IL-1/NF-kB Pathway in Glaucomatous Trabecular Meshwork

Project Summary

In glaucoma, retinal cell death and optic nerve damage lead to visual loss. These problems are typically caused by increased intraocular pressure (IOP), due to reduced drainage of fluid through the trabecular meshwork (TM), a network of drainage canals that normally keep excess fluid from building up. Dr. Olson is working to expand on an important finding from other Tufts University researchers who demonstrated the expression of a gene for a cell surface protein, ELAM-1, in the TM of glaucomatous eyes but not in non-glaucomatous eyes. ELAM-1 expression was identified as a first diagnostic marker of glaucomatous TM. In addition, they showed that the IL-1/NF-kB signaling pathway was responsible for ELAM expression, implicating this pathway in the cause of the disease. Dr. Olson is exploring whether there are other proteins activated through the IL-1 pathway that could serve as additional diagnostic markers for glaucoma and/or targets for pharmaceutical intervention. She hopes to determine which proteins are expressed in TM cells using 2D gel analysis in response to IL-1, to identify the proteins using mass spectrometry and to confirm the importance of the proteins by examining their presence in TM tissue dissected from normal and glaucomatous cadaver eyes. A reliable diagnostic marker for early TM pathology would enable clinicians to identify individuals who are at risk and provide early treatment.