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.