Matthew Lavail, PhD
Professor Emeritus
Anatomy
School of Medicine

We have been involved in several lines of research aimed at modulating the rate of photoreceptor degeneration by both genetic and environmental means; to develop mutant rhodopsin transgenic rat models with which to study various forms of therapy; to study the efficacy of neurotrophic factors in slowing the progression of degeneration; to understand the cellular and molecular mechanisms of injury-induced protection; to develop gene-based delivery of neurotrophic factors; and to develop gene-based ribozyme therapy for the treatment of dominantly inherited disorders. Much of our current research stems from our original observation that bFGF can slow photoreceptor degeneration in RCS rats with inherited retinal dystrophy, the first such pharmaceutical effect in retinal degenerations, and that various growth factors, neurotrophins and cytokines, can protect photoreceptors from cell death due to excessive light. Most recently, we have been studying the role of the Unfolded Protein Response in inherited and environmentally induced retinal degenerations.

• Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by adeno-associated virus delivery of Stanniocalcin-1.
  Experimental eye research 2017 Roddy GW, Yasumura D, Matthes MT, Alavi MV, Boye SL, Rosa RH, Fautsch MP, Hauswirth WW, LaVail MM
• Sphingolipid profile alters in retinal dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration.
  Journal of lipid research 2016 Stiles M, Qi H, Sun E, Tan J, Porter H, Allegood J, Chalfant CE, Yasumura D, Matthes MT, LaVail MM, Mandal NA
• Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial.
  Human genetics 2016 Ghazi NG, Abboud EB, Nowilaty SR, Alkuraya H, Alhommadi A, Cai H, Hou R, Deng WT, Boye SL, Almaghamsi A, Al Saikhan F, Al-Dhibi H, Birch D, Chung C, Colak D, LaVail MM, Vollrath D, Erger K, Wang W, …
• Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.
  Advances in experimental medicine and biology 2016 Chiang WC, Joseph V, Yasumura D, Matthes MT, Lewin AS, Gorbatyuk MS, Ahern K, LaVail MM, Lin JH
• Gene Therapy for MERTK-Associated Retinal Degenerations.
  Advances in experimental medicine and biology 2016 LaVail MM, Yasumura D, Matthes MT, Yang H, Hauswirth WW, Deng WT, Vollrath D
• Tyro3 Modulates Mertk-Associated Retinal Degeneration.
  PLoS genetics 2015 Vollrath D, Yasumura D, Benchorin G, Matthes MT, Feng W, Nguyen NM, Sedano CD, Calton MA, LaVail MM
• Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows Photoreceptor Cell Degeneration.
  Investigative ophthalmology & visual science 2015 Murray SF, Jazayeri A, Matthes MT, Yasumura D, Yang H, Peralta R, Watt A, Freier S, Hung G, Adamson PS, Guo S, Monia BP, LaVail MM, McCaleb ML
• In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse.
  Investigative ophthalmology & visual science 2015 Alavi MV, Chiang WC, Kroeger H, Yasumura D, Matthes MT, Iwawaki T, LaVail MM, Gould DB, Lin JH
• Genotypic and phenotypic characterization of P23H line 1 rat model.
  PloS one 2015 Orhan E, Dalkara D, Neuillé M, Lechauve C, Michiels C, Picaud S, Léveillard T, Sahel JA, Naash MI, Lavail MM, Zeitz C, Audo I
• Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration.
  Molecular neurobiology 2014 Chiang WC, Kroeger H, Sakami S, Messah C, Yasumura D, Matthes MT, Coppinger JA, Palczewski K, LaVail MM, Lin JH
• Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress-induced cell death during the unfolded protein response.
  Molecular biology of the cell 2014 Hiramatsu N, Messah C, Han J, LaVail MM, Kaufman RJ, Lin JH
• Endoplasmic reticulum stress in vertebrate mutant rhodopsin models of retinal degeneration.
  Advances in experimental medicine and biology 2014 Kroeger H, LaVail MM, Lin JH
• Glutamatergic neurotransmission from melanopsin retinal ganglion cells is required for neonatal photoaversion but not adult pupillary light reflex.
  PloS one 2013 Delwig A, Majumdar S, Ahern K, LaVail MM, Edwards R, Hnasko TS, Copenhagen DR
• Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease.
  PloS one 2013 Li M, Yasumura D, Ma AA, Matthes MT, Yang H, Nielson G, Huang Y, Szoka FC, Lavail MM, Diamond MI
• Induction of endoplasmic reticulum stress genes, BiP and chop, in genetic and environmental models of retinal degeneration.
  Investigative ophthalmology & visual science 2012 Kroeger H, Messah C, Ahern K, Gee J, Joseph V, Matthes MT, Yasumura D, Gorbatyuk MS, Chiang WC, LaVail MM, Lin JH
• Optomotor and immunohistochemical changes in the juvenile S334ter rat.
  Experimental eye research 2012 McGill TJ, Prusky GT, Luna G, LaVail MM, Fisher SK, Lewis GP
• Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease.
