Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3107-16.

Attenuation of experimental proliferative vitreoretinopathy by inhibiting the platelet-derived growth factor receptor.

Author information

  • 1The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.

Abstract

PURPOSE:

The work from numerous laboratories has led to the idea that the growth factors such as platelet-derived growth factor (PDGF) contribute to proliferative vitreoretinopathy (PVR) in experimental models of the disease, as well as in humans. In support of this idea, the authors have previously reported that cells unable to respond to PDGF had a greatly reduced PVR potential, compared with PDGF-responsive versions of the same cells. The goal of this study was to test the effect of blocking the output of the PDGF receptor in an experimental model of PVR.

METHODS:

Polymerase chain reaction-based site-directed mutagenesis was used to generate point mutations in the human PDGF alpha receptor (alphaPDGFR) cDNA, which resulted in single amino acid substitutions. These changes were based on naturally occurring point mutations in the c-kit receptor tyrosine kinase, which suppresses the function of wild-type c-kit. A truncated alphaPDGFR was also made, in which the receptor ended just after the juxtamembrane domain. As with the point mutants, truncated receptors have been shown to block the action of wild-type receptors. All the alphaPDGFR mutants were introduced into cells that naturally express the wild-type receptor, and the PDGF-dependent output of the resultant cell lines was determined. In addition, the PVR potential of cell lines expressing the mutant receptors was tested in a PVR rabbit model.

RESULTS:

Although the mutants differed in their ability to suppress PDGF-dependent signaling of the wild-type receptor, each mutant effectively blocked cell cycle progression. When expressed in rabbit conjunctival fibroblasts, a cell line that effectively induces PVR, the mutant receptors blocked PVR to various degrees. The most effective receptor was the truncated mutant.

CONCLUSIONS:

These data suggest that the alphaPDGFR plays an important role in PVR. In addition, these mutant receptors appear to have therapeutic potential for prevention of this blinding disease.

PMID:
10967071
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk