Edward M. Levine, Ph.D.


Faculty Appointments
Professor of Ophthalmology and Visual Sciences Professor of Cell and Developmental BiologyWilliam A. Black Chair in Ophthalmology
Ph.D., Molecular Biology, State University of New York, Stony Brook, New YorkB.S., Biology, State University of New York, Albany, New York
Office Address
MCN B3222
1161 21st Ave South
Nashville, TN 37232
Research Description
My laboratory addresses two areas of importance to vision. In the first, we study the cellular and molecular mechanisms governing mouse retinal development, from the initial patterning events of the optic neuroepithelium through specification of cell fate in the proliferative and multipotential retinal progenitor cells and their postmitotic progeny. Our work incorporates multiple genetic models that are helping us to identify the genetic circuitry driving these processes. The second topic is to understand how the resident retinal glia (Muller glia) contribute to the pathological changes associated with retinal disease and injury, and to discover ways to stimulate regeneration from these cells. We are particularly interested in understanding how the Muller glia alter their differentiation program in retinal injury and proliferative vitreoretinopathy as these situations best reveal the complexity of the barriers to regeneration. Through the Audacious Goals Initiative from the National Eye Institute, we have begun a screen to identify novel factors that promote regenerative properties in adult mouse Muller glia in vivo. Our research incorporates mouse genetics, cell and tissue culture, analyses of protein and nucleic acid expression, imaging, and examination of cellular behavior.
Research Keywords
Mammalian Retinal Development and Regeneration Tissue formation Growth control Cell fate control Stem cells and Progenitor cells
Sigulinsky CL, Li X, Levine EM. Expression of Sonic Hedgehog and pathway components in the embryonic mouse head: anatomical relationships between regulators of positive and negative feedback. BMC Res Notes. 2021 Aug 8/5/2021; 14(1): 300. PMID: 34353359, PMCID: PMC8340441, PII: 10.1186/s13104-021-05714-5, DOI: 10.1186/s13104-021-05714-5, ISSN: 1756-0500.

Didiano D, Abner JJ, Hinger SA, Flickinger Z, Kent M, Clement MA, Balaiya S, Liu Q, Dai X, Levine EM, Patton JG. Induction of a proliferative response in the zebrafish retina by injection of extracellular vesicles. Exp Eye Res [print-electronic]. 2020 Nov; 200: 108254. PMID: 32961174, PMCID: PMC7655690, PII: S0014-4835(20)30512-1, DOI: 10.1016/j.exer.2020.108254, ISSN: 1096-0007.

Webster MK, Barnett BJ, Stanchfield ML, Paris JR, Webster SE, Cooley-Themm CA, Levine EM, Otteson DC, Linn CL. Stimulation of Retinal Pigment Epithelium With an a7 nAChR Agonist Leads to Müller Glia Dependent Neurogenesis in the Adult Mammalian Retina. Invest Ophthalmol Vis Sci. 2019 Feb 2/1/2019; 60(2): 570-9. PMID: 30721274, PMCID: PMC6363405, PII: 2724307, DOI: 10.1167/iovs.18-25722, ISSN: 1552-5783.

Moon KH, Kim HT, Lee D, Rao MB, Levine EM, Lim DS, Kim JW. Differential Expression of NF2 in Neuroepithelial Compartments Is Necessary for Mammalian Eye Development. Dev. Cell [print-electronic]. 2018 Jan 1/8/2018; 44(1): 13-28.e3. PMID: 29249622, PMCID: PMC5760287, PII: S1534-5807(17)30945-0, DOI: 10.1016/j.devcel.2017.11.011, ISSN: 1878-1551.

Wohl SG, Jorstad NL, Levine EM, Reh TA. Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture. Nat Commun. 2017 Nov 11/17/2017; 8(1): 1603. PMID: 29150673, PMCID: PMC5693933, PII: 10.1038/s41467-017-01624-y, DOI: 10.1038/s41467-017-01624-y, ISSN: 2041-1723.

Xie Y, Kaufmann D, Moulton MJ, Panahi S, Gaynes JA, Watters HN, Zhou D, Xue HH, Fung CM, Levine EM, Letsou A, Brennan KC, Dorsky RI. Lef1-dependent hypothalamic neurogenesis inhibits anxiety. PLoS Biol. 2017 Aug; 15(8): e2002257. PMID: 28837622, PII: pbio.2002257, DOI: 10.1371/journal.pbio.2002257, ISSN: 1545-7885.

