scholarly journals Inflammation Regulates the Multi-Step Process of Retinal Regeneration in Zebrafish

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 783
Author(s):  
Mikiko Nagashima ◽  
Peter F. Hitchcock
Keyword(s):  
Cell Death ◽  
Radial Glia ◽  
Current Knowledge ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Regeneration ◽  
Step Process ◽  
Ability To Regenerate ◽  
Activate Complex ◽  
Almost All

The ability to regenerate tissues varies between species and between tissues within a species. Mammals have a limited ability to regenerate tissues, whereas zebrafish possess the ability to regenerate almost all tissues and organs, including fin, heart, kidney, brain, and retina. In the zebrafish brain, injury and cell death activate complex signaling networks that stimulate radial glia to reprogram into neural stem-like cells that repair the injury. In the retina, a popular model for investigating neuronal regeneration, Müller glia, radial glia unique to the retina, reprogram into stem-like cells and undergo a single asymmetric division to generate multi-potent retinal progenitors. Müller glia-derived progenitors then divide rapidly, numerically matching the magnitude of the cell death, and differentiate into the ablated neurons. Emerging evidence reveals that inflammation plays an essential role in this multi-step process of retinal regeneration. This review summarizes the current knowledge of the inflammatory events during retinal regeneration and highlights the mechanisms whereby inflammatory molecules regulate the quiescence and division of Müller glia, the proliferation of Müller glia-derived progenitors and the survival of regenerated neurons.

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

scholarly journals Characterization of retinal regeneration in adult zebrafish following multiple rounds of phototoxic lesion

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5646 ◽  
Author(s):  
Alexandra H. Ranski ◽  
Ashley C. Kramer ◽  
Gregory W. Morgan ◽  
Jennifer L. Perez ◽  
Ryan Thummel
Keyword(s):  
Cell Cycle ◽  
Cellular Localization ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Inner Plexiform Layer ◽  
Muller Glia ◽  
Müller Glia ◽  
Light Damage ◽  
Retinal Regeneration ◽  
Adult Zebrafish

Müller glia in the zebrafish retina respond to retinal damage by re-entering the cell cycle, which generates large numbers of retinal progenitors that ultimately replace the lost neurons. In this study we compared the regenerative outcomes of adult zebrafish exposed to one round of phototoxic treatment with adult zebrafish exposed to six consecutive rounds of phototoxic treatment. We observed that Müller glia continued to re-enter the cell cycle to produce clusters of retinal progenitors in zebrafish exposed to multiple rounds of phototoxic light. Some abnormalities were noted, however. First, we found that retinas exposed to multiple rounds of damage exhibited a greater loss of photoreceptors at 36 hours of light damage than retinas that were exposed to their first round of light damage. In addition, we found that Müller glia appeared to have an increase in the acute gliotic response in retinas exposed to multiple rounds of light treatment. This was evidenced by cellular hypertrophy, changes in GFAP cellular localization, and transient increases in stat3 and gfap expression. Finally, following the sixth round of phototoxic lesion, we observed a significant increase in mis-localized HuC/D-positive amacrine and ganglion cells in the inner plexiform layer and outer retina, and a decreased number of regenerated blue cone photoreceptors. These data add to recent findings that retinal regeneration in adult zebrafish occurs concomitant with Müller glia reactivity and can result in the generation of aberrant neurons. These data are also the first to demonstrate that Müller glia appear to modify their phenotype in response to multiple rounds of phototoxic lesion, exhibiting an increase in acute gliosis while maintaining a remarkable capacity for long-term regeneration of photoreceptors.

scholarly journals Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

2021 ◽  
Author(s):  
Joshua M. Tworig ◽  
Chandler Coate ◽  
Marla B. Feller
Keyword(s):  
Radial Glia ◽  
Muscarinic Acetylcholine Receptor ◽  
Cytosolic Calcium ◽  
Calcium Transients ◽  
Muller Glia ◽  
Müller Glia ◽  
Pharmacological Agents ◽  
Stage Of Development ◽  
M1 Muscarinic Acetylcholine Receptor ◽  
M1 Muscarinic

