Richard Libby
| Title | Assistant Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Ophthalmology |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 659
Rochester NY 14642
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| 1993 |
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| 1997 | 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 | | 2004 |
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| 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. | | 2005 |
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| David Bryant Trust. Unlocking Mechanisms Behind Vision Loss in Glaucoma. | | 2006 |
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| 2010 | Research to Prevent Blindness Career Development Award. |
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.
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Harder JM, Libby RT. Deficiency in Bim, Bid and Bbc3 (Puma) do not prevent axonal injury induced death. Cell Death Differ. 2013 Jan; 20(1):182.
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Zhu X, Libby RT, de Vries WN, Smith RS, Wright DL, Bronson RT, Seburn KL, John SW. Mutations in a p-type ATPase gene cause axonal degeneration. PLoS Genet. 2012 Aug; 8(8):e1002853.
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Harder JM, Fernandes KA, Libby RT. The Bcl-2 family member BIM has multiple glaucoma-relevant functions in DBA/2J mice. Sci Rep. 2012; 2:530.
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Harder JM, Ding Q, Fernandes KA, Cherry JD, Gan L, Libby RT. BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells. Mol Cell Neurosci. 2012 Aug; 51(1-2):53-9.
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Howell GR, Soto I, Zhu X, Ryan M, Macalinao DG, Sousa GL, Caddle LB, Macnicoll KH, Barbay JM, Porciatti V, Anderson MG, Smith RS, Clark AF, Libby RT, John SW. Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma. J Clin Invest. 2012 Apr 2; 122(4):1246-61.
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Geng Y, Dubra A, Yin L, Merigan WH, Sharma R, Libby RT, Williams DR. Adaptive optics retinal imaging in the living mouse eye. Biomed Opt Express. 2012 Apr 1; 3(4):715-34.
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Fernandes KA, Harder JM, Fornarola LB, Freeman RS, Clark AF, Pang IH, John SW, Libby RT. JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death. Neurobiol Dis. 2012 May; 46(2):393-401.
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Howell GR, Walton DO, King BL, Libby RT, John SW. Datgan, a reusable software system for facile interrogation and visualization of complex transcription profiling data. BMC Genomics. 2011; 12:429.
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Harder JM, Libby RT. BBC3 (PUMA) regulates developmental apoptosis but not axonal injury induced death in the retina. Mol Neurodegener. 2011; 6:50.
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Xi X, McMillan DH, Lehmann GM, Sime PJ, Libby RT, Huxlin KR, Feldon SE, Phipps RP. Ocular fibroblast diversity: implications for inflammation and ocular wound healing. Invest Ophthalmol Vis Sci. 2011 Jun; 52(7):4859-65.
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Yin L, Greenberg K, Hunter JJ, Dalkara D, Kolstad KD, Masella BD, Wolfe R, Visel M, Stone D, Libby RT, Diloreto D, Schaffer D, Flannery J, Williams DR, Merigan WH. Intravitreal injection of AAV2 transduces macaque inner retina. Invest Ophthalmol Vis Sci. 2011 Apr; 52(5):2775-83.
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Lopes VS, Gibbs D, Libby RT, Aleman TS, Welch DL, Lillo C, Jacobson SG, Radu RA, Steel KP, Williams DS. The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65. Hum Mol Genet. 2011 Jul 1; 20(13):2560-70.
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Howell GR, Macalinao DG, Sousa GL, Walden M, Soto I, Kneeland SC, Barbay JM, King BL, Marchant JK, Hibbs M, Stevens B, Barres BA, Clark AF, Libby RT, John SW. Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma. J Clin Invest. 2011 Apr 1; 121(4):1429-44.
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Geng Y, Schery LA, Sharma R, Dubra A, Ahmad K, Libby RT, Williams DR. Optical properties of the mouse eye. Biomed Opt Express. 2011; 2(4):717-38.
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Feng L, Xie ZH, Ding Q, Xie X, Libby RT, Gan L. MATH5 controls the acquisition of multiple retinal cell fates. Mol Brain. 2010; 3:36.
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Libby RT, Gould DB. Endoplasmic reticulum stress as a primary pathogenic mechanism leading to age-related macular degeneration. Adv Exp Med Biol. 2010; 664:403-9.
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Bertram KM, Baglole CJ, Phipps RP, Libby RT. Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration. Am J Physiol Cell Physiol. 2009 Nov; 297(5):C1200-10.
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Scoles D, Gray DC, Hunter JJ, Wolfe R, Gee BP, Geng Y, Masella BD, Libby RT, Russell S, Williams DR, Merigan WH. In-vivo imaging of retinal nerve fiber layer vasculature: imaging histology comparison. BMC Ophthalmol. 2009; 9:9.
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Ding Q, Chen H, Xie X, Libby RT, Tian N, Gan L. BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons. J Neurosci. 2009 Apr 1; 29(13):3992-4003.
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Howell GR, Libby RT, John SW. Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection. Prog Brain Res. 2008; 173:303-21.
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Howell GR, Libby RT, Jakobs TC, Smith RS, Phalan FC, Barter JW, Barbay JM, Marchant JK, Mahesh N, Porciatti V, Whitmore AV, Masland RH, John SW. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol. 2007 Dec 31; 179(7):1523-37.
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Libby RT, Howell GR, Pang IH, Savinova OV, Mehalow AK, Barter JW, Smith RS, Clark AF, John SW. Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model. BMC Neurosci. 2007; 8:108.
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Howell GR, Libby RT, Marchant JK, Wilson LA, Cosma IM, Smith RS, Anderson MG, John SW. Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1. BMC Genet. 2007; 8:45.
