title: The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal Neovascularization and Subretinal Fibrosis.
abstract: Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium-choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-β2 in the retinal pigment epithelium-choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-β2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis.
authors.affiliation: Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
authors.forename: Ruoshuang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
authors.forename: Zheli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The first affiliated hospital of China Medical University, Shenyang City, liaoning Province, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
mesh_terms: D000818:Animals; D002829:Choroid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005355:Fibrosis; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008810:Mice, Inbred C57BL; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide