Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice

Molecular Neurodegeneration

Abbot F Clark¹  Terry A Braun³  Robert J Wordinger¹  Benjamin P Faga³  David Thole²  Alex H Wagner³  Yang Liu¹  Colleen M McDowell¹  Tasneem P Sharma¹ 

[1] Department of Cell Biology & Immunology, NTERI, UNTHSC, Ft. Worth, TX USA;Center for Bioinformatics and Computational Biology, University of Iowa, Iowa, IA USA;Department of Biomedical Engineering, University of Iowa, Iowa, IA USA

关键词: Gene expression;    Microarray;    Regeneration;    Neurodegeneration;    Axotomy;    Apoptosis;    Retinal ganglion cell;    Optic nerve crush;    Central nervous system;   

Others  :  861606
DOI  :  10.1186/1750-1326-9-14

 received in 2013-12-19, accepted in 2014-04-18,  发布年份 2014

【 摘 要 】

Background

Central nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets.

Results

Only 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (≥1.5, ≤-1.5, p < 0.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR.

Conclusion

A number of detrimental gene expression changes occur that contribute to trauma-induced neurodegeneration after injury to ON axons. Nrn1 (synaptic plasticity gene), Synpr and Syt1 (synaptic vesicle fusion genes), and Vsnl1 (neuron differentiation associated gene) were a few of the potentially unique genes identified that were down-regulated spatially and temporally in our rodent ONC model. Bioinformatic meta-analysis identified significant tissue-specific and time-dependent gene clusters associated with regenerative changes, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. These ONC induced neuronal loss and regenerative failure associated clusters can be extrapolated to changes occurring in other forms of CNS trauma or in clinical neurodegenerative pathological settings. In conclusion, this study identified potential therapeutic targets to address two key mechanisms of CNS trauma and neurodegeneration: neuronal loss and regenerative failure.

