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Matthew Lavail, PhD

TitleProfessor Emeritus
InstitutionUniversity of California San Francisco
DepartmentAnatomy
Address10 Koret Way
San Francisco CA 94143
Phone415-476-4233
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    Collapse Overview 
    Collapse Overview
    The focus of our laboratory is photoreceptor degeneration, the cause of blinding diseases such as retinitis pigmentosa, which affects approximately 1:3, 500 people worldwide, and age-related macular degeneration, which affects vision in the elderly in as many as 1:3 by the age of 75. Virtually no widely accepted forms of therapy exist for these diseases. 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.


    Collapse Research 
    Collapse Research Activities and Funding
    Models of Retinal Degeneration
    NIH/NEI R01EY006842Sep 30, 1986 - Nov 30, 2015
    Role: Principal Investigator
    BREEDING COLONY WITH INHERITED RETINAL DYSTROPHY
    NIH/NEI U01EY006842Sep 30, 1986 - Mar 31, 1992
    Role: Principal Investigator
    LIGHT DAMAGE TO NORMAL AND MUTANT RETINAS
    NIH/NEI R01EY004753Apr 1, 1983 - Mar 31, 1993
    Role: Principal Investigator
    Cellular Mechanisms of Inherited Retinal Degeneration
    NIH/NEI R01EY001919Jul 1, 1978 - Nov 30, 2015
    Role: Principal Investigator
    CELLULAR MECHANISMS OF INHERITED RETINAL DEGENERATION
    NIH/NEI R37EY001919Jul 1, 1978 - Feb 28, 1999
    Role: Principal Investigator
    P30 - CENTER CORE GRANT FOR VISION RESEARCH
    NIH/NEI P30EY002162Dec 1, 1977 - Jun 30, 2019
    Role: Principal Investigator
    PIGMENT EPITHELIUM INTERACTIONS WITH NEURAL RETINA
    NIH/NEI R37EY001429Sep 1, 1977 - Aug 31, 1998
    Role: Principal Investigator
    PIGMENT EPITHELIUM INTERACTIONS WITH NEURAL RETINA
    NIH/NEI R01EY001429Sep 1, 1977 - Aug 31, 1987
    Role: Principal Investigator

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    Collapse Global Health
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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Bryda EC, LaVail MM. Letter to the editor announcing the availability of RCS and transgenic rats with P23H and S334ter rhodopsin mutations with inherited retinal degenerations. Exp Eye Res. 2018 Oct 06; 178:176. PMID: 30296413.
      View in: PubMed
    2. Roddy GW, Yl?stalo JH, Fautsch MP, LaVail MM. RE: "Letter to the Editor concerning Roddy et al. Exp Eye Res 165:175-181, 2017". Exp Eye Res. 2018 Apr; 169:173. PMID: 29382537.
      View in: PubMed
    3. LaVail MM, Nishikawa S, Steinberg RH, Naash MI, Duncan JL, Trautmann N, Matthes MT, Yasumura D, Lau-Villacorta C, Chen J, Peterson WM, Yang H, Flannery JG. Phenotypic characterization of P23H and S334ter rhodopsin transgenic rat models of inherited retinal degeneration. Exp Eye Res. 2018 Feb; 167:56-90. PMID: 29122605.
      View in: PubMed
    4. Roddy GW, Yasumura D, Matthes MT, Alavi MV, Boye SL, Rosa RH, Fautsch MP, Hauswirth WW, LaVail MM. Long-term photoreceptor rescue in two rodent models of retinitis pigmentosa by adeno-associated virus delivery of Stanniocalcin-1. Exp Eye Res. 2017 12; 165:175-181. PMID: 28974356.
      View in: PubMed
    5. Stiles M, Qi H, Sun E, Tan J, Porter H, Allegood J, Chalfant CE, Yasumura D, Matthes MT, LaVail MM, Mandal NA. Sphingolipid profile alters in retinal dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration. J Lipid Res. 2016 05; 57(5):818-31. PMID: 26947037; PMCID: PMC4847629 [Available on 05/01/17].
    6. 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, Conlon T, Zhang K, Hauswirth W, Alkuraya FS. Treatment of retinitis pigmentosa due to MERTK mutations by ocular subretinal injection of adeno-associated virus gene vector: results of a phase I trial. Hum Genet. 2016 Mar; 135(3):327-43. PMID: 26825853.
