Purchase this article with an account.
D. Huang, Y. Li, L. Luo, C. Liang, R. Wen; Inhibition of Choroidal Neovascularization (CNV) by X-82 in a Subretinal Matrigel CNV Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2966.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have developed a subretinal Matrigel CNV (choroidal neovascularization) model to mimic the pathological conditions in "wet" age-related macular degeneration in human. In the present work, we investigated the potential of X-82, a dual VEGFR/PDGFR inhibitor, in CNV inhibition using the Matrigel CNV model.
CNV was induced by injecting Matrigel (growth factor depleted, 3:1 dilution with PBS, 1.2 µl/eye) into the subretinal space in adult female Sprague-Dawley rats. The experiment had two control groups: a 10-day control group with an endpoint of 10 days after Matrigel injection and a 20-day control group, with an endpoint of 20 days after Matrigel injection. The 20-day control group was treated with vehicle orally from 10 days after Matrigel injection. For treatment, X-82 was dissolved in vehicle at a concentration of 20 mg/ml and administered orally. Animals were treated once daily with either 10 mg/kg (X-82-10mg group) or 30 mg/kg (X-82-30mg group). Treatment started 10 days and ended 20 days after Matrigel injection. By the end points, animals were killed by CO2 overdose and perfused with a DiI solution (Li et al, Nature Protocols, 2008). Serial vibratome sections were cut throughout the Matrigel injected area of each eye and examined by fluorescence microscopy. CNV invaded area of each eye was measured and calculated.
CNV was observed in all eyes collected. CNV invaded area in the 10-day control group is 282.40±99.20 (1,000 µm2, mean±SD, n=7). The CNV area in the 20D control group is 1,326.95±583.71 (n=6). The 3.7-fold increase in CNV invaded area between 10-day and 20-day control groups demonstrates the progressive nature of CNV of this model. In comparison, the treated groups have significantly smaller CNV areas than the 20-day control group. The X-82-10mg group had an average CNV area of 493.58±317.17 (n=6) (p=0.012, compared to 20-day controls), whereas the CNV area of the X-82-30mg group is 357.70±267.97 (n=6) (p=0.0043, compared to 20-day controls).
Oral administration of the VEGFR/PDGFR inhibitor X-82 at either 10 or 30 mg/kg significantly inhibits CNV progression in the subretinal Matrigel CNV model.
This PDF is available to Subscribers Only