{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:23Z","timestamp":1760120063833},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,10,17]],"date-time":"2012-10-17T00:00:00Z","timestamp":1350432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>A<jats:sc>bstract<\/jats:sc><\/jats:title><jats:p><jats:bold>Background:\u2002<\/jats:bold> 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.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Retinal gene expression changes in juvenile and adult Kimba mice were assayed by microarray and compared with age\u2010matched wild\u2010type littermates. Transcription of selected genes was validated by quantitative real\u2010time polymerase chain reaction. Protein translation was determined using immunohistochemistry and enzyme\u2010linked immunosorbent assay.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> 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 M\u00fcller cells of Kimba retinae at greater signal intensities than in wild type. Endothelin 2 colocalised to M\u00fcller 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 M\u00fcller cell somata.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> An early spike in vascular endothelial growth factor induced significant long\u2010term retinal neovascularisation associated with changes to the retinal ganglion, photoreceptor and M\u00fcller 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.<\/jats:p>","DOI":"10.1111\/j.1442-9071.2012.02845.x","type":"journal-article","created":{"date-parts":[[2012,7,13]],"date-time":"2012-07-13T08:25:47Z","timestamp":1342167947000},"page":"251-262","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of vascular endothelial growth factor upregulation on retinal gene expression in the Kimba mouse"],"prefix":"10.1111","volume":"41","author":[{"given":"Nicolette","family":"Binz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ireni S","family":"Ali Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly 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