scholarly journals Müller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa

2021 ◽  
Author(s):  
Yohei Tomita ◽  
Chenxi Qiu ◽  
Edward Bull ◽  
William Allen ◽  
Yumi Kotoda ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Structural Changes ◽  
Cellular Responses ◽  
Retinal Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Wild Type Littermate ◽  
Rods And Cones ◽  
Expression Of Genes ◽  
Photoreceptor Development

AbstractPhotoreceptor degeneration caused by genetic defects leads to retinitis pigmentosa, a rare disease typically diagnosed in adolescents and young adults. In most cases, rod loss occurs first, followed by cone loss as well as altered function in cells connected to photoreceptors directly or indirectly. There remains a gap in our understanding of retinal cellular responses to photoreceptor abnormalities. Here, we utilized single-cell transcriptomics to investigate cellular responses in each major retinal cell type in retinitis pigmentosa model (P23H) mice vs. wild-type littermate mice. We found a significant decrease in the expression of genes associated with phototransduction, the inner/outer segment, photoreceptor cell cilium, and photoreceptor development in both rod and cone clusters, in line with the structural changes seen with immunohistochemistry. Accompanying this loss was a significant decrease in the expression of genes involved in metabolic pathways and energy production in both rods and cones. We found that in the Müller glia/astrocyte cluster, there was a significant increase in gene expression in pathways involving photoreceptor maintenance, while concomitant decreases were observed in rods and cones. Additionally, the expression of genes involved in mitochondrial localization and transport was increased in the Müller glia/astrocyte cluster. The Müller glial compensatory increase in the expression of genes downregulated in photoreceptors suggests that Müller glia adapt their transcriptome to support photoreceptors and could be thought of as general therapeutic targets to protect against retinal degeneration.

scholarly journals Retinal morphology in Astyanax mexicanus during degeneration

2019 ◽  
Author(s):  
Amany Emam ◽  
Marina Yoffe ◽  
Henry Cardona ◽  
Daphne Soares
Keyword(s):  
Retinitis Pigmentosa ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Diseases ◽  
Muller Glia ◽  
Müller Glia ◽  
Astyanax Mexicanus ◽  
Outer Segments

AbstractThe teleost Astyanax mexicanus is extant in two readily available forms. One that lives in Mexican rivers and various convergent forms that live in nearby caves. These fish are born with eyes but in the cavefish they degenerate during development. It is known that the lens of cavefish undergoes apoptosis and that some cells in the neuroretina also die. It has not been described, however, if glia and various components of the neuroretina form before complete eye degeneration. Here we examined the development of the retina of the closest living ancestor that lives in the rivers and members of two lineages of cavefish. We report that although the neuroretina is smaller and more compact, it has all cell types and layers including amacrine cells and Muller glia. While various makers for photoreceptors are present in the cavefish inner segments, the outer segments of the photoreceptors in cavefish are missing from the earliest stages examined. This shows that the machinery for visual transducing discs might still be present but not organized in one part of the cell. It is interesting to note that the deficiencies in Astyanax cavefish resemble retinal diseases, such as retinitis pigmentosa.

scholarly journals Temporal regulation of Pten is essential for retina regeneration in zebrafish

2021 ◽  
Author(s):  
Shivangi Gupta ◽  
Poonam Sharma ◽  
Mansi Choudhary ◽  
Sharanya Premraj ◽  
Simran Kaur ◽  
...  
Keyword(s):  
Cell Types ◽  
Acute Injury ◽  
Retinal Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Phosphatase And Tensin Homolog ◽  
Temporal Regulation ◽  
Retina Regeneration ◽  
Tensin Homolog ◽  
Ability To Regenerate

Unlike mammals, zebrafish possess a remarkable ability to regenerate damaged retina after an acute injury. Retina regeneration in zebrafish involves the induction of Müller glia-derived progenitor cells (MGPCs) exhibiting stem cell-like characteristics, which are capable of restoring all retinal cell-types. Here, we explored the importance of Phosphatase and tensin homolog (Pten), a dual-specificity phosphatase and tumor suppressor during retina regeneration. The Pten undergo rapid downregulation in the Müller glia and is absent in MGPCs, which is essential to trigger Akt-mediated cell proliferation to cause retina regeneration. We found that the forced downregulation of Pten accelerates MGPCs formation, while its overexpression restricts the regenerative response. We observed that Pten regulates the proliferation of MGPCs not only through Akt pathway but also by Mmp9/Notch signaling. Mmp9-activity is essential to induce the proliferation of MGPCs in the absence of Pten. Lastly, we show that Pten expression is fine-tuned through Mycb/histone deacetylase1 and Tgf-β signaling. The present study emphasizes on the stringent regulation of Pten and its crucial involvement during the zebrafish retina regeneration.

