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National Glaucoma Research - Current Award

Dr. Mark Johnson

Mark Johnson, Ph.D.

Northwestern University
Evanston, IL

Title: Biomechanical Characterization Of SC Cells
Non-Technical Title: Cell Stiffness In Glaucoma

Acknowledgements: Recipient of the Thomas R. Lee award for National Glaucoma Research
Duration: April 1, 2009 - March 31, 2011
Award Type: Standard
Award Amount: $84,197


Summary:

Are the cells of the inner wall of Schlemm's canal stiffer in glaucomatous eyes than in normal eyes? If so, is this stiffness change responsible for the elevated intraocular pressure characteristic of glaucoma.

Details:


We are investigating the biomechanical characteristics of cells of the aqueous outflow pathway to see if they are different in glaucomatous eyes as compared to normal eyes. If so, in the future, we will explore the molecular and cellular mechanisms underlying this pathology, and potentially be able to develop more effective pressure-lowering treatments or a cure for this debilitating disease.

The specific aims of this project are to:

1. Use atomic force microscopy to determine if cells in the aqueous outflow pathway are stiffer in glaucomatous eyes as compared to normal eyes.

2. Determine the consequence of such a stiffness change on pressure-induced deformations of these cells.

Progress Updates:

Aqueous humor is produced by the ciliary body cells behind the iris (in the posterior chamber) and flows into the front of the eye (into the anterior chamber) and then out of the eye through a specialized pathway. However, in glaucoma, there is a problem, or a “resistance” to the outflow of this aqueous humor through this pathway, causing increased intraocular pressure and eventually leading to damage of the optic nerve. The cells of the inner wall endothelium of Schlemm's Canal (SC) may be involved in the increased aqueous humor outflow resistance characteristic of primary open angle glaucoma. SC is a circular structure in the eye that collects aqueous humor from the anterior chamber and delivers it into the bloodstream. The mechanical properties of SC cells determine the magnitude of the transcellular pressure gradient they can support, and may indirectly regulate the outflow resistance of this cell layer.

We have used atomic force microscopy (a cell measurement and imaging machine) to measure the mechanical properties of SC cells taken from the eyes of normal donors in order to compare them with SC cells from individuals with glaucoma. We measured cell stiffness and, by taking into consideration the location of the measurement, we determined the relative contribution of the cell membrane and cytoskeleton to cell stiffness. We also use these measurements in modeling studies to characterize how SC cells deform under increasing pressure.