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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (DPVS)
Program Officer
Chin, Hemin R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code
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

Showing the most recent 10 out of 35 publications