【 授权许可】

   
2014 Sharma et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Schwartz M: Optic nerve crush: protection and regeneration. Brain Res Bull 2004, 62(6):467-471.
• [2]Ohlsson M, Mattsson P, Svensson M: A temporal study of axonal degeneration and glial scar formation following a standardized crush injury of the optic nerve in the adult rat. Restor Neurol Neurosci 2004, 22(1):1-10.
• [3]Magharious M, D’Onofrio PM, Hollander A, Zhu P, Chen J, Koeberle PD: Quantitative iTRAQ analysis of retinal ganglion cell degeneration after optic nerve crush. J Proteome Res 2011, 10(8):3344-3362.
• [4]Wohlfart G: Degeneration and regeneration in the nervous system. Recent advances. World Neurol 1961, 2:187-198.
• [5]Windle WF: Regeneration of axons in the vertebrate central nervous system. Physiol Rev 1956, 36(4):427-440.
• [6]Huber AB, Schwab ME: Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem 2000, 381(5–6):407-419.
• [7]Huber AB, Weinmann O, Brosamle C, Oertle T, Schwab ME: Patterns of Nogo mRNA and protein expression in the developing and adult rat and after CNS lesions. J Neurosci 2002, 22(9):3553-3567.
• [8]Filbin MT: Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 2003, 4(9):703-713.
• [9]Tang S, Qiu J, Nikulina E, Filbin MT: Soluble myelin-associated glycoprotein released from damaged white matter inhibits axonal regeneration. Mol Cell Neurosci 2001, 18(3):259-269.
• [10]Winzeler AM, Mandemakers WJ, Sun MZ, Stafford M, Phillips CT, Barres BA: The lipid sulfatide is a novel myelin-associated inhibitor of CNS axon outgrowth. J Neurosci 2011, 31(17):6481-6492.
• [11]Kopp MA, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing GJ, Strittmatter SM, Dirnagl U, Schwab JM: Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury. Cell Tissue Res 2012, 349(1):119-132.
• [12]Sandvig A, Berry M, Barrett LB, Butt A, Logan A: Myelin-, reactive glia-, and scar-derived CNS axon growth inhibitors: expression, receptor signaling, and correlation with axon regeneration. Glia 2004, 46(3):225-251.
• [13]Silver J, Miller JH: Regeneration beyond the glial scar. Nat Rev Neurosci 2004, 5(2):146-156.
• [14]Lawson LJ, Frost L, Risbridger J, Fearn S, Perry VH: Quantification of the mononuclear phagocyte response to Wallerian degeneration of the optic nerve. J Neurocytol 1994, 23(12):729-744.
• [15]Lazarov-Spiegler O, Rapalino O, Agranov G, Schwartz M: Restricted inflammatory reaction in the CNS: a key impediment to axonal regeneration? Mol Med Today 1998, 4(8):337-342.
• [16]Jaerve A, Muller HW: Chemokines in CNS injury and repair. Cell Tissue Res 2012, 349(1):229-248.
• [17]Monnier PP, D’Onofrio PM, Magharious M, Hollander AC, Tassew N, Szydlowska K, Tymianski M, Koeberle PD: Involvement of caspase-6 and caspase-8 in neuronal apoptosis and the regenerative failure of injured retinal ganglion cells. J Neurosci 2011, 31(29):10494-10505.
• [18]Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ: Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 1995, 36(5):774-786.
• [19]Li Y, Schlamp CL, Nickells RW: Experimental induction of retinal ganglion cell death in adult mice. Invest Ophthalmol Vis Sci 1999, 40(5):1004-1008.
• [20]Li Y, Semaan SJ, Schlamp CL, Nickells RW: Dominant inheritance of retinal ganglion cell resistance to optic nerve crush in mice. BMC Neurosci 2007, 8:19. BioMed Central Full Text
• [21]Barron KD, Dentinger MP, Krohel G, Easton SK, Mankes R: Qualitative and quantitative ultrastructural observations on retinal ganglion cell layer of rat after intraorbital optic nerve crush. J Neurocytol 1986, 15(3):345-362.
• [22]Templeton JP, Nassr M, Vazquez-Chona F, Freeman-Anderson NE, Orr WE, Williams RW, Geisert EE: Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush. BMC Neurosci 2009, 10:90. BioMed Central Full Text
• [23]Misantone LJ, Gershenbaum M, Murray M: Viability of retinal ganglion cells after optic nerve crush in adult rats. J Neurocytol 1984, 13(3):449-465.
• [24]Bahr M: Live or let die - retinal ganglion cell death and survival during development and in the lesioned adult CNS. Trends Neurosci 2000, 23(10):483-490.
• [25]Klocker N, Zerfowski M, Gellrich NC, Bahr M: Morphological and functional analysis of an incomplete CNS fiber tract lesion: graded crush of the rat optic nerve. J Neurosci Methods 2001, 110(1–2):147-153.
