK-B KO retinas. Müller cells were activated and Ang-2 expression was predominantly increased in Müller cells in normoglycemic NDPK-B KO retinas, similar to diabetic wild type (WT) retinas. Diabetes induction in the NDPK-B KO mice did not further increase its activation. Additionally, cultured NDPK-B KO Müller cells were more activated and showed higher Ang-2 expression than WT cells. Müller cell activation and Ang-2 elevation were observed upon high glucose treatment in WT, but not in NDPK-B KO cells. Moreover, increased levels of the transcription factor forkhead box protein O1 (FoxO1) were detected in non-diabetic NDPK-B KO Müller cells. The siRNA-mediated knockdown of FoxO1 in NDPK-B deficient cells interfered with Ang-2 upregulation. These data suggest that FoxO1 mediates Ang-2 upregulation induced by NDPK-B deficiency in the Müller cells and thus contributes to the onset of retinal vascular degeneration.

Ranibizumab prevents Müller cell edema by decreasing VEGF-A in diabetic retinopathy

2020 ◽  
Author(s):  
Tianqin Wang ◽  
Chaoyang Zhang ◽  
Hai Xie ◽  
Qiuxue Yi ◽  
Dandan Liu ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Potassium Level ◽  
Müller Cells ◽  
Müller Cell ◽  
Intracellular Sodium ◽  
K Channel ◽  
Diabetic Rat ◽  
Muller Cells ◽  
Intracellular Potassium ◽  
Muller Cell

Abstract Background: Diabetic macular edema (DME) is the most common cause of vision loss in patients with diabetic retinopathy. The efficacy of anti-VEGF therapy has been well demonstrated and become the standard of care in the management of DME. The present study is to explore the possible mechanism(s) of ranibizumab in protecting Müller cells from cellular edema in experimental diabetic retinopathy. Methods: Sprague-Dawley rats were rendered diabetes with intraperitoneal injection of streptozotocin. Intravitreal injection of ranibizumab was performed 8 weeks after diabetes onset. Four weeks later, the rats were killed and the retinas were harvested for examination. rMC-1 cells (rat Müller cell line) were treated with glyoxal for 24 hours, with or without ranibizumab. Cell viability was detected with CCK-8 assay. The expressions of inwardly rectifying K + channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), vascular endothelial growth factor A (VEGF-A), glutamine synthetase (GS) and sodium-potassium-ATPase (Na + -K + -ATPase) were examined with Western blot. VEGF-A in the supernatant of cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators. Results: Compared to the normal control, the protein expressions of Kir4.1, AQP4 and Dp71 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro . As compared with the control, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na + -K + -ATPase protein level remained unchanged. However, ranibizumab treatment increased Na + -K + -ATPase protein expression and decreased intracellular sodium, but not potassium level. Conclusion: Ranibizumab protected Müller cells from intracellular edema through up-regulation of Kir4.1, AQP4, and Dp71 by directly binding VEGF-A. It also increased the expression of Na + -K + -ATPase, contributing to reduction of the intracellular osmotic pressure.

Blockade of amiloride-sensitive sodium channels alters multiple components of the mammalian electroretinogram

2005 ◽  
Vol 22 (2) ◽  
pp. 143-151 ◽  
Author(s):  
LAURA M. BROCKWAY ◽  
DALE J. BENOS ◽  
KENT T. KEYSER ◽  
TIMOTHY W. KRAFT
Keyword(s):  
Physiological Role ◽  
Müller Cells ◽  
Müller Cell ◽  
Cell Physiology ◽  
Muller Cells ◽  
Retinal Neurons ◽  
Multiple Components ◽  
Cell Components ◽  
Slow Piii ◽  
Muller Cell

Retinal neurons and Müller cells express amiloride-sensitive Na+ channels (ASSCs). Although all major subunits of these channels are expressed, their physiological role is relatively unknown in this system. In the present study, we used the electroretinogram (ERG) recorded from anesthetized rabbits and isolated rat and rabbit retina preparations to investigate the physiological significance of ASSCs in the retina. Based upon our previous study showing expression of α-ENaC and functional amiloride-sensitive currents in rabbit Müller cells, we expected changes in Müller cell components of the ERG. However, we observed changes in other components of the ERG as well. The presence of amiloride elicited changes in all major components of the ERG; the a-wave, b-wave, and d-wave (off response) were enhanced, while there was a reduction in the amplitude of the Müller cell response (slow PIII). These results suggest that ASSCs play an important role in retinal function including neuronal and Müller cell physiology.

Müller cell endfeet at the inner surface of the retina: light microscopy

1988 ◽  
Vol 1 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Zofia Dreher ◽  
Mignon Wegner ◽  
Jonathan Stone
Keyword(s):  
Ganglion Cells ◽  
Müller Cells ◽  
Müller Cell ◽  
Postnatal Life ◽  
Muller Cells ◽  
Regular Array ◽  
Differential Growth ◽  
Cat Retina ◽  
Inner Surface ◽  
Muller Cell

AbstractUsing fractions of the protein spectrum of the cat retina as immunogens, we have generated antibodies with substantial specificity for the Müller cells of the retina of cat, rabbit, guinea pig, and rat. The antibodies appear to bind to the filamentous components of the Müller cells and allow demonstration of the pattern of Müller cell endfeet at the inner surface of the retina, best seen in wholemount preparations. In sections and at the edge of wholemount preparations the somas and processes of the cells can be observed. Müller cells are more evenly distributed over the retina than ganglion cells, indicating that their proliferation continues during the differential growth of retina which continues into postnatal life. The morphology and distribution of the endfeet varies with the structures present at the inner surface of the retina. Where the axon bundles are thick, the endfeet are relatively small and are confined to narrow rows between bundles. Müller cell endfeet are also separated widely by large blood vessels. In both situations, it seems likely that Müller cells and astrocytes both contribute, perhaps competitively, to form the glia limitans of the inner surface of the retina. Where the somas of neurones are densely packed in the ganglion cell layer, the endfeet are small and numerous, forming rings around the somas. Where axon bundles, vessels, and somas are sparse, the endfeet appear largest and form a regular array.

Sign in / Sign up

Export Citation Format

Share Document