Rofecoxib inhibits retinal neovascularization via down regulation of cyclooxygenase-2 and vascular endothelial growth factor expression.

Abstract

To explore the anti-angiogenesis mechanism of Rofecoxib and determine whether Rofecoxib can be a therapeutic agent for the prevention of retinal neovascularization using a model of retinopathy of prematurity (ROP). ROP was induced by exposing mice to 75% oxygen from postnatal day 7 (P7 ) to P12 , then to room air from P12 to P17 . Sixteen mice were in each of the three groups: untreated ROP group as positive control, Rofecoxib-treated ROP group and the normal group (age-matched mice maintained in room air from birth to P17 as negative control). The localized expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) protein and mRNA in retinal blood vessels was assessed using immunohistochemistry, Western blot analysis and reverse transcription polymerase chain reaction. Mice in the Rofecoxib-treated group had a significantly reduced retinal neovascular tufts compared with those in the untreated ROP group. COX-2 and VEGF protein and mRNA expression levels were increased in the untreated ROP group, compared with the normal group. Rofecoxib decreased retinal angiogenesis by inhibiting COX-2 and VEGF expression. The expression levels of VEGF and COX-2 were positively correlated at mRNA and protein levels. COX-2 and VEGF expressions were both involved in the regulation of angiogenesis and had the same cellular localization. Expression of COX-2 correlated positively with VEGF in retinal neovascularization. Rofecoxib attenuated retinal angiogenesis by inhibiting the expression of COX-2 and VEGF mRNA and protein.