scholarly journals Evidence of Müller glia conversion into retina ganglion cells using Neurogenin2

2018 ◽  
Author(s):  
Roberta Pereira de Melo Guimarães ◽  
Bruna Soares Landeira ◽  
Diego Marques Coelho ◽  
Daiane Cristina Ferreira Golbert ◽  
Mariana S. Silveira ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
The Elderly ◽  
Retinal Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Neuronal Genes ◽  
Consistent Increase ◽  
Induced Neurons

AbstractMacular Degeneration, Glaucoma, and Retinitis Pigmentosa are all leading causes of irreversible visual impairment in the elderly, affecting hundreds of millions of patients. Müller glia cells (MGC), the main type of glia found in the vertebrate retina, can resume proliferation in the adult injured retina and contribute to tissue repair. Also, MGC can be genetically reprogrammed through the expression of the transcription factor (TF) Achaete-scute homolog 1 (ASCL1) into induced neurons (iNs), displaying key hallmarks of photoreceptors, bipolar and amacrine cells, which may contribute to regenerate the damaged retina. Here, we show that the TF neurogenin 2 (NEUROG2) is also sufficient to lineage-reprogram MGC into iNs. The efficiency of MGC lineage conversion by NEUROG2 is similar to that observed after expression of ASCL1. However, reprogramming efficiency is affected by previous exposure to EGF and FGF2 during the expansion of MGC population. Transduction of either Neurog2 or Ascl1 led to the upregulation of key retina neuronal genes in MGC-derived iNs, but only NEUROG2 induced a consistent increase in the expression of putative retinal ganglion cell (RGC) genes. In vivo electroporation of Neurog2 in the neonatal retina also induced a shift in the generation of retinal cell subtypes, favoring the differentiation RGCs at the expense of MGCs. Altogether, our data indicate that Neurog2 induces lineage conversion of MGCs into RGC-like iNs.

Müller Glia-Mediated Retinal Regeneration

2021 ◽  
Author(s):  
Hui Gao ◽  
Luodan A ◽  
Xiaona Huang ◽  
Xi Chen ◽  
Haiwei Xu
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Retinal Regeneration

Müller glia–myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish

Glia ◽  
2021 ◽  
Author(s):  
Annelies Van Dyck ◽  
Ilse Bollaerts ◽  
An Beckers ◽  
Sophie Vanhunsel ◽  
Nynke Glorian ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Myeloid Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Adult Zebrafish ◽  
Optic Nerve Regeneration ◽  
Cell Crosstalk

d-Serine regulates CREB phosphorylation induced by NMDA receptor activation in Müller glia from the retina

2007 ◽  
Vol 427 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Mónica Lamas ◽  
Irene Lee-Rivera ◽  
Mónica Ramírez ◽  
Ana María López-Colomé
Keyword(s):  
Nmda Receptor ◽  
Receptor Activation ◽  
Muller Glia ◽  
Müller Glia ◽  
Creb Phosphorylation ◽  
Nmda Receptor Activation

scholarly journals The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

2016 ◽  
Vol 27 (24) ◽  
pp. 3791-3799 ◽  
Author(s):  
Hafida Sellou ◽  
Théo Lebeaupin ◽  
Catherine Chapuis ◽  
Rebecca Smith ◽  
Anna Hegele ◽  
...  
Keyword(s):  
Dna Damage ◽  
Structural Changes ◽  
Cellular Responses ◽  
Dna Lesions ◽  
Fast Kinetics ◽  
Important Player ◽  
Chromatin Relaxation ◽  
Kinetics Of ◽  
Laser Microirradiation

Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl)ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)- and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD+- and ATP-dependent chromatin relaxation upon DNA damage in vivo.

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