Next Generation Glaucoma Drug Development

For the Project, we will screen candidate adeno associated viruses and engineered promoters cloned into lentiviruses obtained from collaborators in human Schlemm’s canal cells in vitro and anterior segments ex vivo for selective tropism to/activity in trabecular meshwork versus Schlemm’s canal. This is only possible with the generous and faithful support of donors.

All treatments for glaucoma seek to lower intraocular pressure (IOP), yet existing approaches are insufficient. We now understand that endothelial cells of the inner wall of Schlemm’s canal (SC) play a key role in homeostatic control mechanisms that maintain IOP within a target range. However, tools for directly assessing SC inner wall endothelial function are lacking, as are molecular approaches for directly targeting and interrogating these cells. In Subpart B of this multi-institutional award, Dr. Stamer will screen and validate candidate viruses to use for selective knockdown of proteins involved with the connection between cells of the SC. This laboratory will also test drugs that interfere with the structure of SC cells, and monitor and report the amount of shear stress on the SC inner wall cells. Throughout these experiments, they will provide SC cells for development of the drug screening platforms used by the other institutions in this collective.