Article
The Norrie Disease Protein (NDP) is a growth factor for retinal neurons and capillaries in vivo
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Published: | September 22, 2004 |
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Outline
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Objective
Mutations in the Norrie disease protein (NDP) are causative for Norrie disease characterized by congenital blindness. Mice with a targeted disruption of NDP suffer from a continuous loss of retinal ganglion cells and a deficient vascularization of the outer retina. In previous studies, a role of NDP as growth factor has been suggested.
Methods
Four transgenic mouse lines were developed that overexpress NDP in the eye under control of the lens specific (beta)B1-crystallin promoter. The phenotype of transgenic mice was investigated from E14 to P28. A specific peptide antibody against NDP was generated to perform western blot analysis and immunohistochemistry.
Results
By northern and western blot analyses as well as by immunohistochemistry, a strong signal for NDP was observed in lenses of transgenic mice. At P2, central and peripheral retina was obviously thicker in transgenic mice than in control littermates. This was due to a 50% increase of retinal ganglion cells (RGS) and a 28% increase of nuclear layer neurons (NLN). In the peripheral retina, RGS increased by 79% and NLN by 62%. The differences were statistically significant (p<0.05). Transgenic mice had significantly more hyaloid capillaries at the posterior lens and an overexpression of VEGF and PLGF. In vitro, lenses of transgenic mice induce proliferation in cultured human endothelial capillary cells. When NDP overexpressing mice were crossbred with NDP deficient mice, the phenotype of NDP deficient mice was completely rescued.
Conclusions
NDP has a growth stimulatory effect on retinal neurons and ocular capillaries.
Supported by the Glaucoma Research Foundation, San Francisco, CA and the SFB 539