[Selective non-peptide CXCR2 antagonist SB225002 inhibits choroidal neovascularization in rat model]

We tested the applicability of using SB225002, a selective non-peptide CXCR2 inhibitor, for inhibiting experimental choroidal neovascularization (CNV) in Brown Norway (BN) rats.

It was an experimental study. CNV was induced in 12 adult BN rats with laser photocoagulation. 10 micromol/L SB225002 was administered into the vitreous of 6 rats right after laser injury. DMSO was used as the control in other 6 rats. Three BN rats were served as non-laser-treated controls in quantitative real-time reverse transcription PCR (qRT-PCR) analysis. Fluorescein angiography was performed on day 7 postoperatively to observe the fluorescein leakage of CNV. Quantitative analysis on choroidal flat mounts was performed to evaluate the area changes of CNV lesions. qRT-PCR analysis was used to compare the changes shown by the SB225002-, DMSO- and non-laser-treated BN rats with regard to mRNA levels of CXCR2 and vascular endothelial growth factor (VEGF) in the RPE-choroidal complex.

SB225002 (10 micromol/L) significantly inhibited the fluorescein leakage (P < 0.05), the extent of neovascularization on choroidal flat mount of rat CNV model was decreased up to 66% (t = 2.54, P = 0.001). CXCR2 and VEGF mRNA were reduced significantly following this treatment (t = 8.54, 3.61; P = 0.007, 0.002).

SB225002 inhibits angiogenic activity of IL-8 by blocking its binding with CXCR2 in the early stage of CNV, which may provide a potential new therapeutic strategy for CNV.