To investigate the hypothesis that eicosanoids act as cellular mediato
rs in the optic nerve head of normals and of patients with glaucoma, w
e have determined the presence of the two cyclooxygenase (COX) isoform
s in human tissue, Histological sections of optic nerve heads were stu
died by immunohistochemistry. Age matched normal donors were compared
with eyes from glaucoma patients with moderate to severe nerve damage.
Polyclonal antibodies to human COX-1 and COX-2 were localized with im
munoperoxidase staining. Specific antibodies for vascular endothelia a
nd microglia were also colocalized. In normal and glaucomatous eyes, C
OX-1 was localized exclusively to the prelaminar and lamina cribrosa r
egions of the optic nerve head. No staining for COX-1 was observed in
the nerve fiber layer or the myelinated optic nerve. COX-1 was associa
ted with the astrocytes of the glial columns and the cribriform plates
, but not with the endothelia lining the capillaries. In glaucoma, mor
e astrocytes appeared to be stained with antibody to COX-1 than in nor
mals and staining was intensely perinuclear. There was no staining for
COX-2 in normal tissue. A few COX-2 positive cells were found in the
prelaminar, lamina cribrosa and postlaminar regions of the glaucomatou
s optic nerves. Positive staining for COX-2 was not associated with mi
croglia. COX-1 is constitutively present in astrocytes that are locali
zed exclusively to the prelaminar and lamina cribrosa regions of the h
uman optic nerve head. Eicosanoids, synthesized by COX-1 in this tissu
e, may have a homeostatic and a neuroprotective role related to the ax
ons of the retinal ganglion cells. The sparse presence of COX-2 in gla
ucomatous tissue probably reflects the lack of inflammation associated
with glaucomatous optic neuropathy. (C) 1997 Academic Press Limited.