• [26]Agudo M, Perez-Marin MC, Lonngren U, Sobrado P, Conesa A, Canovas I, Salinas-Navarro M, Miralles-Imperial J, Hallbook F, Vidal-Sanz M: Time course profiling of the retinal transcriptome after optic nerve transection and optic nerve crush. Mol Vis 2008, 14:1050-1063.
• [27]Tang Z, Arjunan P, Lee C, Li Y, Kumar A, Hou X, Wang B, Wardega P, Zhang F, Dong L, Zhang Y, Zhang SZ, Ding H, Fariss RN, Becker KG, Lennartsson J, Nagai N, Cao Y, Li X: Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3beta phosphorylation. J Exp Med 2010, 207(4):867-880.
• [28]Lukas TJ, Wang AL, Yuan M, Neufeld AH: Early cellular signaling responses to axonal injury. Cell Commun Signal: CCS 2009, 7:5. BioMed Central Full Text
• [29]Qu J, Jakobs TC: The time course of gene expression during reactive gliosis in the optic nerve. PLoS One 2013, 8(6):e67094.
• [30]Sharma A, Pollett MA, Plant GW, Harvey AR: Changes in mRNA expression of class 3 semaphorins and their receptors in the adult rat retino-collicular system after unilateral optic nerve injury. Invest Ophthalmol Vis Sci 2012, 53(13):8367-8377.
• [31]Blaugrund E, Lavie V, Cohen I, Solomon A, Schreyer DJ, Schwartz M: Axonal regeneration is associated with glial migration: comparison between the injured optic nerves of fish and rats. J Comp Neurol 1993, 330(1):105-112.
• [32]Doster SK, Lozano AM, Aguayo AJ, Willard MB: Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury. Neuron 1991, 6(4):635-647.
• [33]Leon S, Yin Y, Nguyen J, Irwin N, Benowitz LI: Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci 2000, 20(12):4615-4626.
• [34]Ridet JL, Malhotra SK, Privat A, Gage FH: Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 1997, 20(12):570-577.
• [35]Dibas A, Oku H, Fukuhara M, Kurimoto T, Ikeda T, Patil RV, Sharif NA, Yorio T: Changes in ocular aquaporin expression following optic nerve crush. Mol Vis 2010, 16:330-340.
• [36]Woldemussie E, Wijono M, Ruiz G: Muller cell response to laser-induced increase in intraocular pressure in rats. Glia 2004, 47(2):109-119.
• [37]Parrilla-Reverter G, Agudo M, Nadal-Nicolas F, Alarcon-Martinez L, Jimenez-Lopez M, Salinas-Navarro M, Sobrado-Calvo P, Bernal-Garro JM, Villegas-Perez MP, Vidal-Sanz M: Time-course of the retinal nerve fibre layer degeneration after complete intra-orbital optic nerve transection or crush: a comparative study. Vis Res 2009, 49(23):2808-2825.
• [38]Koeberle PD, Bahr M: Growth and guidance cues for regenerating axons: where have they gone? J Neurobiol 2004, 59(1):162-180.
• [39]Kermer P, Klocker N, Bahr M: Neuronal death after brain injury. Models, mechanisms, and therapeutic strategies in vivo. Cell Tissue Res 1999, 298(3):383-395.
• [40]Koeberle PD, Gauldie J, Ball AK: Effects of adenoviral-mediated gene transfer of interleukin-10, interleukin-4, and transforming growth factor-beta on the survival of axotomized retinal ganglion cells. Neuroscience 2004, 125(4):903-920.
• [41]Kipnis J, Yoles E, Schori H, Hauben E, Shaked I, Schwartz M: Neuronal survival after CNS insult is determined by a genetically encoded autoimmune response. J Neurosci 2001, 21(13):4564-4571.
• [42]Isenmann S, Wahl C, Krajewski S, Reed JC, Bahr M: Up-regulation of Bax protein in degenerating retinal ganglion cells precedes apoptotic cell death after optic nerve lesion in the rat. Eur J Neurosci 1997, 9(8):1763-1772.
• [43]Kermer P, Ankerhold R, Klocker N, Krajewski S, Reed JC, Bahr M: Caspase-9: involvement in secondary death of axotomized rat retinal ganglion cells in vivo. Brain Res Mol Brain Res 2000, 85(1–2):144-150.
• [44]Kermer P, Klocker N, Labes M, Bahr M: Inhibition of CPP32-like proteases rescues axotomized retinal ganglion cells from secondary cell death in vivo. J Neurosci 1998, 18(12):4656-4662.
• [45]Kikuchi M, Tenneti L, Lipton SA: Role of p38 mitogen-activated protein kinase in axotomy-induced apoptosis of rat retinal ganglion cells. J Neurosci 2000, 20(13):5037-5044.
• [46]Galindo-Romero C, Aviles-Trigueros M, Jimenez-Lopez M, Valiente-Soriano FJ, Salinas-Navarro M, Nadal-Nicolas F, Villegas-Perez MP, Vidal-Sanz M, Agudo-Barriuso M: Axotomy-induced retinal ganglion cell death in adult mice: quantitative and topographic time course analyses. Exp Eye Res 2011, 92(5):377-387.