  Investigative ophthalmology & visual science 2012 McGill TJ, Prusky GT, Douglas RM, Yasumura D, Matthes MT, Lowe RJ, Duncan JL, Yang H, Ahern K, Daniello KM, Silver B, LaVail MM
• Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats.
  Investigative ophthalmology & visual science 2012 Deng WT, Dinculescu A, Li Q, Boye SL, Li J, Gorbatyuk MS, Pang J, Chiodo VA, Matthes MT, Yasumura D, Liu L, Alkuraya FS, Zhang K, Vollrath D, LaVail MM, Hauswirth WW
• ER stress in retinal degeneration in S334ter Rho rats.
  PloS one 2012 Shinde VM, Sizova OS, Lin JH, LaVail MM, Gorbatyuk MS
• Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration.
  Molecular therapy : the journal of the American Society of Gene Therapy 2012 Roddy GW, Rosa RH, Oh JY, Ylostalo JH, Bartosh TJ, Choi H, Lee RH, Yasumura D, Ahern K, Nielsen G, Matthes MT, LaVail MM, Prockop DJ
• Ceramide signaling in retinal degeneration.
  Advances in experimental medicine and biology 2012 Chen H, Tran JT, Brush RS, Saadi A, Rahman AK, Yu M, Yasumura D, Matthes MT, Ahern K, Yang H, LaVail MM, Mandal MN
• Functional rescue of P23H rhodopsin photoreceptors by gene delivery.
  Advances in experimental medicine and biology 2012 Gorbatyuk MS, Gorbatyuk OS, LaVail MM, Lin JH, Hauswirth WW, Lewin AS
• Regeneration of cone outer segments induced by CNTF.
  Advances in experimental medicine and biology 2012 Wen R, Tao W, Luo L, Huang D, Kauper K, Stabila P, LaVail MM, Laties AM, Li Y
• Suppression of rds expression by siRNA and gene replacement strategies for gene therapy using rAAV vector.
  Advances in experimental medicine and biology 2012 Petrs-Silva H, Yasumura D, Matthes MT, LaVail MM, Lewin AS, Hauswirth WW
• An ENU-induced mutation in the Mertk gene (Mertknmf12) leads to a slow form of retinal degeneration.
  Investigative ophthalmology & visual science 2011 Maddox DM, Hicks WL, Vollrath D, LaVail MM, Naggert JK, Nishina PM
• mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice.
  The Journal of clinical investigation 2010 Zhao C, Yasumura D, Li X, Matthes M, Lloyd M, Nielsen G, Ahern K, Snyder M, Bok D, Dunaief JL, LaVail MM, Vollrath D
• Candidate genes for chromosomes 6 and 10 quantitative trait loci for age-related retinal degeneration in mice.
  Molecular vision 2010 Ogando DG, Dahlquist KD, Alizadeh M, Kunchithapautham K, Li J, Yu N, LaVail MM, Rohrer B, Vollrath D, Danciger M
• Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78.
  Proceedings of the National Academy of Sciences of the United States of America 2010 Gorbatyuk MS, Knox T, LaVail MM, Gorbatyuk OS, Noorwez SM, Hauswirth WW, Lin JH, Muzyczka N, Lewin AS
• CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration.
  PloS one 2010 Li Y, Tao W, Luo L, Huang D, Kauper K, Stabila P, Lavail MM, Laties AM, Wen R
• Intense cyclic light-induced retinal degeneration in rats.
  Archives of ophthalmology (Chicago, Ill. : 1960) 2010 Duncan JL, LaVail MM
• Misfolded proteins and retinal dystrophies.
  Advances in experimental medicine and biology 2010 Lin JH, Lavail MM
• Regulation of neonatal development of retinal ganglion cell dendrites by neurotrophin-3 overexpression.
  The Journal of comparative neurology 2009 Liu X, Robinson ML, Schreiber AM, Wu V, Lavail MM, Cang J, Copenhagen DR
• Sustained delivery of NT-3 from lens fiber cells in transgenic mice reveals specificity of neuroprotection in retinal degenerations.
  The Journal of comparative neurology 2008 Lavail MM, Nishikawa S, Duncan JL, Yang H, Matthes MT, Yasumura D, Vollrath D, Overbeek PA, Ash JD, Robinson ML
• The relationship of photoreceptor degeneration to retinal vascular development and loss in mutant rhodopsin transgenic and RCS rats.
  Experimental eye research 2008 Pennesi ME, Nishikawa S, Matthes MT, Yasumura D, LaVail MM
• Retinal TrkB receptors regulate neural development in the inner, but not outer, retina.
  Molecular and cellular neurosciences 2008 Grishanin RN, Yang H, Liu X, Donohue-Rolfe K, Nune GC, Zang K, Xu B, Duncan JL, Lavail MM, Copenhagen DR, Reichardt LF
• Genetic modifiers of retinal degeneration in the rd3 mouse.
  Investigative ophthalmology & visual science 2008 Danciger M, Ogando D, Yang H, Matthes MT, Yu N, Ahern K, Yasumura D, Williams RW, Lavail MM
• Intraocular CNTF reduces vision in normal rats in a dose-dependent manner.
