In primary open-angle glaucoma, elevated intraocular pressure is associated with distortion and reorganization of the connective tissue plates of the lamina cribrosa. We have previously postulated that the resident cells of the lamina cribrosa may respond to elevated intraocular pressure by altering the biosynthesis or degradation of extracellular matrix. To determine the response of lamina cribrosa cells to increased pressure, we have compared cultures of human lamina cribrosa cells, from five individuals, maintained under control and pressurized conditions in vitro. Cells from third to fifth passage cultures of human lamina cribrosa subjected to elevated hydrostatic pressure (50 mm Hg) for 7 days changed shape from flat and polygonal to elongated, synthesized and secreted increased amounts of collagen type I as shown by immunofluorescent localization, and exhibited increased mRNA levels of collagen type I (199 +/- 36% of control) (mean +/- S.D.), as determined by slot-blot hybridization. In contrast, beta-actin mRNA levels were unchanged, indicating that the effects of elevated pressure are probably relatively selective. Our data indicate that elevated pressure increases the synthesis of collagen Type I by human lamina cribrosa cells in vitro. In vivo, lamina cribrosa cells may react to changes in their environment by modulating, specifically, changes in the mRNA levels, production, and secretion of extracellular matrix macromolecules. The relationship of these changes in extracellular matrix to those observed in glaucoma remains to be determined.