Kim Y, Lim S, Ha T, Song YH, Sohn YI, Park DJ, Paik SS, Kim-Kaneyama JR, Song MR, Leung A, Levine EM, Kim IB, Goo YS, Lee SH, Kang KH, Kim JW. The LIM protein complex establishes a retinal circuitry of visual adaptation by regulating Pax6 a-enhancer activity. Elife. 2017 Jan 1/31/2017; 6: PMID: 28139974, PMCID: PMC5308899, DOI: 10.7554/eLife.21303, ISSN: 2050-084X.

Gaynes JA, Otsuna H, Campbell DS, Manfredi JP, Levine EM, Chien CB. The RNA Binding Protein Igf2bp1 Is Required for Zebrafish RGC Axon Outgrowth In Vivo. PLoS ONE. 2015; 10(9): e0134751. PMID: 26325373, PMCID: PMC4556669, PII: PONE-D-15-05090, DOI: 10.1371/journal.pone.0134751, ISSN: 1932-6203.

Sigulinsky CL, German ML, Leung AM, Clark AM, Yun S, Levine EM. Genetic chimeras reveal the autonomy requirements for Vsx2 in embryonic retinal progenitor cells. Neural Dev. 2015; 10: 12. PMID: 25927996, PMCID: PMC4450477, PII: 10.1186/s13064-015-0039-5, DOI: 10.1186/s13064-015-0039-5, ISSN: 1749-8104.

Fuhrmann S, Zou C, Levine EM. Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp. Eye Res [print-electronic]. 2014 Jun; 123: 141-50. PMID: 24060344, PMCID: PMC4087157, PII: S0014-4835(13)00269-8, DOI: 10.1016/j.exer.2013.09.003, ISSN: 1096-0007.

Gordon PJ, Yun S, Clark AM, Monuki ES, Murtaugh LC, Levine EM. Lhx2 balances progenitor maintenance with neurogenic output and promotes competence state progression in the developing retina. J. Neurosci. 2013 Jul 7/24/2013; 33(30): 12197-207. PMID: 23884928, PMCID: PMC3721834, PII: 33/30/12197, DOI: 10.1523/JNEUROSCI.1494-13.2013, ISSN: 1529-2401.

Pollak J, Wilken MS, Ueki Y, Cox KE, Sullivan JM, Taylor RJ, Levine EM, Reh TA. ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors. Development [print-electronic]. 2013 Jun; 140(12): 2619-31. PMID: 23637330, PMCID: PMC3666387, PII: dev.091355, DOI: 10.1242/dev.091355, ISSN: 1477-9129.

Heynen SR, Meneau I, Caprara C, Samardzija M, Imsand C, Levine EM, Grimm C. CDC42 is required for tissue lamination and cell survival in the mouse retina. PLoS ONE [print-electronic]. 2013; 8(1): e53806. PMID: 23372671, PMCID: PMC3553133, PII: PONE-D-12-14949, DOI: 10.1371/journal.pone.0053806, ISSN: 1932-6203.

Zou C, Levine EM. Vsx2 controls eye organogenesis and retinal progenitor identity via homeodomain and non-homeodomain residues required for high affinity DNA binding. PLoS Genet [print-electronic]. 2012 Sep; 8(9): e1002924. PMID: 23028343, PMCID: PMC3447932, PII: PGENETICS-D-12-01041, DOI: 10.1371/journal.pgen.1002924, ISSN: 1553-7404.

Das G, Clark AM, Levine EM. Cyclin D1 inactivation extends proliferation and alters histogenesis in the postnatal mouse retina. Dev. Dyn. 2012 May; 241(5): 941-52. PMID: 22434780, PMCID: PMC3361900, DOI: 10.1002/dvdy.23782, ISSN: 1097-0177.

Vázquez-Chona FR, Swan A, Ferrell WD, Jiang L, Baehr W, Chien WM, Fero M, Marc RE, Levine EM. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function. BMC Neurosci. 2011; 12: 98. PMID: 21985191, PMCID: PMC3203081, PII: 1471-2202-12-98, DOI: 10.1186/1471-2202-12-98, ISSN: 1471-2202.

Yun S, Saijoh Y, Hirokawa KE, Kopinke D, Murtaugh LC, Monuki ES, Levine EM. Lhx2 links the intrinsic and extrinsic factors that control optic cup formation. Development. 2009 Dec; 136(23): 3895-906. PMID: 19906857, PMCID: PMC2778739, PII: 136/23/3895, DOI: 10.1242/dev.041202, ISSN: 1477-9129.

