Hepatocyte Growth Factor In Prollferatlve Vitrcorehnopathy

AIM: This study consisted of three parts: To examine the effect of HGF on proliferation and migration of cultured human RPE cells; (2) To determine the concentration of HGF in the vitreous of patients with PVR or proliferative diabetic retinopathy (PDR); (3) To investigate the expression of HGFR in epiretinal membranes (ERM) of eyes with PVR and cultured RPE cells.METHODS: Human RPE cells in serum-starved medium in culture were treated with HGF. Then, MTT assay was used to examine the growth of the cells; an in vitro wound-healing model was used to determine the effects of HGF in RPE migration. ?The high sensitive sandwich enzyme immunoassay technique (ELISA) was used to measure the level of HGF in vitreous of normal group, PVR group, and PDR group. (3) The immunohistochemical technique was used to evaluate the expression of HGFR in human epiretinal membranes complicated with PVR which were obtained from eyes undergone vitrectomy and in cultured RPE cells.RESULTS: HGF(10Mg L,50Hg lOOPg ) increased proliferation rates of cultured human RPE(18.2%, 34.8% and 26.3%, respectively) compared to that of controls (p<0.05 or p<0.01). At a concentration of 50 Mg ?L"1 on day 3 , HGF-7-induced the maximal increase of proliferation (PO.01) ; HGF showed effects on migration of 9.3%, 113.6%, 91.7% and 50.3% at the concentrations of 2 Mg ?I/1,10 Mg ?L"',50 Pg ?L"1 and lOOMg ?L"1, respectively. HGF stimulated the strongest migratory response in RPE cells on a concentration of 10 Mg ?L"1 (113.6%). (2) The mean value of HGF level in the vitreous was 3.34Mg ?L"1 (range 1.82Mg ?L~'~7.38Pg ?L"1) in normal group, 7.4lPg ?L"1 ( range 3.79Hg ?L''~12.8lMg ?L'1 ) in PVR-A,B group, 11.99Mg ?L'1 ( range 7.66Pg ?L~'~20.14ug ?L'1 ) in PVR-C group, 15.55Pg ?L"1 (range 10.34Pg ?L"'~24.56Mg ?L"1) in PVR-D group. In the PDR group, the mean value of HGF in the vitreous was 17.20Mg ?L'1 (range 10.54Hg ?L"'~33.36Mg ?L'1). HGF level in PVR group and PDR group were significantly higher than that in normal group (PO.01); PVR-C, D group and PDR group showed a higher mean vitreous HGF concentration than those in PVR-A, B group (PO.OSor PO.01); The levels of HGF in PVR-D group and PDR group were also higher than those in PVR-C group (PO.05) and there was a significant difference between PDR group and PVR group. As the development of PVR, a progressive increases was seen in the amount of HGF from grade A, B PVR to grade D PVR. ?In 6 membranes of PVR-grade C, HGFR was expressed in 5(83.3%); And in 7 cases it was detected in 9 membranes of PVR-grade D (77.8%). No significant differences were found between PVR-grade C and PVR-grade D in expression of HGFR (P>0.05). The expression of HGFR was detected readily in RPE cells.CONCLUSIONS: HGF can induce the proliferation and marked migration of RPE cells. HGF was a mitogen and potent migratory factor for human cultured RPE cells. (2) HGF levels in the vitreous complicated with PVR or PDR are significantly higher than that in normal group. (3) The expression of HGF in epiretinal membranes and cultured RPE cells indicate that HGF might be involved in epiretinal membranes. Our results indicate that HGF might be involved in the formation and development of epiretinal membranes in PVR and may play a role in the pathogenesis of PVR.