Inhibiting effect of celecoxib intravitreal injection on choroidal neovascularization in a rat model / 眼科研究

ABSTRACT

Objective Our previous study showed that cycloxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are expressed in choroidal neovascularization (CNV) and the expression of COX-2 is prior to VEGF, indicating that COX-2 is probably one of upstream regulatory factors of VEGF. The aim of this study was to observe inhibition and mechanism of intravitreous injection of celecoxib, a selective COX-2 inhibitor, on experimental choroidal neovascularization in a laser-induced rat model. Methods Retinal photocoagulation was performed in 36 right eyes of 36 male Brown Norway rats to establish CNV models with the laser parameter as followswavelength 532 nm, power 80 mW, spot diameter 100 p, m and time shutter 100 ms. Eight or ten spots were irradiated in the position of 1.5 - 2. 0 PD to optic disc. Celecoxib or normal saline solution was intravitreously injected via scleral incision in 18 right eyes of 18 rats, respectively. The thickness and area of CNV were qualified by HE staining(n =3) and by choroidal flatmount (n =3) at day 14 after photocoagulation under the light microscope. The expressions of VEGF and COX-2 in RPE-choroid-sclera complex were examined by Western blot(n =6) and RT-PCR(n =6) at day 7 after photocoagulation. The experimental procedure followed the Standard of Association for Research in Vision and Ophthalmology. The license for animal administration was obtained. Results After intravitreous injection with celecoxib, the thickness and area of CNV were significantly smaller in celecoxib group than normal saline group on 14 days (69. 75 μm ± 7. 50 μm vs 45. 84 μm ± 5. 59 μm in thickness and 87 854 pixel~2 ± 6 735 pixel~2 vs 61 101 pixel~2 ± 6 314 pixel~2 in area, P =0.00). The expressions of VEGF protein and mRNA were obviously lower in celecoxib group compared with normal saline group(t = 3. 755, P = 0.02; t =3. 155, P =0. 03) . No significant difference was found in expression of COX-2 mRNA between the two groups (t = 0. 581, P = 0. 59). Conclusion Intravitreous injection of celecoxib can effectively inhibit CNV by downregulating VEGF level, which is a new approach for the treatment of CNV.