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Michael C. Briggs, Ian Grierson, Paul Hiscott, John A. Hunt; Active Scatter Factor (HGF/SF) in Proliferative Vitreoretinal Disease. Invest. Ophthalmol. Vis. Sci. 2000;41(10):3085-3094.
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purpose. Hepatocyte growth factor/scatter factor (HGF/SF) possesses mitogenic,
motogenic, and morphogenic properties and has recently been implicated
in various retinal diseases. The role of HGF/SF in proliferative
vitreoretinal disease was investigated.
methods. Sections of epiretinal membranes were stained immunohistochemically for
cytokeratins, to identify HRPE cells, and for HGF/SF receptor (c-Met).
Cultured HRPE cells were stained for c-Met and investigated for shape
change in response to HGF/SF, by using image analysis. The
dose–response relationship for HRPE cells to HGF/SF was investigated
by a cell migration assay and the specificity of this response
evaluated by a neutralization experiment. Subretinal fluid (SRF) and
vitreous from patients with retinal detachment and proliferative
vitreoretinopathy (PVR) plus vitreous from eyes obtained after death,
eyes with macular hole, and eyes with proliferative diabetic
retinopathy (PDR) were investigated for the presence of HGF/SF using an
enzyme-linked immunosorbent assay (ELISA). HGF/SF activity was measured
using an MDCK cell scatter assay.
results. HRPE cells in epiretinal membranes and in culture expressed c-Met.
Cultured HRPE cells responded to HGF/SF by an epithelial-to-mesenchymal
shape change and by cell migration, a response that increased with
increasing concentrations of HGF/SF. This response was reduced in the
presence of neutralizing antibody. There was evidence of HGF/SF in
increasing concentrations in more severe PVR and in PDR when measured
by ELISA, and, conversely, there was evidence of correspondingly
decreasing HGF/SF activity when measured by MDCK cell scatter assay in
conclusions. HGF/SF is present in normal and pathologic vitreous. HRPE cells respond
by shape change and cell migration to HGF/SF. Concentrations of HGF/SF
increase in proliferative vitreoretinal disease and increase in turn
with increased severity of the disease, but HGF/SF bioactivity
decreases (consistent with activator depletion). These findings are
consistent with the hypothesis that HGF/SF may play a role in the HRPE
mesenchymal transformation that typifies PVR.
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