Hepatocyte growth factor stimulates proliferation and migration during wound healing of retinal pigment epithelial cells in vitro.

PURPOSE: A defect in retinal pigment epithelial (RPE) cells may cause dysfunction of the neural retina, so rapid recovery of differentiated RPE cells is required after RPE injury. We investigated the effect of hepatocyte growth factor (HGF) on wound healing in RPE cells. METHODS: Confluent monolayers of bovine RPE cells were denuded, and the cells were allowed to recover in the presence or absence of HGF. The effect of HGF on RPE cell proliferation was evaluated by a 3-(4;5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay. In a migration assay, mitomycin C was used to inhibit proliferation, and the number of migrated cells was counted. The signaling pathways involved were examined using inhibitors of mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 (PI3) kinase and protein kinase C pathways. RESULTS: At 80 ng/mL, HGF stimulated the wound closure of RPE monolayers and rendered the restituted cells more epithelioid in shape. HGF at 10 ng/mL stimulated RPE cell migration the most, whereas 80 ng/mL of HGF inhibited migration, but stimulated proliferation the most. In particular, PI3 kinase and MAPK inhibitor inhibited PRE cell migration and proliferation, respectively. CONCLUSIONS: HGF stimulated wound closure in cultured RPE cells, and rendered restituted cells epithelioid in shape. HGF may become a therapeutic candidate for RPE wound healing.

Effect of travoprost on 24-hour intraocular pressure in normal tension glaucoma.

PURPOSE: The effect of travoprost 0.004% on 24-hour intraocular pressure (IOP) was examined in patients with normal tension glaucoma (NTG). SUBJECTS AND METHODS: This study included 17 patients with newly diagnosed unilateral NTG. IOP was measured at three-hour intervals over 24 hours by Goldman applanation tonometer in patients taking topical travoprost 0.004% and was compared retrospectively with 24-hour IOP data in untreated eyes. RESULTS: IOP values were significantly reduced at individual time points after treatment (P < 0.01). Mean 24-hour IOP, maximum 24-hour IOP, minimum 24-hour IOP, and 24-hour IOP fluctuations at baseline (mean +/- SD) were 12.9 +/- 2.2 mmHg, 15.4 +/- 2.7 mmHg, 10.5 +/- 2.2 mmHg, and 4.9 +/- 1.2 mmHg, respectively, and were significantly reduced to 10.3 +/- 2.0 mmHg, 12.4 +/- 2.5 mmHg, 8.5 +/- 1.9 mmHg (all P < 0.001), and 3.9 +/- 1.5 mmHg (P < 0.05), respectively, after treatment. The rate of IOP reduction greater than 20% was 58.8% (10 eyes) for maximum 24-hour IOP and 53.0% (nine eyes) for mean 24-hour IOP. CONCLUSION: Travoprost reduced IOP throughout the 24-hour study period, with over half of the eyes examined showing IOP reduction exceeding 20%.

Reduction of experimental laser-induced choroidal neovascularization by orally administered BPHA, a selective metalloproteinase inhibitor.

BACKGROUND: N-Biphenyl sulfonyl-phenylalanine hydroxamic acid (BPHA), a synthetic, selective matrix metalloproteinase (MMP)-2, -9, -14 inhibitor, has been reported to show significant antiangiogenic activity without unpleasant adverse effects. After film in situ zymography (FIZ) and conventional zymography were performed to detect MMP in experimental choroidal neovascularizations (CNVs), we studied the reducible effect of BPHA on CNVs. METHODS: Using FIZ, the gelatinolytic activity of MMPand BPHA-reduction on gelatinolysis were examined in diode-laser-induced CNV lesions in a total of 22 male Brown Norway rats. The MMP subtypes were studied in the CNV lesions of three rats using conventional zymography. Vehicle solution only or 25-, 50-, or 100 mg/kg-body-weight of BPHA was administered orally twice daily for 14 days after the laser photocoagulation in 18 rats, respectively. Fluorescein angiograms were taken, and the late hyperfluorescence of CNVs was given scores by three researchers using four grades. The thickness of CNV lesions was studied histologically. RESULTS: In laser-induced CNVs, the gelatinolytic activity of MMP and reduction of gelatinolysis by BPHA were observed on FIZ, and MMP-2 and proMMP-2 were identified by conventional zymography. The scores given to the late dye leakage and staining on angiograms were lower in the BPHA-treated groups ( p<0.01) than in the controls, and the effect appeared to be dose-dependent. Similarly, the CNV lesions in the BPHA-treated groups were less thick than in the controls ( p<0.01). CONCLUSIONS: MMP-2 played a role in laser-induced CNV development, and administration of BPHA reduced the experimental CNVs.