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J.M. Barnett, J.A. Fowler, G.W. McCollum, R. Yang, J.S. Penn; Hypoxia–Induced COX–2 Translocation: In vivo and in vitro Studies . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4188.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Cyclooxygenase–2 (COX–2) promotes VEGF induction through at least one of its products – PGE2. In order to better understand the role of COX–2 in retinal VEGF regulation, the spatial and temporal distribution and level of retinal cyclooxygenase–2 was determined in a rat model of ROP. The corresponding levels of PGE2 and other prostaglandins were also measured. Methods: Using the rat model of ROP, we measured retinal prostaglandin levels by gas chromatography–mass spectrometry and COX–2 levels and distribution by western blot analysis and immunohistochemistry. Additionally, primary retinal Müller cells were isolated from 14 day old C57BL/6 and exposed to hypoxia for 24 hours. The cells were then immunolabeled for COX–2 0, 6, 12, and 24 hours after removal to room air. Results: Immunolabeling of sectioned retinas revealed a nuclear association of COX–2 in both one day post–oxygen–injured animals and room air controls. A translocation of COX–2 from the nucleus to the cytosol was observed at 3 and 6 days post–exposure, as compared to age matched room air controls. Western blots for these samples revealed no change in retinal COX–2 protein levels between any of the time points or between treatment groups. Müller cells exposed to hypoxia showed similar intracellular translocation of COX–2 when compared to normoxic control cells. The gas chromatography–mass spectrometry measurements revealed 3– to 7–fold increases in the levels of various prostaglandins in oxygen injured retinas compared to room air controls. Conclusions: Intracellular translocation of COX–2 without upregulation of protein expression was associated with increased prostaglandin concentrations, associated with in upregulation of VEGF. Continued research into the induction VEGF by COX–2 derived prostaglandins may identify additional and novel therapeutic targets.
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