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Rofecoxib inhibits retinal neovascularization via down regulation of cyclooxygenase‐2 and vascular endothelial growth factor expression
Author(s) -
Liu Ningning,
Sun Yizhou,
Zhao Ning,
Chen Lei
Publication year - 2015
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.12473
Subject(s) - angiogenesis , medicine , retinopathy of prematurity , retinal , vascular endothelial growth factor , neovascularization , western blot , rofecoxib , vascular endothelial growth factor a , cyclooxygenase , immunohistochemistry , endocrinology , andrology , immunology , ophthalmology , vegf receptors , biology , biochemistry , enzyme , pregnancy , genetics , gestational age , gene
Background To explore the anti‐angiogenesis mechanism of R ofecoxib and determine whether R ofecoxib can be a therapeutic agent for the prevention of retinal neovascularization using a model of retinopathy of prematurity ( ROP ). Methods ROP was induced by exposing mice to 75% oxygen from postnatal day 7 ( P 7 ) to P 12 , then to room air from P 12 to P 17 . 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 P 17 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. Results Mice in the R ofecoxib‐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. R ofecoxib 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. Conclusions 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.