Expression of cyclooxygenase-1 and-2 in normal and glaucomatous human eyes

Citation
C. Maihofner et al., Expression of cyclooxygenase-1 and-2 in normal and glaucomatous human eyes, INV OPHTH V, 42(11), 2001, pp. 2616-2624
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN journal
0146-0404 → ACNP
Volume
42
Issue
11
Year of publication
2001
Pages
2616 - 2624
Database
ISI
SICI code
0146-0404(200110)42:11<2616:EOCAIN>2.0.ZU;2-T
Abstract
PURPOSE. Primary open-angle glaucoma (POAG) is the predominant form of chro nic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a cha nge in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. METHODS. Expression of COX-I and -2 was assessed by confocal laser microsco py, immunohistochemistry, Western blot analysis, and real-time RT-PCR in hu man eyes with different forms of glaucoma (primary open-angle, angle-closur e, congenital juvenile, and steroid-induced), as well as in age-matched con trol eyes. Additionally, PGE(2) was measured in aqueous humor by means of a n enzyme-linked immunoassay as a product of COX activity. RESULTS. In normal eyes, ocular COX-1 and -2 expression were largely confin ed to the nonpigmented secretory epithelium of the ciliary body. By immunoh istochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end -stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistr y, in the ciliary bodies of eyes in five patients with diagnosis of early P OAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2- expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma a nd was reduced in patients receiving topical steroid treatment. Eyes of pat ients with either congenital juvenile or angle-closure glaucoma showed COX- 2 expression indistinguishable from control eyes. Aqueous humor of eyes wit h POAG contained significantly less PGE(2) than control eyes. CONCLUSIONS. Both cyclooxygenase isoforms are constitutively expressed in t he normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurr ence of POAG and steroid-induced glaucoma.