Pseudoexfoliation syndrome is a common age-related disease of worldwide significance and is the most commonly identified specific cause of open-angle glaucoma. The disease initiating mechanisms of pseudoexfoliation syndrome are almost completely unknown. Currently, all therapeutic strategies for pseudoexfoliative glaucoma aim to lower IOP and there are no specific therapies aimed at treating pseudoexfoliation syndrome itself. With increased knowledge of the initiating mechanisms, it should be possible to devise improved therapeutic strategies that specifically target pseudoexfoliation syndrome itself, promoting earlier interventions and improved medical outcomes. Our long-term goal is to contribute to the development of improved human glaucoma therapies by utilizing synergistic genetic approaches with mice and humans. Here, we take advantage of a phenotype-driven screening approach among mouse coat color variants that has identified a new mouse model of eye disease that strongly resembles aspects of pseudoexfoliation syndrome. Our objective in this proposal is to capitalize on this resource by initiating mechanistic studies and completing a phenotypic characterization of the strain. Using genetic approaches in mice, we are testing the hypothesis that susceptibility of the eye toward PEX syndrome is mediated via a mechanism influencing cellular morphology and oxidative stress associated with melanogenesis. Suspecting that the same mechanism likely underlies human PEX syndrome, we are simultaneously conducting human genetic association studies. Completion of these studies will not only identify PEX syndrome-related genetic pathways, but will also develop an animal model needed for development and testing of future therapeutic strategies. In the long-term, these experiments will contribute to a better understanding of glaucoma, and ultimately, to improved human therapies. Pseudoexfoliation syndrome is a common age-related disease of worldwide significance and is the most commonly identified specific cause of open-angle glaucoma. Here, we take advantage of a newly identified mouse model that strongly resembles aspects of pseudoexfoliation syndrome. Our objective in this proposal is to test the genetic pathways contributing to phenotypes of this mouse strain and test the significance of these genes among human pseudoexfoliation patients.
| Chirco, Kathleen R; Lewis, Carly J; Scheetz, Todd E et al. (2018) Evaluation of sFLT1 protein levels in human eyes with the FLT1 rs9943922 polymorphism. Ophthalmic Genet 39:68-72 |
| Anderson, Michael G; Meyer, Kacie J; Hedberg-Buenz, Adam et al. (2018) Update on Animal Models of Exfoliation Syndrome. J Glaucoma 27 Suppl 1:S78-S82 |
| Batawi, Hatim; Lollett, Ivonne Valentina; Maliakal, Cima et al. (2018) A Comparative Study of Central Corneal Epithelial, Stromal, and Total Thickness in Males With and Without Primary Open-Angle Glaucoma. Cornea 37:712-719 |
| Dutca, Laura M; Rudd, Danielle; Robles, Victor et al. (2018) Effects of sustained daily latanoprost application on anterior chamber anatomy and physiology in mice. Sci Rep 8:13088 |
| Wang, Chen; Brancusi, Flavia; Valivullah, Zaheer M et al. (2018) A novel iris transillumination grading scale allowing flexible assessment with quantitative image analysis and visual matching. Ophthalmic Genet 39:41-45 |
| Fingert, John H; Miller, Kathy; Hedberg-Buenz, Adam et al. (2017) Transgenic TBK1 mice have features of normal tension glaucoma. Hum Mol Genet 26:124-132 |
| Meyer, Kacie J; Anderson, Michael G (2017) Genetic modifiers as relevant biological variables of eye disorders. Hum Mol Genet 26:R58-R67 |
| Lewis, Carly J; Hedberg-Buenz, Adam; DeLuca, Adam P et al. (2017) Primary congenital and developmental glaucomas. Hum Mol Genet 26:R28-R36 |
| Zarei, Kasra; Scheetz, Todd E; Christopher, Mark et al. (2016) Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ. Sci Rep 6:26559 |
| Hedberg-Buenz, Adam; Christopher, Mark A; Lewis, Carly J et al. (2016) Quantitative measurement of retinal ganglion cell populations via histology-based random forest classification. Exp Eye Res 146:370-85 |
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