Areas of Research Focus
Glaucoma is a multifactorial complex disease that involves pathologies in the anterior chamber affecting the outflow of aqueous humor, and the neurodegeneration of the optic nerve and retinal ganglion cell somas in the retina. In addition to the traditional “inner retinal” disease component (retinal ganglion cell loss), there is increasing evidence that other retinal cell types are affected as part of the pathology. The UW GRG has vital and active research programs in virtually all areas of glaucoma research.
- Cell and Molecular Biology – ongoing studies include the analysis of cellular interactions and the role of the cytoskeleton in cells of the trabecular meshwork, and the molecular pathology of retinal ganglion cell loss.
Genetics – ongoing studies evaluate and fine map the genetic contributions to ocular hypertension and optic disc parameters in large-scale epidemiologic studies, linkage analysis to identify genes involved in the development of congenital glaucoma, and reverse genetic approaches in mice to identify glaucoma susceptibility alleles. In addition, a novel cat model of inherited congenital glaucoma is being developed and characterized.
- Physiology – ongoing studies to monitor the changes in retinal function are being actively pursued, including the use of multifocal ERG, pattern ERG, and visual evoked potential measurements on both human glaucoma and non-human experimental glaucoma models. Anterior segment physiology studies investigate the effects of pharmacotherapy, surgical manipulations and gene therapy on IOP, aqueous humor formation and drainage.
- Non-invasive imaging – the GRG is a leader in the use of non-invasive technologies (including OCT and GDx) to monitor structural retinal and optic nerve changes longitudinally in both humans with disease and animals models of experimental glaucoma.
- Pharmacology and novel Therapeutics – both the development of small molecules and gene therapeutic approaches to enhance outflow and prevent ganglion cell loss are active programs in the GRG.
Surgical management – programs include the development of novel anti-scarring treatments for the use in trabeculectomy surgery, and the evaluation of surgical IOP-lowering strategies in animal models of experimental glaucoma.
A major strength of the GRG is the development and use of animal models for research. These models include experimental glaucoma in non-human primates and rodents, the DBA/2J mouse model of inherited glaucoma, and inherited congenital glaucoma in cats. In addition, members of the GRG utilize a variety of in vitro technologies, including anterior segment organ cultures, TM cell, retinal explants for regeneration, primary cultures of neonatal retinal ganglion cells, and the neuronal precursor 661W cell line.
Several members of the GRG facilitate operations of the DOVS Vision CORE modules, including the development of non-replicating viral vectors for gene therapy, quantitative molecular technologies (qPCR and Luciferase based gene expression studies, and genome wide SNP mapping), fluorescent microscopy, live cell imaging using spinning disc confocal microscopy, anterior and posterior segment physiology, and imaging in vivo.
Plans/desires for new membership (and mentoring plan): New membership is always welcome. Future plans are to expand the GRG to include active membership and become a vital resource for groups outside the UW sphere.
Areas of Expected/Desired Growth
Discipline and Space Requirements
Development of a Glaucoma Research Center – a long-range goal is to consolidate glaucoma research into a group of laboratories in close proximity to each other. Currently, glaucoma research in DOVS is equally split between the CSC and MSC. The acquisition of development funds would enable separated laboratories to consolidate programs and resources in one of the WIMR towers. This presents the opportunity for a named center on campus.
Addition and development of a zebrafish model of optic nerve disease to study the mechanisms of ganglion cell protection and optic nerve regeneration inherent in the zebrafish. Foster the development of an independent research program of Dr. Jon Skarie, who specializes in zebrafish biology.
Expansion of the vision CORE facilities to include an integrated genomics facility. A genomics facility would facilitate the modern genetics approach to the study of glaucoma and we expect that it would require planning for one or two new hires. A potential mechanism for this would be to bring in one or two glaucoma researchers under the umbrella of the epigenetics/genomics initiative underway at the Wisconsin Institute of Discovery.