Influence of microglia on retinal progenitor cell turnover and cell replacement

Dick, Andrew D.

doi:10.1038/eye.2008.380

Cited by 19 publications

(12 citation statements)

References 45 publications

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“…However, cellular migration was primarily not observed until 6 to 8 weeks after transplantation. 14,15,46 In this study, independent of the lesion type, an unchanged small number (Ͻ3%) of globular macrophages, compared with the number in the control retinas, was exclusively found in the fiber layer and not in the retinal parenchyma. This result is in accordance with that in a previous study that demonstrated that microbead-labeled, circulating, bone marrow-derived macrophages entered the NFL, but no other retinal layer.…”

Section: Retinal Microglia After On Lesionmentioning

confidence: 76%

Proliferative Response of Microglia and Macrophages in the Adult Mouse Eye after Optic Nerve Lesion

Wohl

Schmeer

Witte

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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Section: Retinal Microglia After On Lesionmentioning

confidence: 76%

Proliferative Response of Microglia and Macrophages in the Adult Mouse Eye after Optic Nerve Lesion

Wohl

Schmeer

Witte

et al. 2010

Invest. Ophthalmol. Vis. Sci.

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“…The fms gene, which codes for csf-1r, is expressed in all macrophage lineage cells and is crucial for their colonization of embryonic tissues [4, 5]. Recently, a concept has emerged that in both the normal and injured brain, microglia function to regulate neurogenesis [6, 7]. Array studies performed in our lab identified progranulin-a ( pgrn-a , GenBank: NM_001001949) as a gene that was strongly upregulated during the proliferative phase of photoreceptor regeneration in zebrafish [8].…”

Section: Introductionmentioning

confidence: 99%

The role of microglia in the neurogenesis of zebrafish retina

Huang

Cui

et al. 2012

Biochemical and Biophysical Research Communications

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Microglia are cells from non-neuronal lineages that reside in the central nervous system. In zebrafish, early macrophages migrate from the yolk sac to the brain and retina at 26–30 hours post fertilization (hpf) and transform into microglia at 55–60 hpf. The migration of macrophages into the central nervous system requires signaling by macrophage colony stimulating factor-1 receptor (csf-1r), which is encoded by the gene fms. In this study, we show that the targeted knockdown of csf-1r with morpholino oligonucleotides delays migration of macrophages from the yolk sac to the retina, and this delay in macrophage migration results in microphthalmia, delay in cell cycle withdrawal among retinal progenitors and the absence of neuronal differentiation. When embryos were allowed to survive beyond the time when morpholino-dependent translation inhibition is lost, microglia re-occupy the retina and neuronal differentiation partially recovers. Our data demonstrate that microglia are required for normal retinal growth and neurogenesis. This study provides new insight into the neurogenic role of microglia during retinal development in zebrafish.

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“…In the chicken retina, microglia and/or macrophages are required for exogenous factor stimulation of MG/progenitor cell proliferation following excitotoxic injury (33). Conversely, activated microgliaassociated signaling molecules, such as IL-6, CXCL10, and TNF-α, have been shown to inhibit human retinal stem/progenitor proliferation and differentiation in culture (34). However, because chicken and mammalian retinas have a limited capacity to regenerate (35), it can be unclear to what extent retinal stem/ progenitor cell proliferation in these systems is indicative of a proor anti-reparative response (i.e., proliferative gliosis).…”

Section: Significancementioning

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.

152

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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Influence of microglia on retinal progenitor cell turnover and cell replacement

Cited by 19 publications

References 45 publications

Proliferative Response of Microglia and Macrophages in the Adult Mouse Eye after Optic Nerve Lesion

Proliferative Response of Microglia and Macrophages in the Adult Mouse Eye after Optic Nerve Lesion

The role of microglia in the neurogenesis of zebrafish retina

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

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