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Timothy P. Fox, Lars Bellner, Katherine Gotlinger, Michael W. Dunn, Gerald W. Zaidman, Michal L. Schwartzman; Genomic and Lipidomic Analyses of Pterygium Pathogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3368.
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Pterygium is an ocular surface disease of humans attributed to chronic ultraviolet-B exposure. It involves invasive centripetal growth with associated inflammation and neovascularization. Cyclooxygenases (COX), lipoxygenases (LOX) and cytochrome P450 monooxygenases (CYP) derived eicosanoids have been implicated in ocular surface inflammation and neovascularization. These eicosanoids are subjected to regulation by enzymes such as heme oxygenases (HO), NADPH oxidases (NOX) and ferritin. We measured the expression of these genes and their products in pterygium.
Quantitative PCR and LC-MS/MS-based lipidomics were performed on pterygium from patients undergoing surgical removal of pterygium. Control tissues consisted of conjunctiva, sclera, and limbus from donor corneal tissues. In addition, LC-MS/MS-based lipidomics was also performed on tears collected from patients prior to surgery.
mRNA-expression of the HO-2, the constitutive HO isoform, was upregulated by 40% in pterygium as compared to control tissue, while the mRNA levels of the inducible form, HO-1, did not differ. mRNA-expression of COX-1, the constitutive COX, was 2-fold higher, whereas the inducible form, COX-2, was 3-fold lower in pterygium compared to normal conjunctiva. The expression of CYP4B1 mRNA showed a 10-fold increase in pterygium compared to control. Lipidomics analysis of tissues indicated a doubling in PGE2 and TxB2 levels in pterygium as compared to control. Among lipoxygenase-derived metabolites, the anti-inflammatory 15-HETE levels were significantly reduced in pterygium (79.3±48.11 pg/mg protein) as compared to control (586.2±213.5 pg/mg protein), whereas pro-inflammatory LOX and CYP4B1-derived 12-HETE levels were 10-fold higher in pterygium (2768±832.3 pg/mg protein) compared to control (231.4±87.35 pg/mg protein). PGE2 and the HETEs were also present in tears from patients with pterygium. Ferritin light chain mRNA expression was 3-fold lower in pterygium as compared to control while levels of NOX-2, NOX-4 and VEGF-R2 showed no significant differences between pterygium and control.
We believe that the increased expression of COX-1 and CYP4B1 as well as the increase in PGE2 and 12-HETE contribute to the pathogenesis of pterygium. Moreover, the lower expression levels of ferritin in pterygium may contribute to the development of the iron-containing Stocker’s line.
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