Glaucoma is a blinding disease affecting millions of people around the world;primary open angle glaucoma (POAG) is the most common form (70-90%). Over 14 POAG loci have been mapped but only 4 of these genes have been identified. Our lab has mapped three of the POAG loci and just recently identified the causative gene for GLC1F. The long-term goal of this proposal is to elucidate how POAG genes cause glaucoma. Our working hypothesis is that each glaucoma locus represents a specific disease entity within the POAG hierarchy and thus, will present with distinct findings, e.g. high intraocular pressure, fast onset of disease or characteristic defects in the optic nerve. In this proposal we seek to identify the genes for the two remaining loci, GLC1C and GLC1G.
Our specific aims are:
7 Specific Aim 1. Identify the GLC1G gene and determine the incidence of mutations in POAG populations 7 Specific Aim 2. Identify the GLC1C gene and determine the incidence of mutations in POAG populations.
7 Specific Aim 3. Characterize expression of the GLC1C and GLC1G gene in the anterior segment of the eye, trabecular meshwork cells, and optic nerve of normal and glaucomatous eyes. Completion of these specific aims will increase our knowledge of the genes that cause glaucoma. Potentially either the GLC1C or GLC1G gene may impact a larger proportion of the POAG population than previously identified genes. However, even if they affect only 4-8% of the glaucoma population, identification of these genes will still be of importance because of the pathways that these genes impact. Research into these pathways will lead to a better understanding of what causes glaucoma and ultimately to better treatments based upon this knowledge.
Identification of new glaucoma genes will give insight into what pathways are impacted in glaucoma. This will lead to development of new treatments based upon knowledge of how these pathways function. Better treatments and earlier diagnosis will be based upon a clearer understanding of the clinical phenotypes represented by each locus.
|Keller, Kate E; Yang, Yong-Feng; Sun, Ying Ying et al. (2014) Interleukin-20 receptor expression in the trabecular meshwork and its implication in glaucoma. J Ocul Pharmacol Ther 30:267-76|
|Keller, Kate E; Yang, Yong-Feng; Sun, Ying Ying et al. (2013) Ankyrin repeat and suppressor of cytokine signaling box containing protein-10 is associated with ubiquitin-mediated degradation pathways in trabecular meshwork cells. Mol Vis 19:1639-55|
|Sengle, Gerhard; Tsutsui, Ko; Keene, Douglas R et al. (2012) Microenvironmental regulation by fibrillin-1. PLoS Genet 8:e1002425|
|Pasutto, Francesca; Keller, Kate E; Weisschuh, Nicole et al. (2012) Variants in ASB10 are associated with open-angle glaucoma. Hum Mol Genet 21:1336-49|
|Charlesworth, Jac; Kramer, Patricia L; Dyer, Tom et al. (2010) The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness. Invest Ophthalmol Vis Sci 51:3509-14|
|Wirtz, Mary K; Samples, John R; Toumanidou, Victoria et al. (2010) Association of POAG risk factors and the Thr377Met MYOC mutation in an isolated Greek population. Invest Ophthalmol Vis Sci 51:3055-60|
|Wirtz, Mary K; Konstas, Anastasios G P; Samples, John R et al. (2008) Myocilin variations and familial glaucoma in Taxiarchis, a small Greek village. Mol Vis 14:774-81|
|Hewitt, Alex W; Samples, John R; Allingham, R Rand et al. (2007) Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgrounds. Mol Vis 13:487-92|
|Wirtz, Mary K; Samples, John R; Choi, Dongseok et al. (2007) Clinical features associated with an Asp380His Myocilin mutation in a US family with primary open-angle glaucoma. Am J Ophthalmol 144:75-80|
|Rozsa, Frank W; Scott, Kathleen M; Pawar, Hemant et al. (2007) Differential expression profile prioritization of positional candidate glaucoma genes: the GLC1C locus. Arch Ophthalmol 125:117-27|
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