AbstractNeural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.

scholarly journals Gene regulatory networks controlling vertebrate retinal regeneration

Science ◽  
2020 ◽  
Vol 370 (6519) ◽  
pp. eabb8598 ◽  
Author(s):  
Thanh Hoang ◽  
Jie Wang ◽  
Patrick Boyd ◽  
Fang Wang ◽  
Clayton Santiago ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Chromatin Accessibility ◽  
Specific Gene ◽  
Muller Glia ◽  
Müller Glia ◽  
Retinal Regeneration ◽  
Adult Mice ◽  
Gene Regulatory

Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicated network suppresses neurogenic competence and restores quiescence. Disruption of nuclear factor I transcription factors, which maintain and restore quiescence, induces Müller glia to proliferate and generate neurons in adult mice after injury. These findings may aid in designing therapies to restore retinal neurons lost to degenerative diseases.

scholarly journals Characterization of Müller glia and neuronal progenitors during adult zebrafish retinal regeneration

2008 ◽  
Vol 87 (5) ◽  
pp. 433-444 ◽  
Author(s):  
Ryan Thummel ◽  
Sean C. Kassen ◽  
Jennifer M. Enright ◽  
Craig M. Nelson ◽  
Jacob E. Montgomery ◽  
...  
Keyword(s):  
Muller Glia ◽  
Müller Glia ◽  
Retinal Regeneration ◽  
Adult Zebrafish ◽  
Neuronal Progenitors

scholarly journals Müller Glia regenerative potential is maintained throughout life despite neurodegeneration and gliosis in the ageing zebrafish retina

2020 ◽  
Author(s):  
Raquel R. Martins ◽  
Mazen Zamzam ◽  
Mariya Moosajee ◽  
Ryan Thummel ◽  
Catarina M. Henriques ◽  
...  
Keyword(s):  
Significant Risk ◽  
Neuronal Loss ◽  
Significant Risk Factor ◽  
Great Promise ◽  
Muller Glia ◽  
Müller Glia ◽  
Light Damage ◽  
Age Related ◽  
Ability To Regenerate ◽  
The Impact

ABSTRACTAgeing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions. Yet, the impact of ageing on MG regenerative capacity has not yet been considered. Here we show that the zebrafish retina undergoes telomerase-independent age-related neurodegeneration. Yet, this progressive neuronal loss in the ageing retina is insufficient to stimulate the MG regenerative response. Instead, age-related neurodegeneration leads to MG gliosis and loss of vision, similarly to humans. Nevertheless, gliotic MG cells retain Yap expression and the ability to regenerate neurons after acute light damage. Therefore, we identify key differences in the MG response to acute versus chronic damage in the zebrafish retina and show that aged gliotic MG can be stimulated to repair damaged neurons in old age.SUMMARYOur data suggest there are key differences between mechanisms driving regeneration in response to acute damage versus age-related chronic damage. It may be that either the number of cells dying in natural ageing is not enough to stimulate MG to proliferate, or the low number of microglia and respective signals released are not sufficient to trigger MG proliferation. Importantly, we show that gliotic MG cells can be stimulated to repair damaged neurons in old zebrafish retina.

scholarly journals Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Joshua M Tworig ◽  
Chandler Coate ◽  
Marla B Feller
Keyword(s):  
Radial Glia ◽  
Muscarinic Acetylcholine Receptor ◽  
Cytosolic Calcium ◽  
Calcium Transients ◽  
Muller Glia ◽  
Müller Glia ◽  
Pharmacological Agents ◽  
Stage Of Development ◽  
M1 Muscarinic Acetylcholine Receptor ◽  
M1 Muscarinic

Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.

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