      View in: PubMed
    7. LaVail MM, Yasumura D, Matthes MT, Yang H, Hauswirth WW, Deng WT, Vollrath D. Gene Therapy for MERTK-Associated Retinal Degenerations. Adv Exp Med Biol. 2016; 854:487-93. PMID: 26427450; PMCID: PMC4942279.
    8. Chiang WC, Joseph V, Yasumura D, Matthes MT, Lewin AS, Gorbatyuk MS, Ahern K, LaVail MM, Lin JH. Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin. Adv Exp Med Biol. 2016; 854:185-91. PMID: 26427410; PMCID: PMC4731204.
    9. Vollrath D, Yasumura D, Benchorin G, Matthes MT, Feng W, Nguyen NM, Sedano CD, Calton MA, LaVail MM. Tyro3 Modulates Mertk-Associated Retinal Degeneration. PLoS Genet. 2015 Dec; 11(12):e1005723. PMID: 26656104; PMCID: PMC4687644.
    10. 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. Allele-Specific Inhibition of Rhodopsin With an Antisense Oligonucleotide Slows Photoreceptor Cell Degeneration. Invest Ophthalmol Vis Sci. 2015 Oct; 56(11):6362-75. PMID: 26436889.
      View in: PubMed
    11. Alavi MV, Chiang WC, Kroeger H, Yasumura D, Matthes MT, Iwawaki T, LaVail MM, Gould DB, Lin JH. In Vivo Visualization of Endoplasmic Reticulum Stress in the Retina Using the ERAI Reporter Mouse. Invest Ophthalmol Vis Sci. 2015 Oct; 56(11):6961-70. PMID: 26513501; PMCID: PMC4627472.
    12. Orhan E, Dalkara D, Neuillé M, Lechauve C, Michiels C, Picaud S, Léveillard T, Sahel JA, Naash MI, Lavail MM, Zeitz C, Audo I. Genotypic and phenotypic characterization of P23H line 1 rat model. PLoS One. 2015; 10(5):e0127319. PMID: 26009893.
      View in: PubMed
    13. Chiang WC, Kroeger H, Sakami S, Messah C, Yasumura D, Matthes MT, Coppinger JA, Palczewski K, LaVail MM, Lin JH. Robust Endoplasmic Reticulum-Associated Degradation of Rhodopsin Precedes Retinal Degeneration. Mol Neurobiol. 2015 Aug; 52(1):679-95. PMID: 25270370; PMCID: PMC4383737.
    14. Hiramatsu N, Messah C, Han J, LaVail MM, Kaufman RJ, Lin JH. Translational and posttranslational regulation of XIAP by eIF2a and ATF4 promotes ER stress-induced cell death during the unfolded protein response. Mol Biol Cell. 2014 May; 25(9):1411-20. PMID: 24623724; PMCID: PMC4004591.
    15. Kroeger H, LaVail MM, Lin JH. Endoplasmic reticulum stress in vertebrate mutant rhodopsin models of retinal degeneration. Adv Exp Med Biol. 2014; 801:585-92. PMID: 24664747; PMCID: PMC4103620.
    16. Delwig A, Majumdar S, Ahern K, LaVail MM, Edwards R, Hnasko TS, Copenhagen DR. Glutamatergic neurotransmission from melanopsin retinal ganglion cells is required for neonatal photoaversion but not adult pupillary light reflex. PLoS One. 2013; 8(12):e83974. PMID: 24391855; PMCID: PMC3877098.
    17. Li M, Yasumura D, Ma AA, Matthes MT, Yang H, Nielson G, Huang Y, Szoka FC, Lavail MM, Diamond MI. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease. PLoS One. 2013; 8(2):e56026. PMID: 23409115; PMCID: PMC3569418.
    18. Kroeger H, Messah C, Ahern K, Gee J, Joseph V, Matthes MT, Yasumura D, Gorbatyuk MS, Chiang WC, LaVail MM, Lin JH. Induction of endoplasmic reticulum stress genes, BiP and chop, in genetic and environmental models of retinal degeneration. Invest Ophthalmol Vis Sci. 2012 Nov 09; 53(12):7590-9. PMID: 23074209; PMCID: PMC3495601.
    19. McGill TJ, Prusky GT, Luna G, LaVail MM, Fisher SK, Lewis GP. Optomotor and immunohistochemical changes in the juvenile S334ter rat. Exp Eye Res. 2012 Nov; 104:65-73. PMID: 23036564; PMCID: PMC3509745.
