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 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 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 Muller cells of chicken retina synthesize 11-cis-retinol

1992 ◽  
Vol 285 (3) ◽  
pp. 907-913 ◽  
Author(s):  
S R Das ◽  
N Bhardwaj ◽  
H Kjeldbye ◽  
P Gouras
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Light And Electron Microscopy ◽  
Müller Cells ◽  
Neural Retina ◽  
Retinyl Palmitate ◽  
Immunocytochemical Localization ◽  
Muller Cells ◽  
Trans Isomers ◽  
Chicken Retina

The amounts of endogenous retinyl palmitate, retinol and retinaldehyde were measured in the neural retina and retinal pigment epithelium (RPE) of predominantly cone (chicken), rod (rat) and more mixed (cat, human) retinae. The ratio of 11-cis to all-trans isomers of retinyl palmitate and retinol in the neural retina and the RPE increases progressively with the increase in diurnality of the species from rat to chicken. The membrane fractions of both chicken and bovine RPE enzymically isomerize all-trans retinol to 11-cis-retinol. Chicken neural retina membranes enzymically form 11-cis-retinol and all-trans-retinyl palmitate from all-trans-retinol. Light and electron microscopy revealed no contamination of chicken neural retina by RPE. Muller cells from chicken retina were isolated, cultured and characterized by immunocytochemical localization of cellular retinaldehyde-binding protein. Cultured chicken Muller cells form all-trans-retinyl palmitate, 11-cis-retinol and 11-cis-retinyl palmitate from all-trans-retinol and release most of the 11-cis-retinol into the medium. The results indicate that chicken neural retina and Muller cells in particular synthesize 11-cis-retinoids from all-trans-retinol.

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.

Expression of monocarboxylate transporters in rat ocular tissues

2005 ◽  
Vol 288 (2) ◽  
pp. C416-C428 ◽  
Author(s):  
Glyn Chidlow ◽  
John P. M. Wood ◽  
Mark Graham ◽  
Neville N. Osborne
Keyword(s):  
Ciliary Body ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Basal Membrane ◽  
Monocarboxylate Transporter ◽  
Muller Cells ◽  
Ciliary Processes ◽  
Unique Distribution ◽  
Plexiform Layers

The aim of the present study was to determine the distribution of monocarboxylate transporter (MCT) subtypes 1-4 in the various structures of the rat eye by using a combination of conventional and real-time RT-PCR, immunoblotting, and immunohistochemistry. Retinal samples expressed mRNAs encoding all four MCTs. MCT1 immunoreactivity was observed in photoreceptor inner segments, Müller cells, retinal capillaries, and the two plexiform layers. MCT2 labeling was concentrated in the inner and outer plexiform layers. MCT4 immunolabeling was present only in the inner retina, particularly in putative Müller cells, and the plexiform layers. No MCT3 labeling could be observed. The retinal pigment epithelium (RPE)/choroid expressed high levels of MCT1 and MCT3 mRNAs but lower levels of MCT2 and MCT4 mRNAs. MCT1 was localized to the apical and MCT3 to the basal membrane of the RPE, whereas MCT2 staining was faint. Although MCT1-MCT4 mRNAs were all detectable in iris and ciliary body samples, only MCT1 and MCT2 proteins were expressed. These were present in the iris epithelium and the nonpigmented epithelium of the ciliary processes. MCT4 was localized to the smooth muscle lining of large vessels in the iris-ciliary body and choroid. In the cornea, MCT1 and MCT2 mRNAs and proteins were detectable in the epithelium and endothelium, whereas evidence was found for the presence of MCT4 and, to a lesser extent, MCT1 in the lens epithelium. The unique distribution of MCT subtypes in the eye is indicative of the pivotal role that these transporters play in the maintenance of ocular function.

scholarly journals Creatine transporter localization in developing and adult retina: importance of creatine to retinal function

2005 ◽  
Vol 289 (4) ◽  
pp. C1015-C1023 ◽  
Author(s):  
Monica L. Acosta ◽  
Michael Kalloniatis ◽  
David L. Christie
Keyword(s):  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Nerve Fibers ◽  
Retinal Function ◽  
Mouse Retina ◽  
Muller Cells ◽  
Creatine Transporter ◽  
Subsequent Decrease

Creatine and phosphocreatine are required to maintain ATP needed for normal retinal function and development. The aim of the present study was to determine the distribution of the creatine transporter (CRT) to gain insight to how creatine is transported into the retina. An affinity-purified antibody raised against the CRT was applied to adult vertebrate retinas and to mouse retina during development. Confocal microscopy was used to identify the localization pattern as well as co-localization patterns with a range of retinal neurochemical markers. Strong labeling of the CRT was seen in the photoreceptor inner segments in all species studied and labeling of a variety of inner neuronal cells (amacrine, bipolar, and ganglion cells), the retinal nerve fibers and sites of creatine transport into the retina (retinal pigment epithelium, inner retinal blood vessels, and perivascular astrocytes). The CRT was not expressed in Müller cells of any of the species studied. The lack of labeling of Müller cells suggests that neurons are independent of this glial cell in accumulating creatine. During mouse retinal development, expression of the CRT progressively increased throughout the retina until approximately postnatal day 10, with a subsequent decrease. Comparison of the distribution patterns of the CRT in vascular and avascular vertebrate retinas and studies of the mouse retina during development indicate that creatine and phosphocreatine are important for ATP homeostasis.

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.

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