Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model

Shen, Weiyong, Fruttiger, Marcus, Zhu, Ling, Chung, Sook H., Barnett, Nigel L., Kirk, Joshua K., Lee, SoRa, Coorey, Nathan J., Killingsworth, Murray, Sherman, Larry S. and Gillies, Mark C. (2012) Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model. Journal of Neuroscience, 32 45: 15715-15727. doi:10.1523/JNEUROSCI.2841-12.2012

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Author Shen, Weiyong
Fruttiger, Marcus
Zhu, Ling
Chung, Sook H.
Barnett, Nigel L.
Kirk, Joshua K.
Lee, SoRa
Coorey, Nathan J.
Killingsworth, Murray
Sherman, Larry S.
Gillies, Mark C.
Title Conditional müller cell ablation causes independent neuronal and vascular pathologies in a novel transgenic model
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2012-11-01
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.2841-12.2012
Open Access Status File (Publisher version)
Volume 32
Issue 45
Start page 15715
End page 15727
Total pages 13
Place of publication Washington, DC, United States
Publisher Society for Neuroscience
Language eng
Abstract Müller cells are the major glia of the retina that serve numerous functions essential to retinal homeostasis, yet the contribution of Müller glial dysfunction to retinal diseases remains largely unknown. We have developed a transgenic model using a portion of the regulatory region of the retinaldehyde binding protein 1 gene for conditional Müller cell ablation and the consequences of primary Müller cell dysfunction have been studied in adult mice. We found that selective ablation of Müller cells led to photoreceptor apoptosis, vascular telangiectasis, blood-retinal barrier breakdown and, later, intraretinal neovascularization. These changes were accompanied by impaired retinal function and an imbalance between vascular endothelial growth factor-A (VEGF-A) and pigment epithelium-derived factor. Intravitreal injection of ciliary neurotrophic factor inhibited photoreceptor injury but had no effect on the vasculopathy. Conversely, inhibition of VEGF-A activity attenuated vascular leak but did not protect photoreceptors. Our findings show that Müller glial deficiency may be an important upstream cause of retinal neuronal and vascular pathologies in retinal diseases. Combined neuropro-tective and anti-angiogenic therapies may be required to treat Müller cell deficiency in retinal diseases and in other parts of the CNS associated with glial dysfunction.
Keyword Idiopathic macular telangiectasia
Ciliary neurotrophic factor
Endothelial growth-factor
Juxtafoveolar retinal telangiectasis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
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