    20. McGill TJ, Prusky GT, Douglas RM, Yasumura D, Matthes MT, Lowe RJ, Duncan JL, Yang H, Ahern K, Daniello KM, Silver B, LaVail MM. Discordant anatomical, electrophysiological, and visual behavioral profiles of retinal degeneration in rat models of retinal degenerative disease. Invest Ophthalmol Vis Sci. 2012 Sep 14; 53(10):6232-44. PMID: 22899760; PMCID: PMC3444210.
    21. 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. Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats. Invest Ophthalmol Vis Sci. 2012 Apr 06; 53(4):1895-904. PMID: 22408006; PMCID: PMC3995567.
    22. Shinde VM, Sizova OS, Lin JH, LaVail MM, Gorbatyuk MS. ER stress in retinal degeneration in S334ter Rho rats. PLoS One. 2012; 7(3):e33266. PMID: 22432009; PMCID: PMC3303830.
    23. 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. Stanniocalcin-1 rescued photoreceptor degeneration in two rat models of inherited retinal degeneration. Mol Ther. 2012 Apr; 20(4):788-97. PMID: 22294148; PMCID: PMC3321604.
    24. Gorbatyuk MS, Gorbatyuk OS, LaVail MM, Lin JH, Hauswirth WW, Lewin AS. Functional rescue of P23H rhodopsin photoreceptors by gene delivery. Adv Exp Med Biol. 2012; 723:191-7. PMID: 22183333; PMCID: PMC3365920.
    25. Wen R, Tao W, Luo L, Huang D, Kauper K, Stabila P, LaVail MM, Laties AM, Li Y. Regeneration of cone outer segments induced by CNTF. Adv Exp Med Biol. 2012; 723:93-9. PMID: 22183320; PMCID: PMC3552642.
    26. Chen H, Tran JT, Brush RS, Saadi A, Rahman AK, Yu M, Yasumura D, Matthes MT, Ahern K, Yang H, LaVail MM, Mandal MN. Ceramide signaling in retinal degeneration. Adv Exp Med Biol. 2012; 723:553-8. PMID: 22183377; PMCID: PMC3552639.
    27. Petrs-Silva H, Yasumura D, Matthes MT, LaVail MM, Lewin AS, Hauswirth WW. Suppression of rds expression by siRNA and gene replacement strategies for gene therapy using rAAV vector. Adv Exp Med Biol. 2012; 723:215-23. PMID: 22183336; PMCID: PMC3556273.
    28. Maddox DM, Hicks WL, Vollrath D, LaVail MM, Naggert JK, Nishina PM. An ENU-induced mutation in the Mertk gene (Mertknmf12) leads to a slow form of retinal degeneration. Invest Ophthalmol Vis Sci. 2011 Jul 01; 52(7):4703-9. PMID: 21436282; PMCID: PMC3175976.
    29. Zhao C, Yasumura D, Li X, Matthes M, Lloyd M, Nielsen G, Ahern K, Snyder M, Bok D, Dunaief JL, LaVail MM, Vollrath D. mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice. J Clin Invest. 2011 Jan; 121(1):369-83. PMID: 21135502; PMCID: PMC3007156.
    30. Ogando DG, Dahlquist KD, Alizadeh M, Kunchithapautham K, Li J, Yu N, LaVail MM, Rohrer B, Vollrath D, Danciger M. Candidate genes for chromosomes 6 and 10 quantitative trait loci for age-related retinal degeneration in mice. Mol Vis. 2010 Jun 05; 16:1004-18. PMID: 20577653; PMCID: PMC2890552.
    31. Gorbatyuk MS, Knox T, LaVail MM, Gorbatyuk OS, Noorwez SM, Hauswirth WW, Lin JH, Muzyczka N, Lewin AS. Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci U S A. 2010 Mar 30; 107(13):5961-6. PMID: 20231467; PMCID: PMC2851865.
    32. Li Y, Tao W, Luo L, Huang D, Kauper K, Stabila P, Lavail MM, Laties AM, Wen R. CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. PLoS One. 2010 Mar 02; 5(3):e9495. PMID: 20209167; PMCID: PMC2830484.
    33. Duncan JL, LaVail MM. Intense cyclic light-induced retinal degeneration in rats. Arch Ophthalmol. 2010 Feb; 128(2):244-5. PMID: 20142550; PMCID: PMC4863714.
