Cyclooxygenase-1 and Cyclooxygenase-2 in the Human Optic Nerve Head

Abstract

To investigate the hypothesis that eicosanoids act as cellular mediators in the optic nerve head of normals and of patients with glaucoma, we have determined the presence of the two cyclooxygenase (COX) isoforms in human tissue. Histological sections of optic nerve heads were studied 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 immunoperoxidase staining. Specific antibodies for vascular endothelia and microglia were also co-localized. In normal and glaucomatous eyes, COX-1 was localized exclusively to the prelaminar and lamina cribrosa regions 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 associated with the astrocytes of the glial columns and the cribriform plates, but not with the endothelia lining the capillaries. In glaucoma, more astrocytes appeared to be stained with antibody to COX-1 than in normals 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 glaucomatous optic nerves. Positive staining for COX-2 was not associated with microglia. COX-1 is constitutively present in astrocytes that are localized exclusively to the prelaminar and lamina cribrosa regions of the human optic nerve head. Eicosanoids, synthesized by COX-1 in this tissue, may have a homeostatic and a neuroprotective role related to the axons of the retinal ganglion cells. The sparse presence of COX-2 in glaucomatous tissue probably reflects the lack of inflammation associated with glaucomatous optic neuropathy.