Lens-specific expression of PDGF-A in transgenic mice results in retinal astrocytic hamartomas.
OBJECTIVE
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.
Reneker
L W
LW
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Overbeek
P A
PA
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D002455:Cell Division; D003459:Crystallins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006222:Hamartoma / Q000209:etiology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012164:Retinal Diseases / Q000209:etiology* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
D003459:Crystallins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D011505:Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor