Wnt Signaling Promotes Müller Cell Proliferation and Survival after Injury

2013 ◽  
Vol 54 (1) ◽  
pp. 444 ◽  
Author(s):  
Bo Liu ◽  
Daniel J. Hunter ◽  
Scott Rooker ◽  
Annie Chan ◽  
Yannis M. Paulus ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Müller Cell ◽  
Muller Cell

scholarly journals Cone Photoreceptor Degeneration and Neuroinflammation in the Zebrafish Bardet-Biedl Syndrome 2 (bbs2) Mutant Does Not Lead to Retinal Regeneration

2020 ◽  
Vol 8 ◽  
Author(s):  
Ping Song ◽  
Joseph Fogerty ◽  
Lauren T. Cianciolo ◽  
Rachel Stupay ◽  
Brian D. Perkins
Keyword(s):  
Cell Proliferation ◽  
Inflammatory Response ◽  
Retinal Degeneration ◽  
Autosomal Recessive Disorder ◽  
Müller Cell ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Retinal Regeneration ◽  
Bardet Biedl Syndrome ◽  
Muller Cell

Bardet-Biedl syndrome (BBS) is a heterogeneous and pleiotropic autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, renal dysfunction, and mental retardation. BBS results from defects in primary and sensory cilia. Mutations in 21 genes have been linked to BBS and proteins encoded by 8 of these genes form a multiprotein complex termed the BBSome. Mutations in BBS2, a component of the BBSome, result in BBS as well as non-syndromic retinal degeneration in humans and rod degeneration in mice, but the role of BBS2 in cone photoreceptor survival is not clear. We used zebrafish bbs2–/– mutants to better understand how loss of bbs2 leads to photoreceptor degeneration. Zebrafish bbs2–/– mutants exhibited impaired visual function as larvae and adult zebrafish underwent progressive cone photoreceptor degeneration. Cone degeneration was accompanied by increased numbers of activated microglia, indicating an inflammatory response. Zebrafish exhibit a robust ability to regenerate lost photoreceptors following retinal damage, yet cone degeneration and inflammation was insufficient to trigger robust Müller cell proliferation. In contrast, high intensity light damage stimulated Müller cell proliferation and photoreceptor regeneration in both wild-type and bbs2–/– mutants, although the bbs2–/– mutants could only restore cones to pre-damaged densities. In summary, these findings suggest that cone degeneration leads to an inflammatory response in the retina and that BBS2 is necessary for cone survival. The zebrafish bbs2 mutant also represents an ideal model to identify mechanisms that will enhance retinal regeneration in degenerating diseases.

scholarly journals TNFα activates MAPK and Jak-Stat pathways to promote mouse Müller cell proliferation

2021 ◽  
Vol 202 ◽  
pp. 108353
Author(s):  
Liangliang Niu ◽  
Yuan Fang ◽  
Xiaoqian Yao ◽  
Yi Zhang ◽  
Jihong Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Müller Cell ◽  
Muller Cell

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

Demonstration of Retinal Glycogen with Silver Methenamine

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.

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

Biomolecules ◽  
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.

scholarly journals The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers

Oncogene ◽  
2021 ◽  
Author(s):  
Hirokazu Kimura ◽  
Ryota Sada ◽  
Naoki Takada ◽  
Akikazu Harada ◽  
Yuichiro Doki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cancer Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Ductal Adenocarcinoma ◽  
Cancer Cell Proliferation ◽  
Positive Feedback Loop ◽  
Dkk1 Expression ◽  
Foxm1 Expression

AbstractDickkopf1 (DKK1) is overexpressed in various cancers and promotes cancer cell proliferation by binding to cytoskeleton-associated protein 4 (CKAP4). However, the mechanisms underlying DKK1 expression are poorly understood. RNA sequence analysis revealed that expression of the transcription factor forkhead box M1 (FOXM1) and its target genes concordantly fluctuated with expression of DKK1 in pancreatic ductal adenocarcinoma (PDAC) cells. DKK1 knockdown decreased FOXM1 expression and vice versa in PDAC and esophageal squamous cell carcinoma (ESCC) cells. Inhibition of either the DKK1-CKAP4-AKT pathway or the ERK pathway suppressed FOXM1 expression, and simultaneous inhibition of both pathways showed synergistic effects. A FOXM1 binding site was identified in the 5ʹ-untranslated region of the DKK1 gene, and its depletion decreased DKK1 expression and cancer cell proliferation. Clinicopathological and database analysis revealed that PDAC and ESCC patients who simultaneously express DKK1 and FOXM1 have a poorer prognosis. Multivariate analysis demonstrated that expression of both DKK1 and FOXM1 is the independent prognostic factor in ESCC patients. Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.

scholarly journals Involvement of NT3 and P75NTR in photoreceptor degeneration following selective Müller cell ablation

2013 ◽  
Vol 10 (1) ◽  
pp. 137 ◽  
Author(s):  
Weiyong Shen ◽  
Ling Zhu ◽  
So-Ra Lee ◽  
Sook H Chung ◽  
Mark C Gillies
Keyword(s):  
Müller Cell ◽  
Photoreceptor Degeneration ◽  
Cell Ablation ◽  
Muller Cell
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