Abstract
Purpose: :
To investigate the inhibiton of trehalose on angiogenesis and fibrosis.
Methods: :
Normal human dermal fibroblasts (NHDF) and umbilical vein endothelial cells (HUVEC) were co-cultured in trehalose-containing medium (10.0/7.5/5.0/2.5%) with or without VEGF.After 11 days, we evaluated each of area, length, joint and path of neovascularization with immunohistochemistry using anti-CD31 antibody.In addition, we generated alkali-burn induced corneal neovascularization in Balb/c mice. After placing filter paper (1.5mm in diameter) presoaked in 1N NaOH on cornea of one eye of each animal for 60s, we divided mice into 4 groups (2.5/ 5.0/ 7.5% trehalose eye drop/ 0.9% saline eye drop group).After injecting fluorescein-isothiocyanate-dextran at 14 days after treatment, we enucleated eye balls and made corneal flatmounts to quantify corneal neovascularization.
Results: :
In in vitro model, the proliferation of HUVEC concerning area, length, joint and path of newly formed vessels was inhibited by trehalose by dose-dependent manner.In in vivo model, corneal neovascularization was strongly inhibited by trehalose eye drops more than 5%.
Conclusions: :
Trehalose is a disaccharide, and isomer of sucrose. The osmotic pressure of 5% trehalose medium is identical with 0.9% saline solution.We previously reported the inhibitory effects of trehalose on proliferation of fibroblasts. In this study, we demonstrate the possibility that trehalose inhibits not only fibrosis but also angiogenesis.The present study suggests that the possibility that trehalose has a potential to be used as a therapeutic agent to minimize fibrosis and/or neovascularization in the future.
Keywords: wound healing • neovascularization • proliferation