    34. Lin JH, Lavail MM. Misfolded proteins and retinal dystrophies. Adv Exp Med Biol. 2010; 664:115-21. PMID: 20238009; PMCID: PMC2955894.
    35. Liu X, Robinson ML, Schreiber AM, Wu V, Lavail MM, Cang J, Copenhagen DR. Regulation of neonatal development of retinal ganglion cell dendrites by neurotrophin-3 overexpression. J Comp Neurol. 2009 Jun 10; 514(5):449-58. PMID: 19350645; PMCID: PMC2691146.
    36. Lavail MM, Nishikawa S, Duncan JL, Yang H, Matthes MT, Yasumura D, Vollrath D, Overbeek PA, Ash JD, Robinson ML. Sustained delivery of NT-3 from lens fiber cells in transgenic mice reveals specificity of neuroprotection in retinal degenerations. J Comp Neurol. 2008 Dec 20; 511(6):724-35. PMID: 18925574; PMCID: PMC2702994.
    37. Pennesi ME, Nishikawa S, Matthes MT, Yasumura D, LaVail MM. The relationship of photoreceptor degeneration to retinal vascular development and loss in mutant rhodopsin transgenic and RCS rats. Exp Eye Res. 2008 Dec; 87(6):561-70. PMID: 18848932; PMCID: PMC3541029.
    38. Grishanin RN, Yang H, Liu X, Donohue-Rolfe K, Nune GC, Zang K, Xu B, Duncan JL, Lavail MM, Copenhagen DR, Reichardt LF. Retinal TrkB receptors regulate neural development in the inner, but not outer, retina. Mol Cell Neurosci. 2008 Jul; 38(3):431-43. PMID: 18511296; PMCID: PMC2849660.
    39. Danciger M, Ogando D, Yang H, Matthes MT, Yu N, Ahern K, Yasumura D, Williams RW, Lavail MM. Genetic modifiers of retinal degeneration in the rd3 mouse. Invest Ophthalmol Vis Sci. 2008 Jul; 49(7):2863-9. PMID: 18344445; PMCID: PMC2574750.
    40. 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. Intraocular CNTF reduces vision in normal rats in a dose-dependent manner. Invest Ophthalmol Vis Sci. 2007 Dec; 48(12):5756-66. PMID: 18055829.
      View in: PubMed
    41. Lin JH, Li H, Yasumura D, Cohen HR, Zhang C, Panning B, Shokat KM, Lavail MM, Walter P. IRE1 signaling affects cell fate during the unfolded protein response. Science. 2007 Nov 09; 318(5852):944-9. PMID: 17991856; PMCID: PMC3670588.
    42. Paskowitz DM, Greenberg KP, Yasumura D, Grimm D, Yang H, Duncan JL, Kay MA, Lavail MM, Flannery JG, Vollrath D. Rapid and stable knockdown of an endogenous gene in retinal pigment epithelium. Hum Gene Ther. 2007 Oct; 18(10):871-80. PMID: 17892416.
      View in: PubMed
    43. Johnson J, Fremeau RT, Duncan JL, Rentería RC, Yang H, Hua Z, Liu X, LaVail MM, Edwards RH, Copenhagen DR. Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions. J Neurosci. 2007 Jul 04; 27(27):7245-55. PMID: 17611277; PMCID: PMC2443709.
    44. Rhee KD, Ruiz A, Duncan JL, Hauswirth WW, Lavail MM, Bok D, Yang XJ. Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2007 Mar; 48(3):1389-400. PMID: 17325188.
      View in: PubMed
    45. Smit-McBride Z, Oltjen SL, Lavail MM, Hjelmeland LM. A strong genetic determinant of hyperoxia-related retinal degeneration on mouse chromosome 6. Invest Ophthalmol Vis Sci. 2007 Jan; 48(1):405-11. PMID: 17197561.
      View in: PubMed
    46. Paskowitz DM, Donohue-Rolfe KM, Yang H, Yasumura D, Matthes MT, Hosseini K, Graybeal CM, Nune G, Zarbin MA, Lavail MM, Duncan JL. Neurotrophic factors minimize the retinal toxicity of verteporfin photodynamic therapy. Invest Ophthalmol Vis Sci. 2007 Jan; 48(1):430-7. PMID: 17197564.
