Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model

Yunhe Xu; Balini Balasubramaniam; Dave A Copland; Jian Liu; M John Armitage; Andrew D Dick

doi:10.1007/s00417-015-2961-y

Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model

Yunhe Xu, Balini Balasubramaniam, Dave A Copland, Jian Liu, M John Armitage, Andrew D Dick

Research output: Contribution to journal › Article (Academic Journal) › peer-review

12 Citations (Scopus)

Abstract

PURPOSE: Microglia contribute to immune homeostasis of the retina, and thus act as a potential regulator determining successful repair or retinal stem cell transplantation. We investigated the interaction between human microglia and retinal progenitor cells in cell co-culture to further our exploration on developing a new therapeutic strategy for retinal degeneration.

METHODS: Microglia and retinal progenitor cultures were developed using CD11b(+) and CD133(+), respectively, from adult donor retina. Microglia activation was developed using interferon-gamma and lipopolysaccharide. Retinal progenitor differentiation was analysed in co-culture with or without microglial activation. Retinal progenitor proliferation was analysed in presence of conditioned medium from activated microglia. Phenotype and function of adult human retinal cell cultures were examined using cell morphology, immunohistochemistry and real-time PCR.

RESULTS: By morphology, neuron-like cells generated in co-culture expressed photoreceptor marker recoverin. Neurospheres derived from retinal progenitor cells showed reduced growth in the presence of conditioned medium from activated microglia. Delayed retinal progenitor cell migration and reduced cellular differentiation was observed in co-cultures with activated microglia. In independent experiments, activated microglia showed enhanced mRNA expression of CXCL10, IL-27, IL-6, and TNF-alpha compared to controls.

CONCLUSION: Adult human retina retains retinal progenitors or potential to reprogram cells to then proliferate and differentiate into neuron-like cells in vitro. Human microglia support retinal progenitor differentiation into neuron-like cells, but such capacity is altered following microglial activation. Modulating microglia activity is a potential approach to promote retinal repair and facilitate success of stem-cell transplantation.

Original language	English
Journal	Graefe's Archive for Clinical and Experimental Ophthalmology
DOIs	https://doi.org/10.1007/s00417-015-2961-y
Publication status	Published - 14 Feb 2015

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@article{a8f001aaeb47418b94b6904059972e74,

title = "Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model",

abstract = "PURPOSE: Microglia contribute to immune homeostasis of the retina, and thus act as a potential regulator determining successful repair or retinal stem cell transplantation. We investigated the interaction between human microglia and retinal progenitor cells in cell co-culture to further our exploration on developing a new therapeutic strategy for retinal degeneration.METHODS: Microglia and retinal progenitor cultures were developed using CD11b(+) and CD133(+), respectively, from adult donor retina. Microglia activation was developed using interferon-gamma and lipopolysaccharide. Retinal progenitor differentiation was analysed in co-culture with or without microglial activation. Retinal progenitor proliferation was analysed in presence of conditioned medium from activated microglia. Phenotype and function of adult human retinal cell cultures were examined using cell morphology, immunohistochemistry and real-time PCR.RESULTS: By morphology, neuron-like cells generated in co-culture expressed photoreceptor marker recoverin. Neurospheres derived from retinal progenitor cells showed reduced growth in the presence of conditioned medium from activated microglia. Delayed retinal progenitor cell migration and reduced cellular differentiation was observed in co-cultures with activated microglia. In independent experiments, activated microglia showed enhanced mRNA expression of CXCL10, IL-27, IL-6, and TNF-alpha compared to controls.CONCLUSION: Adult human retina retains retinal progenitors or potential to reprogram cells to then proliferate and differentiate into neuron-like cells in vitro. Human microglia support retinal progenitor differentiation into neuron-like cells, but such capacity is altered following microglial activation. Modulating microglia activity is a potential approach to promote retinal repair and facilitate success of stem-cell transplantation.",

author = "Yunhe Xu and Balini Balasubramaniam and Copland, {Dave A} and Jian Liu and Armitage, {M John} and Dick, {Andrew D}",

year = "2015",

month = feb,

day = "14",

doi = "10.1007/s00417-015-2961-y",

language = "English",

journal = "Graefe's Archive for Clinical and Experimental Ophthalmology",

issn = "1435-702X",

publisher = "Springer Nature",

}

Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model. / Xu, Yunhe; Balasubramaniam, Balini; Copland, Dave A et al.
In: Graefe's Archive for Clinical and Experimental Ophthalmology, 14.02.2015.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model