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Anderson MG, Libby RT, Mao M, Cosma IM, Wilson LA, Smith RS, John SW. Genetic context determines susceptibility to intraocular pressure elevation in a mouse pigmentary glaucoma. BMC Biol. 2006; 4:20.
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Whitmore AV, Libby RT, John SW. Glaucoma: thinking in new ways-a rôle for autonomous axonal self-destruction and other compartmentalised processes? Prog Retin Eye Res. 2005 Nov; 24(6):639-62.
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Jakobs TC, Libby RT, Ben Y, John SW, Masland RH. Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. J Cell Biol. 2005 Oct 24; 171(2):313-25.
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Libby RT, Anderson MG, Pang IH, Robinson ZH, Savinova OV, Cosma IM, Snow A, Wilson LA, Smith RS, Clark AF, John SW. Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration. Vis Neurosci. 2005 Sep-Oct; 22(5):637-48.
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Libby RT, Li Y, Savinova OV, Barter J, Smith RS, Nickells RW, John SW. Susceptibility to neurodegeneration in a glaucoma is modified by Bax gene dosage. PLoS Genet. 2005 Jul; 1(1):17-26.
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Kitamoto J, Libby RT, Gibbs D, Steel KP, Williams DS. Myosin VI is required for normal retinal function. Exp Eye Res. 2005 Jul; 81(1):116-20.
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Anderson MG, Libby RT, Gould DB, Smith RS, John SW. High-dose radiation with bone marrow transfer prevents neurodegeneration in an inherited glaucoma. Proc Natl Acad Sci U S A. 2005 Mar 22; 102(12):4566-71.
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Libby RT, Gould DB, Anderson MG, John SW. Complex genetics of glaucoma susceptibility. Annu Rev Genomics Hum Genet. 2005; 6:15-44.
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Gibbs D, Azarian SM, Lillo C, Kitamoto J, Klomp AE, Steel KP, Libby RT, Williams DS. Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes. J Cell Sci. 2004 Dec 15; 117(Pt 26):6473-83.
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Libby RT, Lillo C, Kitamoto J, Williams DS, Steel KP. Myosin Va is required for normal photoreceptor synaptic activity. J Cell Sci. 2004 Sep 1; 117(Pt 19):4509-15.
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Libby RT, Kitamoto J, Holme RH, Williams DS, Steel KP. Cdh23 mutations in the mouse are associated with retinal dysfunction but not retinal degeneration. Exp Eye Res. 2003 Dec; 77(6):731-9.
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Libby RT, Smith RS, Savinova OV, Zabaleta A, Martin JE, Gonzalez FJ, John SW. Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science. 2003 Mar 7; 299(5612):1578-81.
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Warner CL, Stewart A, Luzio JP, Steel KP, Libby RT, Kendrick-Jones J, Buss F. Loss of myosin VI reduces secretion and the size of the Golgi in fibroblasts from Snell's waltzer mice. EMBO J. 2003 Feb 3; 22(3):569-79.
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Kros CJ, Marcotti W, van Netten SM, Self TJ, Libby RT, Brown SD, Richardson GP, Steel KP. Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations. Nat Neurosci. 2002 Jan; 5(1):41-7.
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La Spada AR, Fu YH, Sopher BL, Libby RT, Wang X, Li LY, Einum DD, Huang J, Possin DE, Smith AC, Martinez RA, Koszdin KL, Treuting PM, Ware CB, Hurley JB, Ptácek LJ, Chen S. Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron. 2001 Sep 27; 31(6):913-27.
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Libby RT, Steel KP. Electroretinographic anomalies in mice with mutations in Myo7a, the gene involved in human Usher syndrome type 1B. Invest Ophthalmol Vis Sci. 2001 Mar; 42(3):770-8.
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Libby RT, Champliaud MF, Claudepierre T, Xu Y, Gibbons EP, Koch M, Burgeson RE, Hunter DD, Brunken WJ. Laminin expression in adult and developing retinae: evidence of two novel CNS laminins. J Neurosci. 2000 Sep 1; 20(17):6517-28.
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Libby RT, Steel KP. The roles of unconventional myosins in hearing and deafness. Essays Biochem. 2000; 35:159-74.
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Libby RT, Brunken WJ, Hunter DD. Roles of the extracellular matrix in retinal development and maintenance. Results Probl Cell Differ. 2000; 31:115-40.
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Libby RT, Lavallee CR, Balkema GW, Brunken WJ, Hunter DD. Disruption of laminin beta2 chain production causes alterations in morphology and function in the CNS. J Neurosci. 1999 Nov 1; 19(21):9399-411.
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Graves SS, Goshorn SC, Stone DM, Axworthy DB, Reno JM, Bottino B, Searle S, Henry A, Pedersen J, Rees AR, Libby RT. Molecular modeling and preclinical evaluation of the humanized NR-LU-13 antibody. Clin Cancer Res. 1999 Apr; 5(4):899-908.
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Libby RT, Xu Y, Selfors LM, Brunken WJ, Hunter DD. Identification of the cellular source of laminin beta2 in adult and developing vertebrate retinae. J Comp Neurol. 1997 Dec 29; 389(4):655-67.
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Libby RT, Hunter DD, Brunken WJ. Developmental expression of laminin beta 2 in rat retina. Further support for a role in rod morphogenesis. Invest Ophthalmol Vis Sci. 1996 Jul; 37(8):1651-61.
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Libby RT, Nelson JL, Calvo JM, Gallant JA. Transcriptional proofreading in Escherichia coli. EMBO J. 1989 Oct; 8(10):3153-8.
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