Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas.

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.