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Active scatter factor (HGF/SF) in proliferative vitreoretinal disease
M C Briggs1, I Grierson, P Hiscott
1St. Paul's Eye Unit, Royal Liverpool University Hospital, UK. mcbriggs@aol.com
Investigative Ophthalmology & Visual Science
|September 1, 2000
Summary
Hepatocyte growth factor/scatter factor (HGF/SF) drives retinal cell changes in proliferative vitreoretinal diseases. While HGF/SF concentration increases with disease severity, its activity paradoxically decreases, suggesting a complex role in PVR.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Hepatocyte growth factor/scatter factor (HGF/SF) has known mitogenic, motogenic, and morphogenic properties.
- HGF/SF has been implicated in the pathogenesis of various retinal diseases.
- Its specific role in proliferative vitreoretinal disease requires further investigation.
Purpose of the Study:
- To investigate the role of HGF/SF in proliferative vitreoretinal disease.
- To determine if HGF/SF influences human retinal pigment epithelial (HRPE) cells.
Main Methods:
- Immunohistochemical staining of epiretinal membranes for cytokeratins and HGF/SF receptor (c-Met).
- Assessment of HRPE cell shape change and migration in response to HGF/SF using image analysis and cell migration assays.
- Quantification of HGF/SF concentration and activity in patient vitreous and subretinal fluid using ELISA and MDCK cell scatter assays.
Main Results:
- HRPE cells express c-Met and undergo epithelial-to-mesenchymal transition and migration in response to HGF/SF.
- HGF/SF concentrations were elevated in more severe proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR).
- HGF/SF bioactivity decreased in these conditions, despite increased concentrations.
Conclusions:
- HGF/SF is present in normal and pathological vitreous.
- HRPE cells are responsive to HGF/SF, exhibiting shape change and migration.
- Elevated HGF/SF concentrations with decreased bioactivity in proliferative vitreoretinal diseases suggest a role in HRPE mesenchymal transformation characteristic of PVR.