Hepatocyte growth factor receptor in human RPE cells: implications in proliferative vitreoretinopathy.
OBJECTIVE
To determine whether hepatocyte growth factor (HGF) receptor (HGFR) is expressed in retinal pigment epithelial (RPE) cells and to test whether RPE cells are responsive to HGF. To evaluate expression of HGFR in human donor eyes and in several epiretinal membranes associated with proliferative vitreoretinopathy and idiopathic epiretinal membranes.


METHODS
HGF-dependent migration and proliferation in primary and simian virus (SV) 40-transformed human RPE cells was studied using a Boyden chamber and [3H]thymidine uptake, respectively. The expression and tyrosine phosphorylation of HGFR protein was evaluated in RPE cells by immunoprecipitation and western blot analysis. Expression of HGFR in human donor eyes and in several epiretinal membranes associated with proliferative vitreoretinopathy (PVR) and idiopathic epiretinal membranes was analyzed by immunohistochemistry.


RESULTS
HGFR was expressed in RPE cells and was tyrosine-phosphorylated in response to HGF. Whereas HGF was a potent motogen for RPE cells, it induced only a modest, dose-dependent uptake of [3H]thymidine. Evaluation of human donor eyes showed that the RPE monolayer was the major cell type that was strongly positive for HGFR. HGFR was uniformly and readily detected in the cellular component of epiretinal membranes associated with PVR, whereas little or no HGFR was found in idiopathic epiretinal membranes.


CONCLUSIONS
HGFR is expressed in cultured RPE cells, in the RPE monolayer in human donor eyes, and in epiretinal membranes obtained from patients with PVR. Furthermore, HGF is a potent chemoattractant for cultured human RPE cells. These observations suggest a role for HGF and HGFR in normal function of RPE cells and in RPE-related disease such as PVR.
Lashkari
K
K
The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Rahimi
N
N
Kazlauskas
A
A
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008566:Membranes / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013539:Simian virus 40; D014443:Tyrosine; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology
D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met