Vázquez-Chona FR, Clark AM, Levine EM. Rlbp1 promoter drives robust Müller glial GFP expression in transgenic mice. Invest. Ophthalmol. Vis. Sci [print-electronic]. 2009 Aug; 50(8): 3996-4003. PMID: 19324864, PII: iovs.08-3189, DOI: 10.1167/iovs.08-3189, ISSN: 1552-5783.

Das G, Choi Y, Sicinski P, Levine EM. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. Neural Dev. 2009; 4: 15. PMID: 19416500, PMCID: PMC2694796, PII: 1749-8104-4-15, DOI: 10.1186/1749-8104-4-15, ISSN: 1749-8104.

Sigulinsky CL, Green ES, Clark AM, Levine EM. Vsx2/Chx10 ensures the correct timing and magnitude of Hedgehog signaling in the mouse retina. Dev. Biol [print-electronic]. 2008 May 5/15/2008; 317(2): 560-75. PMID: 18417110, PMCID: PMC2671289, PII: S0012-1606(08)00184-X, DOI: 10.1016/j.ydbio.2008.02.055, ISSN: 1095-564X.

Barton KM, Levine EM. Expression patterns and cell cycle profiles of PCNA, MCM6, cyclin D1, cyclin A2, cyclin B1, and phosphorylated histone H3 in the developing mouse retina. Dev. Dyn. 2008 Mar; 237(3): 672-82. PMID: 18265020, DOI: 10.1002/dvdy.21449, ISSN: 1058-8388.

Clark AM, Yun S, Veien ES, Wu YY, Chow RL, Dorsky RI, Levine EM. Negative regulation of Vsx1 by its paralog Chx10/Vsx2 is conserved in the vertebrate retina. Brain Res [print-electronic]. 2008 Feb 2/4/2008; 1192: 99-113. PMID: 17919464, PMCID: PMC3315787, PII: S0006-8993(07)01376-5, DOI: 10.1016/j.brainres.2007.06.007, ISSN: 0006-8993.

Defoe DM, Adams LB, Sun J, Wisecarver SN, Levine EM. Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation. Mol. Vis. 2007; 13: 273-86. PMID: 17356514, PMCID: PMC2633469, PII: v13/a31, ISSN: 1090-0535.

Dhomen NS, Balaggan KS, Pearson RA, Bainbridge JW, Levine EM, Ali RR, Sowden JC. Absence of chx10 causes neural progenitors to persist in the adult retina. Invest. Ophthalmol. Vis. Sci. 2006 Jan; 47(1): 386-96. PMID: 16384989, PMCID: PMC2423807, PII: 47/1/386, DOI: 10.1167/iovs.05-0428, ISSN: 0146-0404.

Levine EM. Cell cycling through development. Development. 2004 May; 131(10): 2241-6. PMID: 15128665, PII: 131/10/2241, DOI: 10.1242/dev.01180, ISSN: 0950-1991.

Levine EM, Green ES. Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors. Semin. Cell Dev. Biol. 2004 Feb; 15(1): 63-74. PMID: 15036209, PII: S1084-9521(03)00064-8, DOI: 10.1016/j.semcdb.2003.09.001, ISSN: 1084-9521.

Defoe DM, Levine EM. Expression of the cyclin-dependent kinase inhibitor p27Kip1 by developing retinal pigment epithelium. Gene Expr. Patterns. 2003 Oct; 3(5): 615-9. PMID: 12971995, PII: S1567133X03001200, ISSN: 1567-133X.

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 9/8/2003; 464(1): 1-16. PMID: 12866125, DOI: 10.1002/cne.10703, ISSN: 0021-9967.

Wu Y, Liu Y, Levine EM, Rao MS. Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors. Dev. Dyn. 2003 Apr; 226(4): 675-89. PMID: 12666205, DOI: 10.1002/dvdy.10278, ISSN: 1058-8388.

Green ES, Stubbs JL, Levine EM. Genetic rescue of cell number in a mouse model of microphthalmia: interactions between Chx10 and G1-phase cell cycle regulators. Development. 2003 Feb; 130(3): 539-52. PMID: 12490560, ISSN: 0950-1991.

Cunningham JJ, Levine EM, Zindy F, Goloubeva O, Roussel MF, Smeyne RJ. The cyclin-dependent kinase inhibitors p19(Ink4d) and p27(Kip1) are coexpressed in select retinal cells and act cooperatively to control cell cycle exit. Mol. Cell. Neurosci. 2002 Mar; 19(3): 359-74. PMID: 11906209, PII: S1044743101910905, DOI: 10.1006/mcne.2001.1090, ISSN: 1044-7431.

