Development of an in vitro model of glaucoma

Optic nerve degeneration in glaucoma is typically, but not universally, accompanied by elevated intraocular pressure (IOP). It has been hypothesized that the mechanical forces caused by elevated IOP lead to the glaucomatous damage, however, the mechanism by which elevated IOP leads to vision loss is unknown. We have developed an in vitro model of cell injury which uses fluid shear stress to apply a controlled strain to cultured cells. We used a strain energy method to estimate the stress and strain expected in the optic disc during elevated IOP. We found that fluid shear stress and strain on a differentiated neuroblastoma cell line, retinal neurons, and a glioma cell line led to cell death, probably via apoptosis. In neuron-like cells, the mechanism involved increased nitric oxide production and calcium release from stores. Similar results were observed in retinal neurons. The glioma cell line responded to shear stress via a loss of cell viability and a 6 fold increase in glutamate concentration in the culture medium. We believe the model developed will be useful in examining the mechanism of glaucoma and screening new treatments for the disease