Glaucoma is a leading cause of irreversible blindness and visual disability that has a major impact on the quality of life and productivity of millions of Americans. With no new pharmaceutical classes for treating glaucoma introduced into clinical practice since the 1990s, there remains a continuing need for improved regimes that treat glaucoma more effectively. Our long-term goal is to contribute to the development of these improved therapies by utilizing synergistic genetic approaches with mice and humans. Here, we focus on a sub-type of glaucoma, pigmentary glaucoma, and its major risk factor, pigment dispersion syndrome. Pigment dispersion is an alarmingly common condition characterized by aberrant release and collection of pigment throughout the anterior chamber of the eye. In most people, pigment dispersion causes no significant problems. However, in others, pigment dispersion leads to elevated intraocular pressure and pigmentary glaucoma. The factors initiating pigment dispersion and determining these very different potential outcomes are largely unknown. Our central hypothesis is that dispersed pigment elicits active, modifiable, physiological responses by the trabecular meshwork that are shaped by genetics and that dictate whether or not the insult progresses to secondary glaucoma. Using human genetics, we are studying families affected by pigment dispersion to identify genetic factors causing initiation of pigment dispersion. Using approaches with mice, we have developed an inducible mouse model for studying physiological responses to pigment dispersion and identified genetic suppressors of pigmentary glaucoma for studying potential treatments. Our objective in this proposal is to utilize and build on these resources to study molecular events contributing to pigment dispersion and its conversion to pigmentary glaucoma. To accomplish this, we propose: (SA1) to identify genes linked with pigmentary glaucoma using human genetics, (SA2) to define predictors of ocular responses to pigment dispersion using inducible mouse models, and (SA3) to identify suppressors of pigmentary glaucoma using mouse models.
Glaucoma is a leading cause of irreversible blindness. Our research focuses on studies of pigmentary glaucoma, a common sub-type of glaucoma. The results will provide insight into the molecular pathways that lead to disease and may offer a pathway toward deployment of new glaucoma therapeutics.
|Hedberg-Buenz, Adam; Christopher, Mark A; Lewis, Carly J et al. (2016) RetFM-J, an ImageJ-based module for automated counting andÂ quantifying features of nuclei in retinal whole-mounts. Exp Eye Res 146:386-92|
|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|
|Zarei, Kasra; Scheetz, Todd E; Christopher, Mark et al. (2016) Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ. Sci Rep 6:26559|
|Koehn, Demelza; Meyer, Kacie J; Syed, Nasreen A et al. (2015) Ketamine/Xylazine-Induced Corneal Damage in Mice. PLoS One 10:e0132804|
|Gramlich, Oliver W; Ding, Qiong J; Zhu, Wei et al. (2015) Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients. Acta Neuropathol Commun 3:56|
|Koehn, Demelza R; Meyer, Kacie J; Anderson, Michael G (2015) Genetic Evidence for Differential Regulation of Corneal Epithelial and Stromal Thickness. Invest Ophthalmol Vis Sci 56:5599-607|
|Fernandes, Kimberly A; Harder, Jeffrey M; Williams, Pete A et al. (2015) Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities. Exp Eye Res 141:42-56|
|Dutca, Laura M; Stasheff, Steven F; Hedberg-Buenz, Adam et al. (2014) Early detection of subclinical visual damage after blast-mediated TBI enables prevention of chronic visual deficit by treatment with P7C3-S243. Invest Ophthalmol Vis Sci 55:8330-41|
|Gorniak, Thomas; Haraszti, Tamas; Garamus, Vasyl M et al. (2014) Nano-scale morphology of melanosomes revealed by small-angle X-ray scattering. PLoS One 9:e90884|
|John, Simon W M; Harder, Jeffrey M; Fingert, John H et al. (2014) Animal models of exfoliation syndrome, now and future. J Glaucoma 23:S68-72|
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