National Glaucoma Research
Darryl Overby, Ph.D.
Imperial College London
Title: Role of PLVAP in Regulation of Aqueous Outflow Facility
Non-Technical Title: Can We Increase the Number of Drainage Pores in the Eye to Better Treat Glaucoma?
Ernst R. Tamm, M.D.
University of Regensburg
Duration: July 1, 2013 - June 30, 2015
Award Type: Standard
Award Amount: $100,000
Glaucoma is a blinding eye disease associated with elevated pressure in the eye, and all treatments for glaucoma attempt to reduce eye pressure to prevent further vision loss. Drs. Overby’s and Tamm’s project investigates how eye pressure is regulated, focusing on a single of layer of cells that create a porous barrier to fluid drainage from the eye. In glaucoma, there are too few pores in this cell barrier, such that fluid drainage is partly blocked and pressure builds. By studying the factors controlling pore formation, Drs. Overby and Tamm hope to one day exploit this process to induce pore formation as a way to enhance drainage and more successfully lower IOP in glaucoma.
The research of Drs. Overby and Tamm focuses on the mechanisms of pressure regulation in the eye, with the goal to understand why pressure becomes elevated in glaucoma and what can be done to more successfully lower pressure to preserve vision in glaucoma patients. They focus their research on a single layer of cells that create a porous barrier to fluid drainage from the eye. This barrier— known as Schlemm’s canal endothelium—becomes altered in glaucoma, having fewer pores that they believe impedes fluid drainage and elevates pressure. Furthermore, their research has established that Schlemm’s canal cells cultured from glaucoma eyes have impaired pore-forming ability.
Drs. Overby and Tamm hypothesize that pore formation is a target for glaucoma therapy, such that if they can rescue normal pore formation in Schlemm’s canal cells from glaucoma eyes, they could enhance drainage and more successfully lower pressure. To do this, however, they must first understand the pore forming machinery in Schlemm’s canal cells, and they have taken a hint from other pore-forming cells elsewhere in the eye, kidney and liver. These other cells form pores (albeit pores that are much smaller than those in Schlemm’s canal) through a protein known as plasmalemmal vesicle-associated protein (PLVAP), and they hypothesize that PLVAP is also important for pore formation in Schlemm’s canal cells. Therefore, Drs. Overby and Tamm are investigating how alterations in PLVAP protein expression affects pressure regulation and barrier function in isolated Schlemm’s canal cells and in donated eyes.
Dr. Overby is a Senior Lecturer in Bioengineering at Imperial College London. He has held previous positions at Tulane University, and completed his doctoral studies at Massachusetts Institute of Technology with post-doctoral training in cellular and vascular bioengineering at Harvard Medical School. Dr. Overby’s laboratory investigates how mechanical forces affect cell biology and tissue function in the eye and cardiovascular system. In addition to the BrightFocus award, Dr. Overby’s research is supported by the National Eye Institute, the Engineering and Physical Sciences Research Council (UK), and the Fight for Sight Foundation (UK). Dr. Overby is a recent recipient of the International Research Scholar Award from the Research to Prevent Blindness Foundation.