Fuhrmann S, Levine EM, Reh TA. Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development. 2000 Nov; 127(21): 4599-609. PMID: 11023863, ISSN: 0950-1991.

Levine EM, Close J, Fero M, Ostrovsky A, Reh TA. P27(Kip1) regulates cell cycle withdrawal of late multipotent progenitor cells in the mammalian retina. Dev. Biol. 2000 Mar 3/15/2000; 219(2): 299-314. PMID: 10694424, PII: S0012-1606(00)99622-2, DOI: 10.1006/dbio.2000.9622, ISSN: 0012-1606.

Levine EM, Fuhrmann S, Reh TA. Soluble factors and the development of rod photoreceptors. Cell. Mol. Life Sci. 2000 Feb; 57(2): 224-34. PMID: 10766019, PII: 10.1007/PL00000686, DOI: 10.1007/PL00000686, ISSN: 1420-682X.

Chow L, Levine EM, Reh TA. The nuclear receptor transcription factor, retinoid-related orphan receptor beta, regulates retinal progenitor proliferation. Mech. Dev. 1998 Oct; 77(2): 149-64. PMID: 9831642, PII: S092547739800135X, ISSN: 0925-4773.

Reh TA, Levine EM. Multipotential stem cells and progenitors in the vertebrate retina. J. Neurobiol. 1998 Aug; 36(2): 206-20. PMID: 9712305, PII: 10.1002/(SICI)1097-4695(199808)36:2<206::AID-NEU8>3.0.CO;2-5, ISSN: 0022-3034.

Passini MA, Levine EM, Canger AK, Raymond PA, Schechter N. Vsx-1 and Vsx-2: differential expression of two paired-like homeobox genes during zebrafish and goldfish retinogenesis. J. Comp. Neurol. 1997 Nov 11/24/1997; 388(3): 495-505. PMID: 9368856, PII: 10.1002/(SICI)1096-9861(19971124)388:3<495::AID-CNE11>3.0.CO;2-L, ISSN: 0021-9967.

Levine EM, Passini M, Hitchcock PF, Glasgow E, Schechter N. Vsx-1 and Vsx-2: two Chx10-like homeobox genes expressed in overlapping domains in the adult goldfish retina. J. Comp. Neurol. 1997 Oct 10/27/1997; 387(3): 439-48. PMID: 9335426, PII: 10.1002/(SICI)1096-9861(19971027)387:3<439::AID-CNE9>3.0.CO;2-1, ISSN: 0021-9967.

Levine EM, Roelink H, Turner J, Reh TA. Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J. Neurosci. 1997 Aug 8/15/1997; 17(16): 6277-88. PMID: 9236238, ISSN: 0270-6474.

Levine EM, Hitchcock PF, Glasgow E, Schechter N. Restricted expression of a new paired-class homeobox gene in normal and regenerating adult goldfish retina. J. Comp. Neurol. 1994 Oct 10/22/1994; 348(4): 596-606. PMID: 7836564, DOI: 10.1002/cne.903480409, ISSN: 0021-9967.

Glasgow E, Druger RK, Fuchs C, Levine EM, Giordano S, Schechter N. Cloning of multiple forms of goldfish vimentin: differential expression in CNS. J. Neurochem. 1994 Aug; 63(2): 470-81. PMID: 8035174, ISSN: 0022-3042.

Levine EM, Schechter N. Homeobox genes are expressed in the retina and brain of adult goldfish. Proc. Natl. Acad. Sci. U.S.A. 1993 Apr 4/1/1993; 90(7): 2729-33. PMID: 8096640, PMCID: PMC46169, ISSN: 0027-8424.

Druger RK, Levine EM, Glasgow E, Jones PS, Schechter N. Cloning of a type I keratin from goldfish optic nerve: differential expression of keratins during regeneration. Differentiation. 1992 Dec; 52(1): 33-43. PMID: 1283739, ISSN: 0301-4681.

Glasgow E, Druger RK, Levine EM, Fuchs C, Schechter N. Plasticin, a novel type III neurofilament protein from goldfish retina: increased expression during optic nerve regeneration. Neuron. 1992 Aug; 9(2): 373-81. PMID: 1379821, PII: 0896-6273(92)90175-D, ISSN: 0896-6273.