  Investigative ophthalmology & visual science 2007 McGill TJ, Prusky GT, Douglas RM, Yasumura D, Matthes MT, Nune G, Donohue-Rolfe K, Yang H, Niculescu D, Hauswirth WW, Girman SV, Lund RD, Duncan JL, LaVail MM
• IRE1 signaling affects cell fate during the unfolded protein response.
  Science (New York, N.Y.) 2007 Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P
• Rapid and stable knockdown of an endogenous gene in retinal pigment epithelium.
  Human gene therapy 2007 Paskowitz DM, Greenberg KP, Yasumura D, Grimm D, Yang H, Duncan JL, Kay MA, Lavail MM, Flannery JG, Vollrath D
• Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2007 Johnson J, Fremeau RT, Duncan JL, Rentería RC, Yang H, Hua Z, Liu X, LaVail MM, Edwards RH, Copenhagen DR
• Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa.
  Investigative ophthalmology & visual science 2007 Rhee KD, Ruiz A, Duncan JL, Hauswirth WW, Lavail MM, Bok D, Yang XJ
• A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6.
  Investigative ophthalmology & visual science 2007 Smit-McBride Z, Oltjen SL, Lavail MM, Hjelmeland LM
• Neurotrophic factors minimize the retinal toxicity of verteporfin photodynamic therapy.
  Investigative ophthalmology & visual science 2007 Paskowitz DM, Donohue-Rolfe KM, Yang H, Yasumura D, Matthes MT, Hosseini K, Graybeal CM, Nune G, Zarbin MA, Lavail MM, Duncan JL
• Retinal damage caused by photodynamic therapy can be reduced using BDNF.
  Advances in experimental medicine and biology 2006 Duncan JL, Paskowitz DM, Nune GC, Yasumura D, Yang H, Matthes MT, Zarbin MA, LaVail MM
• Survival factors for treatment of retinal degenerative disorders: preclinical gains and issues for translation into clinical studies.
  Retina (Philadelphia, Pa.) 2005 Lavail MM
• Constant light-induced retinal damage and the RPE65-MET450 variant: assessment of the NZW/LacJ mouse.
  Molecular vision 2005 Danciger M, Yang H, Handschumacher L, LaVail MM
• BDNF reduces the retinal toxicity of verteporfin photodynamic therapy.
  Investigative ophthalmology & visual science 2004 Paskowitz DM, Nune G, Yasumura D, Yang H, Bhisitkul RB, Sharma S, Matthes MT, Zarbin MA, Lavail MM, Duncan JL
• Timing and topography of cell genesis in the rat retina.
  The Journal of comparative neurology 2004 Rapaport DH, Wong LL, Wood ED, Yasumura D, LaVail MM
• Range of retinal diseases potentially treatable by AAV-vectored gene therapy.
  Novartis Foundation symposium 2004 Hauswirth WW, Li Q, Raisler B, Timmers AM, Berns KI, Flannery JG, LaVail MM, Lewin AS
• Retinal remodeling triggered by photoreceptor degenerations.
  The Journal of comparative neurology 2003 Jones BW, Watt CB, Frederick JM, Baehr W, Chen CK, Levine EM, Milam AH, Lavail MM, Marc RE
• Free radical trap phenyl-N-tert-butylnitrone protects against light damage but does not rescue P23H and S334ter rhodopsin transgenic rats from inherited retinal degeneration.
  The Journal of neuroscience : the official journal of the Society for Neuroscience 2003 Ranchon I, LaVail MM, Kotake Y, Anderson RE
• A strong and highly significant QTL on chromosome 6 that protects the mouse from age-related retinal degeneration.
  Investigative ophthalmology & visual science 2003 Danciger M, Lyon J, Worrill D, LaVail MM, Yang H
• An RCS-like retinal dystrophy phenotype in mer knockout mice.
  Investigative ophthalmology & visual science 2003 Duncan JL, LaVail MM, Yasumura D, Matthes MT, Yang H, Trautmann N, Chappelow AV, Feng W, Earp HS, Matsushima GK, Vollrath D
• Inherited retinal dystrophy in Mer knockout mice.
  Advances in experimental medicine and biology 2003 Duncan JL, Yang H, Vollrath D, Yasumura D, Matthes MT, Trautmann N, Chappelow AV, Feng W, Earp HS, Matsushima GK, LaVail MM
• Photoreceptor degeneration in Pro23His and S334ter transgenic rats.
  Advances in experimental medicine and biology 2003 Lee D, Geller S, Walsh N, Valter K, Yasumura D, Matthes M, LaVail M, Stone J
• Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation.
  Experimental eye research 2002 Bok D, Yasumura D, Matthes MT, Ruiz A, Duncan JL, Chappelow AV, Zolutukhin S, Hauswirth W, LaVail MM
• Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells.
  The Journal of biological chemistry 2002 Feng W, Yasumura D, Matthes MT, LaVail MM, Vollrath D