Paul Russell, PhDResearcher in Surgical and Radiological SciencesUniversity of California, DavisSchool of Veterinary MedicineHost: Professor Mark Johnson*Start Time: 5:00PM

Title:"The Biomechanics of the Ocular Trabecular Meshwork"Abstract:Glaucoma is a major cause of blindness throughout the world, and despite the devastating consequences of this disease, the exact mechanisms leading to glaucoma remain unknown. The only proven effective therapy against the progression of glaucoma is to lower the intraocular pressure (IOP). However, none of the approved, commercially available drugs specifically target the human trabecular meshwork (HTM) cells that play a central role in the regulation of intraocular pressure under normal and diseased conditions.It has been well established that intrinsic biophysical properties of the cellular microenvironment have as profound an effect on cellular behavior as biochemical signals. Substrate stiffness has been shown to be a key regulator that modulates many fundamental HTM cell properties. Data from our laboratory demonstratedthe glaucomatous HTM is dramatically stiffer than normal HTM. When stiffness is replicated in substrates in vitro, these biophysical cues lead to striking increases in the expression of genes associated with glaucoma that may ultimately influence resistance to outflow.Currently there are no good animal models for glaucoma; however, glucocorticoid steroids can induce ocular hypertension and may offer a means to study how changes in stiffness are related to glaucoma. Using the atomic force microscope, we have shown that steroids stiffen the meshwork in vivo as well as alter cellular mechanics and extracellular matrix morphology and mechanics. Using cell derived matrices from glaucomatous individuals, our laboratory has determined that these matrices will cause normal cells to increase their stiffnessand become more responsive to steroid treatment.Finally, age is a factor associated with the development of glaucoma and senescence of meshwork cells shows the senescing cells have increased stiffness. One of the proteins increased with senescence can profoundly alter cell stiffness and implicates the Wnt signaling pathway in glaucoma.At the end of this talk, my expectation is that you will have an understanding of (1) the aqueous humor outflow pathway in the eye and how it is related to glaucoma, (2) how the atomic force microscope can be used to study the changes in biomechanical properties both in vivo and in vitro and (3) how analyses of the changes in stiffness in the meshwork can lead to signaling processes that might be altered with disease.