Effect of vascular endothelial growth factor upregulation on retinal gene expression in the Kimba mouse

Binz, Nicolette, Ali, Rahman Ireni S., Chinnery, Holly R., McKeone, Richard, Simpson, Ken M., Speed, Terence P., Lai, Chooi-May and Rakoczy, P. Elizabeth 2013, Effect of vascular endothelial growth factor upregulation on retinal gene expression in the Kimba mouse, Clinical and experimental ophthalmology, vol. 41, no. 3, pp. 251-262, doi: 10.1111/j.1442-9071.2012.02845.x.

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Title Effect of vascular endothelial growth factor upregulation on retinal gene expression in the Kimba mouse
Author(s) Binz, Nicolette
Ali, Rahman Ireni S.
Chinnery, Holly R.
McKeone, Richard
Simpson, Ken M.
Speed, Terence P.
Lai, Chooi-May
Rakoczy, P. Elizabeth
Journal name Clinical and experimental ophthalmology
Volume number 41
Issue number 3
Start page 251
End page 262
Total pages 12
Publisher Blackwell Science Asia
Place of publication Melbourne, Vic.
Publication date 2013
ISSN 1442-6404
Keyword(s) diabetic retinopathy
retinal architecture
Summary Background:  The Kimba mouse carries a human vascular endothelial growth factor transgene causing retinal neovascularisation similar to that seen in diabetic retinopathy. Here, we examine the relationship between differential gene expression induced by vascular endothelial growth factor overexpression and the architectural changes that occur in the retinae of these mice.

Methods:  Retinal gene expression changes in juvenile and adult Kimba mice were assayed by microarray and compared with age-matched wild-type littermates. Transcription of selected genes was validated by quantitative real-time polymerase chain reaction. Protein translation was determined using immunohistochemistry and enzyme-linked immunosorbent assay.

Results:  Semaphorin 3C was upregulated, and nuclear receptor subfamily 2, group 3, member 3 (Nr2e3) was downregulated in juvenile Kimba mice. Betacellulin and endothelin 2 were upregulated in adults. Semaphorin 3C colocalized with glial fibrillary acidic protein in Müller cells of Kimba retinae at greater signal intensities than in wild type. Endothelin 2 colocalised to Müller cell end feet and extended into the outer limiting membrane. Endothelin receptor type B staining was most pronounced in the inner nuclear layer, the region containing Müller cell somata.

Conclusions:  An early spike in vascular endothelial growth factor induced significant long-term retinal neovascularisation associated with changes to the retinal ganglion, photoreceptor and Müller cells. Overexpression of vascular endothelial growth factor led to dysregulation of photoreceptor metabolism through differential expression of Nr2e3, endothelin 2, betacellulin and semaphorin 3C. Alterations in the expression of these genes may therefore play key roles in the pathological mechanisms that result from retinal neovascularisation.
Language eng
DOI 10.1111/j.1442-9071.2012.02845.x
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2013, Blackwell Science Asia
Persistent URL http://hdl.handle.net/10536/DRO/DU:30052118

Document type: Journal Article
Collection: School of Medicine
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