Activated microglia in the human glaucomatous optic nerve head

fo investigate the distribution and potential participation of microglia, t he resident defense cells of the central nervous system, in the optic nerve head (ONH) in glaucoma, histological paraffin sections of optic nerves fro m normal and glaucoma patients with mild to advanced nerve damage were stud ied using double labeling immunohistofluorescence. A monoclonal antibody fo r HLA-DR, indicating activated microglia, was colocalized with antibodies f or functional proteins. In normal ONHs, microglia do not contain TGF-beta2, COX-2, or TNF-alpha and are not positive for PCNA; however, in glaucomatou s ONHs, microglia contain abundant TGF-beta2, TNF-alpha, and PCNA. In glauc omatous eyes, a few microglia are usually positive for COX-2. In normal ONH s, there are rarely microglia containing TGF-beta1, NOS-2, TSP, TIMP-2, and CD68, but, in glaucomatous tissue, a few microglia are positive from the p relaminar to the postlaminar regions. MMP-1, MMP-2, MMP-3, and MMP-14 are c onstitutively present in the perivascular microglia in normal ONHs and appe ar to be more abundant in glaucomatous tissue. COX-1, TNF-R1,TIMP-1, and c- fms are constitutively present in normal tissues and appear to be increased in microglia in the glaucomatous ONHs. HSP27 is not present in microglia. In glaucomatous ONHs, microglia become activated and phagocytic and produce cytokines, mediators, and enzymes that can alter the extracellular matrix. Our findings suggest that activated microglia may participate in stabilizi ng the tissue early in the disease process, but, as the severity of the gla ucomatous damage increases, the activities of microglia may have detrimenta l consequences for the pathological course of glaucomatous optic neuropathy . (C) 2001 Wiley-Liss, Inc.