Text Size Normal Text Sizing Button Medium Text Sizing Button Large Text Sizing Button Text Contrast Normal Contrast Button Reverse Contrast Button Switch to Spanish Language Press Room Contact Us Sitemap Sign In Register
Link to Homepage About BrightFocus
BrightFocus
Donate Now Get Involved  
Alzheimer's Disease Research Macular Degeneration Research National Glaucoma Research


Sign up for Email Notifications
If you would like to be notified when funding or meeting opportunities are announced please click on the link below.

Sign up for new announcements.

Please add ResearchGrants@BrightFocus.org to your institution’s white list to insure that the notification is not blocked by your organization’s SPAM filters.

This email list is not sold or distributed, and serves only as an annual reminder of the availability of research support through the BrightFocus Foundation (www.brightfocus.org). Please follow instructions on the notification emails for removal requests.

 
 
BrightFocus Research Grants Funding
Grant Funding for Alzheimer's Research
Grant Funding for Macular Degeneration Research
Grant Funding for Glaucoma Research
 

 

National Glaucoma Research
Current Award

Dr. Michael H. Elliott

Michael H. Elliott, Ph.D.

University of Oklahoma Health Sciences Center
Oklahoma City, OK

Title: Caveolins as Novel Mechanosensors in Aqueous Outflow
Non-Technical Title: Novel Mechanism of Control of Aqueous Fluid Drainage

Acknowledgements: Recipient of the Thomas R. Lee Award for National Glaucoma Research
Duration: July 1, 2013 - June 30, 2015
Award Type: Standard
Award Amount: $100,000

Summary:

Elevated eye pressure is a major risk factor for glaucoma and this pressure is regulated by controlling the drainage of fluid from the eye. There are currently no glaucoma medications that target the major pathway of fluid drainage in the eye, yet this pathway is the source of the primary cause and progression in open-angle glaucoma. Dr. Elliott’s project is designed to test a novel mechanism by which the eye regulates fluid drainage and how this mechanism might be dysfunction in glaucoma.

Details:

The goal of this project is to test a novel concept of how eye pressure is controlled in normal and pathological conditions. Glaucoma is a heterogeneous group of diseases that represents the second leading cause of blindness worldwide, with primary open-angle glaucoma being the most prevalent form. Elevated pressure in the eye is the major risk factor in developing primary open angle glaucoma. Eye pressure is controlled by the rate at which fluid, called aqueous humor, is produced and the speed at which this fluid drains from the eye. In the normal eye, this drainage process is tightly regulated in order to maintain optimal pressure. In many forms of glaucoma, this drainage system does not work effectively leading to elevations in eye pressure. The mechanisms that tightly regulate the speed of fluid drainage are unknown, but are likely to involve a mechanical pressure sensor, similar to a thermostat, that causes drainage to increase if pressure increases and resists drainage if pressure is too low. The nature and cellular location of this "molecular thermostat" is unknown.

Recently, human gene association studies have linked the CAV1 gene with increased risk of developing primary open-angle glaucoma. This gene, which Dr. Elliott's laboratory has been studying for several years, is known to form specialized domains in cell membranes called "caveolae." There is emerging evidence that these domains may be cellular sensors for mechanical changes in cells, such as those that might result from increases in eye pressure. Dr. Elliott's team thinks that caveolae may be the sensors that regulate fluid drainage and that mutations in the CAV1 gene may render this sensor defective. Dr. Elliott has been given the BrightFocus Foundation Thomas R. Lee Award for National Glaucoma Research to test this groundbreaking idea, and also will search for the cellular location of this mechanical sensor.

The first aim of this project will address whether the membrane domains called caveolae respond to experimentally-increased eye pressure, and whether molecules associated with these membrane domains change in their location within the cells responsible for fluid drainage.
The second aim will examine the cellular location of the caveolae-dependent pressure sensor. A fundamental question in the glaucoma research field is what cell type is responsible for generating resistance to fluid drainage. Dr. Elliott's team has the unique ability to manipulate the gene necessary for caveolae formation in a cell-specific context allowing them to ask whether, for example, caveolae in the drainage vessel, called Schlemm's canal, is the site of pressure-dependent resistance to fluid drainage.

This proposed study has important translational implications as it will test a novel concept in fluid drainage outflow regulation that will provide the rationale for new therapeutic strategies for eye pressure regulation. We are indebted to the BrightFocus Foundation for its support and are honored to receive the Thomas R. Lee Award for National Glaucoma Research to help us develop this exciting project.

Publications:

Gu X, Fliesler SJ, Zhao YY, Stallcup WB, Cohen AW, Elliott MH. Loss of
caveolin-1 causes blood-retinal barrier breakdown, venous enlargement, and mural
cell alteration. Am J Pathol. 2014 Feb;184(2):541-55. doi: 10.1016/j.ajpath.2013.10.022. Epub 2013 Dec 8. PubMed Icon Google Scholar Icon

Investigator Biography:

Dr. Elliott is an Assistant Professor of Ophthalmology in the Dean McGee Eye Institute of the University of Oklahoma Health Sciences Center. Dr. Elliott received his Ph.D. from the University of Kansas and went on to complete a postdoctoral fellowship at the University of Oklahoma Health Sciences Center. Dr. Elliott’s research focuses on the role(s) that membrane domains regulate cell function in physiological and pathological ocular diseases including retinal degenerations, diabetic retinopathy, and glaucoma. The BrightFocus-supported project will test the hypothesis that membrane domains, called caveolae, provide mechanosensitive platforms to couple changes in eye pressure to fluid drainage. In addition to this BrightFocus award, Dr. Elliott has recently received a prestigiousYoung Investigator award from the Alcon Research Institute. Other projects in his laboratory are supported by the National Eye Institute, the American Diabetes Association, and the Oklahoma Center for Adult Stem Cell Research.