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Effect of vascular endothelial growth factor upregulation on retinal gene expression in the Kimba mouse.
- Source :
-
Clinical & experimental ophthalmology [Clin Exp Ophthalmol] 2013 Apr; Vol. 41 (3), pp. 251-62. Date of Electronic Publication: 2012 Oct 17. - Publication Year :
- 2013
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (© 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.)
- Subjects :
- Animals
Betacellulin
Diabetic Retinopathy metabolism
Endothelin-2 metabolism
Enzyme-Linked Immunosorbent Assay
Gene Expression Profiling
Immunohistochemistry
Intercellular Signaling Peptides and Proteins metabolism
Mice
Mice, Transgenic
Orphan Nuclear Receptors metabolism
Real-Time Polymerase Chain Reaction
Retinal Neovascularization metabolism
Semaphorins metabolism
Diabetic Retinopathy genetics
Gene Expression Regulation physiology
Retinal Neovascularization genetics
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1442-9071
- Volume :
- 41
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical & experimental ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 22788671
- Full Text :
- https://doi.org/10.1111/j.1442-9071.2012.02845.x