Netrin-1 simultaneously suppresses corneal inflammation and neovascularization
Journal
Investigative Ophthalmology and Visual Science
Journal Volume
53
Journal Issue
3
Pages
1285-1295
Date Issued
2012
Author(s)
Abstract
PURPOSE. To investigate the effect of netrin-1 on alkali burninduced corneal inflammation and neovascularization. METHODS. The expression of netrin-1 and its receptors UNC5A, UNC5B, UNC5C, UNC5D, adenosine 2b receptor (A2BAR), deleted in colorectal cancer (DCC), and neogenin in normal and alkali-burned rat cornea were determined by RT-PCR and/or Western blot analysis, or immunostaining. Topical netrin-1 protein was applied to treat rat corneal alkali-burn injury for 14 consecutive days, started right after the injury or 10 days postinjury. Corneal inflammation and neovascularization were observed under slit lamp microscope. The apoptosis of corneal cells was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Corneal inflammatory cell infiltration was evaluated by immunostaining of anti-PMN and anti-ED1 antibodies. The expression of epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), and pigment epithelium-derived factor (PEDF) in rat cornea was determined by Western blot analysis. RESULTS. Netrin-1 and its receptor UNC5B were expressed in normal rat corneal epithelium and stromal cells, and their expression decreased after corneal alkali burn. Exogenous netrin- 1 administered on rat ocular surfaces resolved alkali burninduced corneal inflammation, and also suppressed corneal neovascularization. Furthermore, netrin-1 could reverse neovascularization in alkali-burned cornea. The authors found that netrin-1 executed the functions through various mechanisms, including upregulating EGF expression, accelerating epithelial wound healing, inhibiting neutrophil and macrophage infiltration, reducing corneal cell apoptosis, and restoring the equilibrium of VEGF and PEDF in the wounded cornea. CONCLUSIONS. Netrin-1 could dampen inflammation, inhibit, and reverse neovascularization in alkali-burned cornea. ? 2012 The Association for Research in Vision and Ophthalmology, Inc.
SDGs
Other Subjects
adenosine A2b receptor; epidermal growth factor; messenger RNA; neogenin; netrin 1; pigment epithelium derived factor; receptor; unc5a receptor; unc5b receptor; unc5c receptor; unc5d receptor; unclassified drug; vasculotropin; Drosophila protein; eye drops; nerve growth factor; netrin 1; netrin-1; RNA; tumor suppressor protein; animal experiment; animal model; animal tissue; apoptosis; article; caustic burn; cell infiltration; controlled study; cornea edema; cornea injury; cornea neovascularization; gene expression; immunohistochemistry; keratitis; male; nick end labeling; nonhuman; priority journal; protein expression; rat; reverse transcription polymerase chain reaction; scar formation; slit lamp; Western blotting; wound healing; animal; biosynthesis; comparative study; disease model; drug effect; gene expression regulation; genetics; keratitis; metabolism; pathology; real time polymerase chain reaction; Wistar rat; Animals; Apoptosis; Blotting, Western; Corneal Neovascularization; Disease Models, Animal; Drosophila Proteins; Gene Expression Regulation; Keratitis; Male; Nerve Growth Factors; Ophthalmic Solutions; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA; Tumor Suppressor Proteins
Type
journal article