Inhibition of mouse alkali burn induced-corneal neovascularization by recombinant adenovirus encoding human vasohibin-1
Autor: | Shi-you, Zhou, Zhao-lian, Xie, Ou, Xiao, Xiao-ru, Yang, Boon Chin, Heng, Yasufumi, Sato |
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Rok vydání: | 2010 |
Předmět: |
Recombination
Genetic Vascular Endothelial Growth Factor A Mice Inbred BALB C Vascular Endothelial Growth Factor Receptor-1 Cell Cycle Proteins Genetic Therapy Alkalies Vascular Endothelial Growth Factor Receptor-2 eye diseases Adenoviridae Cornea Mice Gene Expression Regulation Burns Chemical Animals Humans Corneal Neovascularization sense organs Injections Intraocular Conjunctiva Research Article |
Zdroj: | Molecular Vision |
ISSN: | 1090-0535 |
Popis: | Purpose To evaluate the activity of recombinant adenovirus encoding human vasohibin-1 (Ad-Vasohibin-1) on mouse corneal neovasularization induced by alkali burn. Methods For the treatment group, 50 mice each received subconjunctival injection (5 μl) of 109 plaque forming units of replication-defective Ad-Vasohibin-1. Control group mice received the same dosage of blank adenoviral vector (AdNull). Five days after injection, corneal neovascularization (CNV) was induced by placing 2.5 μl of 0.1 M NaOH on the right cornea for 30 s. Subsequently, CNV was observed and photographed every 3 days for a total duration of 9 days after the alkali burn. The percentage of neovascularized area was measured and compared with the AdNull control. The expression of human vasohibin-1 protein was detected by immunohistochemistry and western blotting at 5, 8, and 14 days after injection. The mRNA expression levels of murine vascular endothelial growth factor (Vegf), VEGF receptor 1 and 2 (Vegfr1, Vegfr2), and vasohibin-1 (Vash1) were analyzed and compared by real time quantitative reverse-transcription polymerase chain reaction. Results The percentage of neovascularized area within the cornea was significantly reduced in mice treated with Ad-Vasohibin-1 compared to mice treated with AdNull at every time point after alkali-induced injury (7.11%±3.91% and 15.48%±1.79% of corneal area in the treatment and control groups, respectively, on day 3; 31.64%±4.71% and 43.93%±6.15% on day 6, and 45.02%±9.98% and 66.24%±7.17% on day 9, all p0.05 for both). Conclusions Subconjunctival injection of Ad-Vasohibin-1 significantly reduces corneal neovascularization in alkali-treated mouse corneas. This effect of anti-neovascularization may be related to the downregulation of Vegfr2 expression. |
Databáze: | OpenAIRE |
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