Richard T. Libby, Ph.D.

Richard T. Libby, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 659
Rochester, NY 14642

Research Bio

Research Overview
Glaucoma is a complex group of diseases where many different genetic and environmental factors conspire to cause vision loss. While there are many different causes of glaucoma, the ultimate cause of vision loss in all glaucomas is the death of retinal ganglion cells (RGCs), the output neurons of the retina. Therefore, glaucoma is a neurodegeneration. Our lab focuses on the neurobiology of glaucoma. Primarily, we use mouse models of glaucoma and advanced mouse genetics to probe the pathophysiology of glaucoma. Specifically, we are interested in understanding the molecular processes that lead to RGC death in glaucoma and why are RGCs more likely to die in some patients than in others.



Cell Death Pathways Active in Glaucoma
To date, no molecules are known to be necessary for glaucomatous neurodegeneration nor has the initial molecular trigger(s) been identified. Identifying the molecular pathways required for RGC death in glaucoma will answer fundamental questions about neuronal pathophysiology and will identify potential therapeutic targets for the treatment of optic neuropathies. To determine the molecular degeneration cascades active in glaucoma we are taking two approaches. (1) Candidate gene analysis. The neurotrophic deprivation pathway (as one example) has been implicated as a critical pathway for glaucomatous RGC death. At both the protein and RNA level, we found that components of this pathway (e.g. BIM, JUN, and JNKs) are present in glaucomatous DBA/2J mice, suggesting that this pathway contributes to RGC death. Currently using our knowledge of the key mediator of somal apoptosis in DBA/2J glaucoma (BAX activation) and the other molecules that have been impacted in glaucoma, we are attempting to 'back track' our way up the RGC degeneration pathway. Eventually we hope this approach will lead to a complete identification of the somal and axonal degeneration pathways and to the initial molecular trigger(s) in glaucoma. (2) Genomic analysis. We are also using microarray analysis to investigate DBA/2J glaucoma. Microarray analysis has the potential to identify molecules involved in glaucomatous neurodegeneration that could not be predicted from current knowledge. In these experiments, gene expression changes at various, distinct stages of DBA/2J glaucomatous neurodegeneration are being examined.

Neuronal Susceptibility Factors
Elevated intraocular pressure is the best known risk factor for glaucoma. However, there is extensive patient variability in what constitutes pathogenic intraocular pressure (IOP), suggesting that other susceptibility factors are important in glaucoma. Therefore, even though glaucoma is clearly associated with IOP, susceptibility factors intrinsic to the RGCs and/or other retinal cells are likely critical mediators of glaucomatous neurodegeneration. We are attempting to define the genetic susceptibility factors that conspire with IOP to determine the probability of developing glaucoma and/or the severity of glaucoma. For instance we have shown that deficiencies in BAX gene dosage (a key molecule in the glaucomatous RGC degeneration pathway) can slow RGC loss in glaucomatous mice. These data suggest that allelic differences in components of the RGC degeneration pathway may contribute to glaucoma pathology. Also, we have been addressing the effect of blood pressure on glaucoma by backcrossing a null allele of angiotensin receptor 1 (Agtr1; deficiency in Agtr1 lowers blood pressure in mice) into DBA/2J. Low blood pressure in DBA/2J mice significantly increases the rate of glaucomatous neurodegeneration. Therefore, it appears that many diverse genetic factors can contribute to glaucomatous neurodegeneration and that the DBA/2J mouse is an effective tool in identifying these factors.

Awards & Honors (Local)

Research to Prevent Blindness Career Development Award. 2006 - 2010
David Bryant Trust. Unlocking Mechanisms Behind Vision Loss in Glaucoma. 2005
Lewis Rudin Glaucoma Prize. Awarded by The New York Academy of Medicine for the "most outstanding article on glaucoma published during the previous year". First author of article. 2004
Donald J. White Teaching Excellence Award. Awarded four times for my work as a teaching assistant in the lecture course, Introduction to Biology, Boston College. 1993,1995,1996,1997 1993 - 1997

Recent Journal Articles

Showing the 5 most recent journal articles. 54 available »

2014 Sep
Fernandes KA, Harder JM, John SW, Shrager P, Libby RT. "DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury." Neurobiology of disease.. 2014 Sep; 69:108-16. Epub 2014 May 27.
2014 Mar 1
Coleman JA, Zhu X, Djajadi HR, Molday LL, Smith RS, Libby RT, John SW, Molday RS. "Phospholipid flippase ATP8A2 is required for normal visual and auditory function and photoreceptor and spiral ganglion cell survival." Journal of cell science.. 2014 Mar 1; 127(Pt 5):1138-49. Epub 2014 Jan 10.
2014 Feb
Strazzeri JM, Hunter JJ, Masella BD, Yin L, Fischer WS, Diloreto DA, Libby RT, Williams DR, Merigan WH. "Focal damage to macaque photoreceptors produces persistent visual loss." Experimental eye research.. 2014 Feb; 119:88-96. Epub 2013 Dec 05.
2014
Huang L, Hu F, Xie X, Harder J, Fernandes K, Zeng XY, Libby R, Gan L. "Pou4f1 and pou4f2 are dispensable for the long-term survival of adult retinal ganglion cells in mice." PloS one. 2014 9(4):e94173. Epub 2014 Apr 15.
2014
Soto I, Howell GR, John CW, Kief JL, Libby RT, John SW. "DBA/2J Mice Are Susceptible to Diabetic Nephropathy and Diabetic Exacerbation of IOP Elevation." PloS one. 2014 9(9):e107291. Epub 2014 Sep 10.

Current Appointments

Associate Professor - Department of Ophthalmology (SMD) - Primary
Associate Professor - Department of Biomedical Genetics (SMD)
Associate Professor - Center for Visual Science A&S (RC)

Education

Doctorate in Biology | Boston College1997
Postdoctoral Fellow | Attended 2001 - 2005
Postdoctoral Scientist | Attended 1998 - 2001
Bachelor of Science in Biology | Villanova UniversityAttended 1986 - 1990
Assistant Professor | Attended 2006 - Present

Post-Doctoral Training & Residency

Postdoctoral Fellow in Dr. Simon John's Laboratory. The Jackson Laboratory, Bar Harbor, ME. Neurodegeneration in Glaucoma. 2005