AU - Xu, Yunhe

AU - Balasubramaniam, Balini

AU - Copland, Dave A

AU - Liu, Jian

AU - Armitage, M John

AU - Dick, Andrew D

PY - 2015/2/14

Y1 - 2015/2/14

N2 - PURPOSE: Microglia contribute to immune homeostasis of the retina, and thus act as a potential regulator determining successful repair or retinal stem cell transplantation. We investigated the interaction between human microglia and retinal progenitor cells in cell co-culture to further our exploration on developing a new therapeutic strategy for retinal degeneration.METHODS: Microglia and retinal progenitor cultures were developed using CD11b(+) and CD133(+), respectively, from adult donor retina. Microglia activation was developed using interferon-gamma and lipopolysaccharide. Retinal progenitor differentiation was analysed in co-culture with or without microglial activation. Retinal progenitor proliferation was analysed in presence of conditioned medium from activated microglia. Phenotype and function of adult human retinal cell cultures were examined using cell morphology, immunohistochemistry and real-time PCR.RESULTS: By morphology, neuron-like cells generated in co-culture expressed photoreceptor marker recoverin. Neurospheres derived from retinal progenitor cells showed reduced growth in the presence of conditioned medium from activated microglia. Delayed retinal progenitor cell migration and reduced cellular differentiation was observed in co-cultures with activated microglia. In independent experiments, activated microglia showed enhanced mRNA expression of CXCL10, IL-27, IL-6, and TNF-alpha compared to controls.CONCLUSION: Adult human retina retains retinal progenitors or potential to reprogram cells to then proliferate and differentiate into neuron-like cells in vitro. Human microglia support retinal progenitor differentiation into neuron-like cells, but such capacity is altered following microglial activation. Modulating microglia activity is a potential approach to promote retinal repair and facilitate success of stem-cell transplantation.

AB - PURPOSE: Microglia contribute to immune homeostasis of the retina, and thus act as a potential regulator determining successful repair or retinal stem cell transplantation. We investigated the interaction between human microglia and retinal progenitor cells in cell co-culture to further our exploration on developing a new therapeutic strategy for retinal degeneration.METHODS: Microglia and retinal progenitor cultures were developed using CD11b(+) and CD133(+), respectively, from adult donor retina. Microglia activation was developed using interferon-gamma and lipopolysaccharide. Retinal progenitor differentiation was analysed in co-culture with or without microglial activation. Retinal progenitor proliferation was analysed in presence of conditioned medium from activated microglia. Phenotype and function of adult human retinal cell cultures were examined using cell morphology, immunohistochemistry and real-time PCR.RESULTS: By morphology, neuron-like cells generated in co-culture expressed photoreceptor marker recoverin. Neurospheres derived from retinal progenitor cells showed reduced growth in the presence of conditioned medium from activated microglia. Delayed retinal progenitor cell migration and reduced cellular differentiation was observed in co-cultures with activated microglia. In independent experiments, activated microglia showed enhanced mRNA expression of CXCL10, IL-27, IL-6, and TNF-alpha compared to controls.CONCLUSION: Adult human retina retains retinal progenitors or potential to reprogram cells to then proliferate and differentiate into neuron-like cells in vitro. Human microglia support retinal progenitor differentiation into neuron-like cells, but such capacity is altered following microglial activation. Modulating microglia activity is a potential approach to promote retinal repair and facilitate success of stem-cell transplantation.

U2 - 10.1007/s00417-015-2961-y

DO - 10.1007/s00417-015-2961-y

M3 - Article (Academic Journal)

C2 - 25680876

SN - 1435-702X

JO - Graefe's Archive for Clinical and Experimental Ophthalmology

JF - Graefe's Archive for Clinical and Experimental Ophthalmology

ER -

Activated adult microglia influence retinal progenitor cell proliferation and differentiation toward recoverin-expressing neuron-like cells in a co-culture model

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