November 1996
Volume 37, Issue 12
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Articles  |   November 1996
Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas.
Author Affiliations
  • L W Reneker
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • P A Overbeek
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Investigative Ophthalmology & Visual Science November 1996, Vol.37, 2455-2466. doi:
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      L W Reneker, P A Overbeek; Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas.. Invest. Ophthalmol. Vis. Sci. 1996;37(12):2455-2466.

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Abstract

PURPOSE: To investigate the possibility that platelet-derived growth factor (PDGF) might regulate aspects of mouse retinal development in vivo. METHODS: In situ hybridization was used to study the expression patterns of PDGF-A and PDGF-B and their receptors during normal mouse eye development. Transgenic mice that express human PDGF-A in the lens under the control of alpha A-crystallin promoter were generated by pronuclear microinjection. The effects of PDGF overexpression on eye development were analyzed by ocular histology, immunohistochemistry and in situ hybridizations. RESULTS: The PDGF genes are expressed by cells in close contact with retinal astrocytes. The PDGF-A messenger RNA is upregulated in the retinal ganglion neurons after birth, and PDGF-B is expressed by the blood vessel cells in the hyaloid vasculature. The authors found that lens-specific expression of PDGF-A in the eye can induce hyperplasia of retinal astrocytes, which express PDGF-alpha receptor (PDGF-alpha R) during development. The retinal alterations in the PDGF-A transgenic mice closely resemble the retinal astrocytic hamartomas found in human tuberous sclerosis (TSC) disease. CONCLUSIONS: These findings suggest that proliferation of retinal astrocytes is regulated by PDGF during normal eye development. The authors speculate that proliferation of retinal astrocytes is mediated through a PDGF signaling pathway, which may involve the TSC gene product.

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