Chemical Injury-Induced Corneal Opacity and Neovascularization Reduced by Rapamycin via TGF-β1/ERK Pathways Regulation

作者：Young Joo Shin, Joon Young Hyon, Won Seok Choi, Kayoung Yi, Eui‐Sang Chung, Tae-Young Chung, Won Ryang Wee · 发表于：Investigative Ophthalmology & Visual Science · 年份：2013 · DOI：10.1167/iovs.13-11684 · 被引用次数：70 · 研究领域：Corneal Surgery and Treatments、Corneal surgery and disorders、Ocular Surface and Contact Lens

PURPOSE: To investigate the protective effect of rapamycin against alkali burn-induced corneal damage in mice. METHODS: BALB/c mice were treated with 0.1 N NaOH to the cornea for 30 seconds. Corneal neovascularization and opacity were clinically evaluated at 1, 2, and 4 weeks after chemical burn injury. Rapamycin was delivered topically to right eyes (1 mg/mL) and injected intraperitoneally (0.2 mg/kg) once a day. Concentrations of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-β1) in the cornea were measured by enzyme-linked immunosorbent assay (ELISA). In vitro-cultured human corneal stromal cells were treated with 0 to 500 nM rapamycin for 3 days and then assessed by immunofluorescence staining of vimentin and alpha-smooth muscle actin (α-SMA). Western blotting assays for α-SMA, phosphorylated extracellular signal-regulated kinase (ρ-ERK 1/2), and total ERK 1/2 were also performed. RESULTS: Corneal neovascularization and corneal opacity scores measured 4 weeks after the chemical burn corneal injury were lower in the rapamycin group than in the control group. Two weeks after the chemical burn injury, a significant elevation in the corneal IL-6 levels of the positive control group was observed, compared to the levels in the negative control group or the rapamycin group (P < 0.05). Corneal TGF-β1 levels were lower in the rapamycin-treated group than in the control group at 4 weeks after chemical burn injury (P < 0.05). Moreover, rapamycin inhibited TGF-β1-indu...