Rick Libby
Where is he now?
Publications
Dr. Libby did his doctoral work with in Dr. William Brunken’s laboratory (Boston College), where he focused on the role of extracellular matrix in retinal development. After completion of his doctorate, he joined Dr. Karen Steel’s group at the Medical Research Council’s Institute for Hearing Research. There he studied the pathogenesis of Usher Syndrome.
The main focus of Dr. Libby’s research in the John laboratory was to identify the key molecules and pathways that are activated in response to elevated intraocular pressure and lead to vision loss. Vision loss in glaucoma is caused by death of the retinal ganglion cells (RGC; These are the cells that connect the retina to the brain via the optic nerve). Furthermore, he was interested in identifying susceptibility factors underlying glaucomatous neurodegeneration.
The majority of work that Dr. Libby performed in the John Laboratory focused on the DBA/2J mouse glaucoma model. The DBA/2J mouse glaucoma model mimics many human glaucomas in that it is age-related and the pressure elevation is spontaneous and variable. There is now extensive knowledge of the disease profile of DBA/2J mice and have been successfully exploiting this model to gain fundamental insight into glaucomatous neurodegeneration
Using DBA/2J mice deficient in the pro-apoptotic molecule BAX (a molecule that when active, triggers a cell to kill itself), he found that Bax deficiency completely protected retinal ganglion cells (RGCs; the cell bodies or soma) from apoptosis. BAX was the first molecule shown to be necessary for glaucomatous RGC death. However, BAX was not found to be required for RGC axon degeneration. (In addition to a cell body, RGCs have a long process known as an axon that connects them to the brain.) This is important because it is the first data indicating that there are distinct somal and axonal degeneration pathways in glaucoma. Furthermore, since axons degenerated even though the soma did not, these results indicate that somal death is not a prerequisite for axon degeneration in glaucoma.
While Bax deficiency did not protect RGC axons from degeneration, it did delay axon degeneration, implicating BAX as a potential glaucoma susceptibility gene.
These data suggest that a patient’s susceptibility to glaucomatous vision loss could be directly linked to Bax expression levels and that manipulating the BAX pathway could be a powerful mechanism for slowing or preventing vision loss in glaucoma. In collaboration with Dr. Robert Nickells (University of Wisconsin) group, we were also able to use the genetic resource of DBA/2J mice deficient in Bax to evaluate two prominent glaucoma hypotheses. Genetically controlled experiments were performed where RGC cells were insulted by either mechanical axon injury or by an excitotoxin. The findings from these induced cell death models were compared to the findings obtained in the actual DBA/2J glaucoma. As in the actual glaucoma, Bax deficiency protected somas after optic nerve crush, but it did not protect RGC somas from excitotoxic injury. Together, these results support optic nerve injury as a primary cause of RGC death in glaucoma but do not support an excitotoxic mechanism.
During his time in the John Lab, Dr. Libby also participated in other projects ranging from studies designed to identify susceptibility factors for developing glaucoma (blood pressure; problems with eye development) to studies focused on developing neuroprotective therapies (radiation with bone marrow transfer).
Dr. Libby started his own research program at the University of Rochester Medical Center in 2006. He is Assistant Professor in the Department of Ophthalmology where he is continuing to study the molecular pathways of glaucomatous neurodegeneration and the genetic factors that underlie genetic susceptibility. His email is richard_libby@urmc.rochester.edu
Howell GR, Libby RT, Jakobs TC, Phalan FC, Barter JW, Barbay JM, Smith RS, Wihtmore AV, Masland RH, John SWM. Submitted. Axons of retinal ganglion cells are insulted in the lamina early in a mouse glaucoma.
Jakobs TC, Libby RT, Ben Y, John SWM, Masland RH. 2005. Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol 171:313-325
Libby RT, Anderson MG, Pang I-H, Robinson Z, Savinova OV, Cosma IM, Snow A, Wilson LA, Smith RS, Clark AF, John SWM. 2005. Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration. Vis Neurosci 22: 637-648
Libby RT, Yan L, Savinova OV, Barter J, Smith RS, Nickells RW, John SWM. 2005. Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage. PLoS Genet 1: 17-26 http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pgen.0010004
Anderson MG, Libby RT, Gould DB, Smith RS, John SWM. 2005. High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma. Proc Natl Acad Sci USA 102: 4566-4571 http://www.pnas.org/cgi/content/full/102/12/4566
Libby RT, Smith RS, Savinova OV, Zabaleta A, Martin JE, Gonzalez FJ, John SWM. 2003. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science 299: 1578-1581 http://www.sciencemag.org/cgi/content/full/299/5612/1578?ijkey=RnOYI2djaEVuI&keytype=ref&siteid=sci
Back to staff page.
