Reactive gliosis in the adult zebrafish retina

Thomas, Jessica; Ranski, Alexandra H.; Morgan, Gregory W.; Thummel, Ryan

doi:10.1016/j.exer.2015.09.017

Cited by 76 publications

(84 citation statements)

References 57 publications

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“…If the upregulation of vimentin is associated with glial cell proliferation, it could be suggested that high levels of vimentin may reflect the active Müller glia/progenitor proliferation that contribute to the formation of the new retinal structure in the regenerating zebrafish retina. Recent studies have highlighted the role that Müller glia plays in the injured zebrafish retina, where persistent gliosis diminishes the ability of these cells to induce regeneration39. In addition, initial upregulation of vimentin in the adult zebrafish brain after injury has been observed, suggesting that early responses to CNS lesions present characteristics of gliosis40.…”

Section: Discussionmentioning

confidence: 99%

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration

Eastlake

Heywood

Tracey‐White

et al. 2017

Sci Rep

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Zebrafish spontaneously regenerate the retina after injury. Although the gene expression profile has been extensively studied in this species during regeneration, this does not reflect protein function. To further understand the regenerative process in the zebrafish, we compared the proteomic profile of the retina during injury and upon regeneration. Using two-dimensional difference gel electrophoresis (2D-DIGE) and label-free quantitative proteomics (quadrupole time of flight LC-MS/MS), we analysed the retina of adult longfin wildtype zebrafish at 0, 3 and 18 days after Ouabain injection. Gene ontology analysis indicates reduced metabolic processing, and increase in fibrin clot formation, with significant upregulation of fibrinogen gamma polypeptide, apolipoproteins A-Ib and A-II, galectin-1, and vitellogenin-6 during degeneration when compared to normal retina. In addition, cytoskeleton and membrane transport proteins were considerably altered during regeneration, with the highest fold upregulation observed for tubulin beta 2 A, histone H2B and brain type fatty acid binding protein. Key proteins identified in this study may play an important role in the regeneration of the zebrafish retina and investigations on the potential regulation of these proteins may lead to the design of protocols to promote endogenous regeneration of the mammalian retina following retinal degenerative disease.

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Section: Discussionmentioning

confidence: 99%

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration

Eastlake

Heywood

Tracey‐White

et al. 2017

Sci Rep

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“…chronic inflammation and related immune cell infiltration of the CNS are believed to exacerbate neurodegenerative pathologies (43). Interestingly, zebrafish regenerate neural tissue despite mounting an inflammatory response to injury (58). Indeed, inflammatory signaling may even stimulate neural stem cell proliferation (11,33,38).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

White¹,

Sengupta²,

Saxena³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

159

218

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Müller glia (MG) function as inducible retinal stem cells in zebrafish, completely repairing the eye after damage. The innate immune system has recently been shown to promote tissue regeneration in which classic wound-healing responses predominate. However, regulatory roles for leukocytes during cellular regeneration-i.e., selective cell-loss paradigms akin to degenerative disease-are less well defined. To investigate possible roles innate immune cells play during retinal cell regeneration, we used intravital microscopy to visualize neutrophil, macrophage, and retinal microglia responses to induced rod photoreceptor apoptosis. Neutrophils displayed no reactivity to rod cell loss. Peripheral macrophage cells responded to rod cell loss, as evidenced by morphological transitions and increased migration, but did not enter the retina. Retinal microglia displayed multiple hallmarks of immune cell activation: increased migration, translocation to the photoreceptor cell layer, proliferation, and phagocytosis of dying cells. To test function during rod cell regeneration, we coablated microglia and rod cells or applied immune suppression and quantified the kinetics of (i) rod cell clearance, (ii) MG/progenitor cell proliferation, and (iii) rod cell replacement. Coablation and immune suppressants applied before cell loss caused delays in MG/progenitor proliferation rates and slowed the rate of rod cell replacement. Conversely, immune suppressants applied after cell loss had been initiated led to accelerated photoreceptor regeneration kinetics, possibly by promoting rapid resolution of an acute immune response. Our findings suggest that microglia control MG responsiveness to photoreceptor loss and support the development of immune-targeted therapeutic strategies for reversing cell loss associated with degenerative retinal conditions. retina | microglia | glucocorticoid | regeneration | macrophage N eurodegenerative diseases are caused by the loss of discrete neuronal cell types. The goal of regenerative medicine is to reverse this process. One strategy for doing so involves harnessing the regenerative potential of endogenous neural stem cells. Unfortunately, although adult neural stem cells exist in the mammalian CNS, innate potentials for neuronal repair remain dormant in the absence of exogenous stimulation. Conversely, many other species are endowed with remarkable capacities for neuronal regeneration. For instance, in the zebrafish eye, retinal Müller glia (MG) cells can dedifferentiate to a stem cell-like state and give rise to progenitors that replace lost neurons and restore visual function (1, 2). Intriguingly, human MG cells are able to give rise to new neurons in culture (3) that can restore visual function when transplanted into mammalian disease models (4), suggesting that human MG retain a stem cell-like capacity for mediating retinal repair. Mechanisms controlling the regenerative potential of MG are therefore of great interest. We and others study zebrafish to learn more about how retinal regeneration is cont...

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“…Only rarely do Müller glia divide following retinal injury in mammals, and when they do they often result in fibrosis and glial scarring 4 . Interestingly, Müller glia in zebrafish respond to retinal injury by initiating a gliotic response that is characterized by hypertrophy and increased Gfap expression 7 . However, this gliotic response is transient in fish and accompanied by a reprogramming event that allows injury-responsive Müller glia to adopt properties of a retinal stem cell (Fig.…”

Section: Müller Glia and Their Behavior In The Damaged Retinamentioning

confidence: 99%

“…All of these factors are expressed by Müller glia-derived progenitors and therefore, may act in an autocrine and paracrine fashion to stimulate Müller glia and progenitor proliferation. It is worth mentioning that Müller glia have been shown to act as phagocytic cells by engulfing apoptotic photoreceptor cell bodies and this phagocytosis was necessary for Müller glia proliferation after injury 7,25 . The significance of this phagocytosis is not completely clear although it has been speculated that it may impact progenitor fate 25 .…”

Section: Signaling Mechanisms Underlying Müller Glia Reprogramming Anmentioning

confidence: 99%

Retina regeneration in zebrafish

Wei

Goldman

2016

Current Opinion in Genetics & Development

215

212

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Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Müller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neuron types. The fish and mammalian retina are composed of similar cell types with conserved function. Because of this it is anticipated that studies of retina regeneration in fish may suggest strategies for stimulating Müller glia reprogramming and retina regeneration in mammals. In this review we describe recent advances and future directions in retina regeneration research using zebrafish as a model system.

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Reactive gliosis in the adult zebrafish retina

Cited by 76 publications

References 57 publications

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration

Immunomodulation-accelerated neuronal regeneration following selective rod photoreceptor cell ablation in the zebrafish retina

Retina regeneration in zebrafish

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