Abstract
BackgroundChoroidal neovascularization (CNV) is a leading cause of central vision loss complicated with age-related macular degeneration. Although intravitreal anti-VEGF therapy is widely used in wet age-related macular degeneration, optimal treatment regimens for the disease are still under investigation. EphrinB2 and EphB4 regulate angiogenesis, and interruption of EphB4/ephrinB2 has been demonstrated to inhibit angiogenesis. In the current study, we studied the effects of soluble EphB4 (sEphB4) on laser induced CNV in a rat model by intravitreous injection and the underlying mechanism.MethodsMale rats (Brown-Norway) were used in the study. CNV was induced by laser and the sEphB4 was injected intravitreous after laser at days 3 and 7. The CNV lesions were evaluated by three methods: fluorescein angiography (FA) in vivo, CNV volume by confocal analysis of choroidal flat-mounts and H&E staining. The expression of fibronectin (FN), VEGFR-2, phospho-VEGFR-2 (pVEGFR-2), the double labeling of EphB4 with FN was analyzed by immunofluorescence. The interaction of FN with EphB4 and the effects of intraocular injection of sEphB4 on the inhibition of pVEGFR-2 were determined by western blot.ResultsThe FA leakage and CNV volume were significantly inhibited by the injection of the sEphB4. Further, histology analysis showed that CNV lesion was significantly smaller in the rats with sEphB4 injection than rats with placebo application. The expressions of pVEGFR-2 and FN in the CNV lesions were reduced compared with controls.ConclusionsOur study suggests that the inhibition of CNV by sEphB4 may be through suppression of VEGFR-2 phosphorylation and the expression of FN. sEphB4 may be a new potential therapeutic strategy of CNV.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.