PMID- 10967068
OWN - NLM
STAT- MEDLINE
DCOM- 20000914
LR  - 20091119
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 41
IP  - 10
DP  - 2000 Sep
TI  - Active scatter factor (HGF/SF) in proliferative vitreoretinal disease.
PG  - 3085-94
AB  - 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 these diseases. 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.
FAU - Briggs, M C
AU  - Briggs MC
AD  - St. Paul's Eye Unit, Royal Liverpool University Hospital, UK. mcbriggs@aol.com
FAU - Grierson, I
AU  - Grierson I
FAU - Hiscott, P
AU  - Hiscott P
FAU - Hunt, J A
AU  - Hunt JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 68238-35-7 (Keratins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cell Size/drug effects
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epiretinal Membrane/metabolism
MH  - Hepatocyte Growth Factor/*metabolism/pharmacology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Keratins/metabolism
MH  - Kidney/metabolism
MH  - Middle Aged
MH  - Pigment Epithelium of Eye/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-met/metabolism
MH  - Retinal Detachment/metabolism
MH  - Vitreoretinopathy, Proliferative/*metabolism
MH  - Vitreous Body/metabolism
EDAT- 2000/09/01 11:00
MHDA- 2000/09/19 11:01
CRDT- 2000/09/01 11:00
PHST- 2000/09/01 11:00 [pubmed]
PHST- 2000/09/19 11:01 [medline]
PHST- 2000/09/01 11:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3085-94.