Role of TIGR/MYOC Protein in Human TM Cells

Glaucoma is one of the leading causes of blindness worldwide. Primary open angle glaucoma, the most common type, affects millions of individuals in the United States alone. Blindness from this disease is thought to result from an increased pressure within the eye that causes damage to the optic nerve and subsequent loss of vision. The pressure is thought to increase because the fluid in the eye has difficulty draining. Recently, several families that have glaucoma were shown to have mutations in a newly discovered gene called TIGR/MYOC. This gene makes a protein that is located in cells in the part of the eye where the fluid drains. Since this is a new gene, very little research has been done to uncover what it does normally in the eye and what a mutation in this gene does to cause glaucoma. The primary objective of this proposal is the figure out what this gene does. We have used computer data banks of information about millions of other genes and compared it to this TIGR/MYOC gene. Results from these computer analyses show that the TIGR/MYOC gene produces a protein that may be part of the cell cytoskeleton. The cytoskeleton is important because it provides structure for the cell (similar to that of the skeleton for the whole body) so that it can function properly. We hypothesize that the TIGR/MYOC gene produces a protein that functions as a cytoskeletal, or cytoskeletal-associated protein in cells of the part of the eye where fluid drains. To test this hypothesis experimentally, we will use a variety of molecular “tools” to locate this TIGR/MYOC protein in these cells. The molecular “tools” fluoresce, like a firefly, and specifically attach to the TIGR/MYOC protein in these cells. We then use a microscope to see where the TIGR/MYOC protein is located inside these cells. In other experiments, we will make in a test tube a part of the glaucoma protein itself and join it to part of another protein that fluoresces. We will then put this half-glaucoma, half-TIGR/MYOC protein into living cells and watch where it goes using a microscope. Together, information from these two experiments will provide information about what the glaucoma protein does in normal people and those people with glaucoma.