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A. Ohlmann, M. Scholz, E. R. Tamm; Elevated TGF-ß1 Signaling in Transgenic Mice Inhibits Development of the Choroidal Vasculature. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1225.
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To study the influence of TGF-ß1 signaling on the development of the choroidal vasculature.
Transgenic mice with lens expression of active TGF-ß1 under control of the strong ßB1-crystallin promoter (Flügel-Koch et al., Dev. Dyn. 2002) were bred in a FVB/N or mixed FVB/N x CD31 background. The retinal and choroidal phenotypes of heterozygous ßB1-TGFß1 mice were investigated from postnatal day (P) 0 to P21 by light and electron microscopy, by staining with biotinylated Griffonia simplicifolia lectin, immunostaining for GFAP, α-smooth muscle actin, Thy-1, p-Smad2/3 and activated caspase-3, and by TUNEL labeling.
The enhanced expression of TGF-ß1 during eye development results in inhibition of choridal vascular growth as ßB1-TGFß1 mice do not develop a layer of choriocapillares underlying the outer retina. In addition, no capillaries develop in the plexiform layers of the retina. When compared to wild-type littermates, retinal neurons of ßB1-TGFß1 mice show a significant increase of apoptotic cell between P7 and P9. A second peak of apoptotic cell death is observed around P14, when apoptosis is mainly found in the outer nuclear layer. Comparable findings were seen when mice with FVB/N were compared with those with mixed FVB/N x CD31 background, in which wild-type littermates develop a normal retinal phenotype.
In transgenic in vivo conditions, TGF-ß1 signaling inhibits growth of retinal and choroidal capillaries. The lack of capillaries leads to an increase in apoptotic cell death of retinal neurons.
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