National Glaucoma Research
Darryl R. Overby, Ph.D.
Imperial College London
Title: Are Mice Good Models of IOP Regulation in Human Eyes?
Non-Technical Title: Are Mice Good Animal Models to Study How Pressure is Regulated in Human Eyes?
Acknowledgements: Recipient of the Thomas R. Lee award for National Glaucoma Research.
Duration: July 1, 2011 - June 30, 2013
Award Type: Standard
Award Amount: $100,000
The success of glaucoma therapies depends on how well they lower pressure in the eye, and these therapies are often developed with the help of animal models such as mice. However, it is not entirely clear whether the mechanisms controlling pressure in mouse eyes are representative of the pressure controlling mechanisms in human eyes. This project investigates whether mice are good animal models in which to develop better therapies to more successfully lower pressure in human eyes.
The success of glaucoma therapies depends on how well they lower pressure in the eye, and successful therapies are often developed with the help of animal models such as mice. However, a drug found to lower pressure in mice is useless in humans if the machinery controlling eye pressure is different between the two species. Recent studies suggest that pressure regulation in some strains of mice relies more heavily on a secondary or "uveoscleral" pathway for fluid drainage from the eye, while human pressure regulation depends more on the primary or "trabecular" drainage pathway. Not all strains of mice, however, appear to exhibit the same preference for drainage routes, suggesting that some strains may better represent the trabecular pressure regulation as occurs in humans. In this project, Dr. Darryl Overby and colleagues will examine genetically distinct strains of mice chosen based upon their apparent differences in drainage behaviour, with the goal to identify which of these strains best mimics the machinery that controls pressure in human eyes. This is an important first step towards establishing a reliable mouse model that can be used to develop better therapies that more successfully lower pressure and preserve vision in glaucoma patients.
Boussommier-Calleja A, Bertrand J, Woodward DF, Ethier CR, Stamer WD, and Overby DR. Pharmacologic manipulation of conventional outflow facility in ex vivo mouse eyes. Investigative Ophthalmology and Visual Science, 54:5838-5845, 2012.
Francis A, Kagemann L, Wollstein G, Ishikawa H, Folz S, Overby DR, Sigal IA, Wang B, Schuman JS. Morphometric analysis of aqueous humor outflow structures with spectral domain optical coherence tomography. Investigative Ophthalmology and Visual Science, 2012. In Press.
Dr. Overby’s team’s progress over the past year has established that mouse eyes share similar pressure-regulating pharmacological and physiological mechanisms as previously reported in human eyes. These studies will help to establish whether mice are good animal models in which to screen and develop improved therapies to more successfully lower pressure in human eyes, ultimately to better preserve vision in glaucoma patients.
Dr. Overby received his PhD from MIT in 2002 in Mechanical Engineering, with a research focus in the areas of biomechanics and biological transport phenomena applied to glaucoma. He then did a 3 year post-doctoral fellowship in cellular biomechanics and vascular biology at Harvard Medical School and Children's Hospital in Boston. Between 2004 and 2008, he served as Assistant Professor in the Department of Biomedical Engineering at Tulane University, holding the Ken and Ruth Arnold Early Career Professorship of Science and Engineering. Since 2008, he has served in the Department of Bioengineering as a Lecturer at Imperial College London. Dr. Overby's research is supported by the National Institutes of Health, National Eye Institute, the BrightFocus Foundation, and Allergan, Inc.