      View in: PubMed
    47. Duncan JL, Paskowitz DM, Nune GC, Yasumura D, Yang H, Matthes MT, Zarbin MA, LaVail MM. Retinal damage caused by photodynamic therapy can be reduced using BDNF. Adv Exp Med Biol. 2006; 572:297-302. PMID: 17249587.
      View in: PubMed
    48. Lavail MM. Survival factors for treatment of retinal degenerative disorders: preclinical gains and issues for translation into clinical studies. Retina. 2005 Dec; 25(8 Suppl):S25-S26. PMID: 16374321.
      View in: PubMed
    49. Danciger M, Yang H, Handschumacher L, LaVail MM. Constant light-induced retinal damage and the RPE65-MET450 variant: assessment of the NZW/LacJ mouse. Mol Vis. 2005 May 27; 11:374-9. PMID: 15947737.
      View in: PubMed
    50. Paskowitz DM, Nune G, Yasumura D, Yang H, Bhisitkul RB, Sharma S, Matthes MT, Zarbin MA, Lavail MM, Duncan JL. BDNF reduces the retinal toxicity of verteporfin photodynamic therapy. Invest Ophthalmol Vis Sci. 2004 Nov; 45(11):4190-6. PMID: 15505074.
      View in: PubMed
    51. Rapaport DH, Wong LL, Wood ED, Yasumura D, LaVail MM. Timing and topography of cell genesis in the rat retina. J Comp Neurol. 2004 Jun 21; 474(2):304-24. PMID: 15164429.
      View in: PubMed
    52. Hauswirth WW, Li Q, Raisler B, Timmers AM, Berns KI, Flannery JG, LaVail MM, Lewin AS. Range of retinal diseases potentially treatable by AAV-vectored gene therapy. Novartis Found Symp. 2004; 255:179-88; discussion 188-94. PMID: 14750604.
      View in: PubMed
    53. Jones BW, Watt CB, Frederick JM, Baehr W, Chen CK, Levine EM, Milam AH, Lavail MM, Marc RE. Retinal remodeling triggered by photoreceptor degenerations. J Comp Neurol. 2003 Sep 08; 464(1):1-16. PMID: 12866125.
      View in: PubMed
    54. Ranchon I, LaVail MM, Kotake Y, Anderson 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. J Neurosci. 2003 Jul 09; 23(14):6050-7. PMID: 12853423.
      View in: PubMed
    55. Danciger M, Lyon J, Worrill D, LaVail MM, Yang H. A strong and highly significant QTL on chromosome 6 that protects the mouse from age-related retinal degeneration. Invest Ophthalmol Vis Sci. 2003 Jun; 44(6):2442-9. PMID: 12766041.
      View in: PubMed
    56. Duncan JL, LaVail MM, Yasumura D, Matthes MT, Yang H, Trautmann N, Chappelow AV, Feng W, Earp HS, Matsushima GK, Vollrath D. An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest Ophthalmol Vis Sci. 2003 Feb; 44(2):826-38. PMID: 12556419.
      View in: PubMed
    57. Lee D, Geller S, Walsh N, Valter K, Yasumura D, Matthes M, LaVail M, Stone J. Photoreceptor degeneration in Pro23His and S334ter transgenic rats. Adv Exp Med Biol. 2003; 533:297-302. PMID: 15180276.
      View in: PubMed
    58. Duncan JL, Yang H, Vollrath D, Yasumura D, Matthes MT, Trautmann N, Chappelow AV, Feng W, Earp HS, Matsushima GK, LaVail MM. Inherited retinal dystrophy in Mer knockout mice. Adv Exp Med Biol. 2003; 533:165-72. PMID: 15180261.
      View in: PubMed
    59. Anderson RE, Maude MB, McClellan M, Matthes MT, Yasumura D, LaVail MM. Low docosahexaenoic acid levels in rod outer segments of rats with P23H and S334ter rhodopsin mutations. Mol Vis. 2002 Sep 23; 8:351-8. PMID: 12355064.
      View in: PubMed
    60. Bok D, Yasumura D, Matthes MT, Ruiz A, Duncan JL, Chappelow AV, Zolutukhin S, Hauswirth W, LaVail MM. Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation. Exp Eye Res. 2002 Jun; 74(6):719-35. PMID: 12126945.
      View in: PubMed
    61. Feng W, Yasumura D, Matthes MT, LaVail MM, Vollrath D. Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J Biol Chem. 2002 May 10; 277(19):17016-22. PMID: 11861639.
      View in: PubMed