• [47]Kim BJ, Braun TA, Wordinger RJ, Clark AF: Progressive morphological changes and impaired retinal function associated with temporal regulation of gene expression after retinal ischemia/reperfusion injury in mice. Mol Neurodegener 2013, 8:21. BioMed Central Full Text
• [48]Xia Y, Chen J, Xiong L, Liu J, Liu X, Ma L, Zhang Q, You C, Chen J, Liu X, Wang X, Ju Y: Retinal whole genome microarray analysis and early morphological changes in the optic nerves of monkeys after an intraorbital nerve irradiated injury. Mol Vis 2011, 17:2920-2933.
• [49]Jehle T, Dimitriu C, Auer S, Knoth R, Vidal-Sanz M, Gozes I, Lagreze WA: The neuropeptide NAP provides neuroprotection against retinal ganglion cell damage after retinal ischemia and optic nerve crush. Albrecht Von Graefes Arch Klin Exp Ophthalmol 2008, 246(9):1255-1263.
• [50]Agudo M, Perez-Marin MC, Sobrado-Calvo P, Lonngren U, Salinas-Navarro M, Canovas I, Nadal-Nicolas FM, Miralles-Imperial J, Hallbook F, Vidal-Sanz M: Immediate upregulation of proteins belonging to different branches of the apoptotic cascade in the retina after optic nerve transection and optic nerve crush. Invest Ophthalmol Vis Sci 2009, 50(1):424-431.
• [51]Goldenberg-Cohen N, Dratviman-Storobinsky O, El Dadon Bar S, Cheporko Y, Hochhauser E: Protective effect of bax ablation against cell loss in the retinal ganglion layer induced by optic nerve crush in transgenic mice. J Neuroophthalmol 2011, 31(4):331-338.
• [52]Haverkamp S, Inta D, Monyer H, Wassle H: Expression analysis of green fluorescent protein in retinal neurons of four transgenic mouse lines. Neuroscience 2009, 160(1):126-139.
• [53]Raymond ID, Vila A, Huynh UC, Brecha NC: Cyan fluorescent protein expression in ganglion and amacrine cells in a thy1-CFP transgenic mouse retina. Mol Vis 2008, 14:1559-1574.
• [54]Masland RH: Neuronal diversity in the retina. Curr Opin Neurobiol 2001, 11(4):431-436.
• [55]Kim CY, Kuehn MH, Clark AF, Kwon YH: Gene expression profile of the adult human retinal ganglion cell layer. Mol Vis 2006, 12:1640-1648.
• [56]Villegas-Perez MP, Vidal-Sanz M, Rasminsky M, Bray GM, Aguayo AJ: Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats. J Neurobiol 1993, 24(1):23-36.
• [57]Nadal-Nicolas FM, Jimenez-Lopez M, Sobrado-Calvo P, Nieto-Lopez L, Canovas-Martinez I, Salinas-Navarro M, Vidal-Sanz M, Agudo M: Brn3a as a marker of retinal ganglion cells: qualitative and quantitative time course studies in naive and optic nerve-injured retinas. Invest Ophthalmol Vis Sci 2009, 50(8):3860-3868.
• [58]Berkelaar M, Clarke DB, Wang YC, Bray GM, Aguayo AJ: Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats. J Neurosci 1994, 14(7):4368-4374.
• [59]Aryee MJ, Gutierrez-Pabello JA, Kramnik I, Maiti T, Quackenbush J: An improved empirical bayes approach to estimating differential gene expression in microarray time-course data: BETR (Bayesian Estimation of Temporal Regulation). BMC Bioinforma 2009, 10:409. BioMed Central Full Text
• [60]Cantallops I, Haas K, Cline HT: Postsynaptic CPG15 promotes synaptic maturation and presynaptic axon arbor elaboration in vivo. Nat Neurosci 2000, 3(10):1004-1011.
• [61]Carpenter S: Proximal axonal enlargement in motor neuron disease. Neurology 1968, 18(9):841-851.
• [62]Delisle MB, Carpenter S: Neurofibrillary axonal swellings and amyotrophic lateral sclerosis. J Neurol Sci 1984, 63(2):241-250.
• [63]Ishii T, Haga S, Tokutake S: Presence of neurofilament protein in Alzheimer’s neurofibrillary tangles (ANT). An immunofluorescent study. Acta Neuropathol 1979, 48(2):105-112.
• [64]Nukina N, Kosik KS, Selkoe DJ: Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein. Proc Natl Acad Sci U S A 1987, 84(10):3415-3419.
• [65]Hill WD, Arai M, Cohen JA, Trojanowski JQ: Neurofilament mRNA is reduced in Parkinson’s disease substantia nigra pars compacta neurons. J Comp Neurol 1993, 329(3):328-336.
• [66]Fabrizi GM, Cavallaro T, Angiari C, Bertolasi L, Cabrini I, Ferrarini M, Rizzuto N: Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E. Neurology 2004, 62(8):1429-1431.
• [67]Bigio EH, Lipton AM, White CL 3rd, Dickson DW, Hirano A: Frontotemporal and motor neurone degeneration with neurofilament inclusion bodies: additional evidence for overlap between FTD and ALS. Neuropathol Appl Neurobiol 2003, 29(3):239-253.
• [68]Cairns NJ, Perry RH, Jaros E, Burn D, McKeith IG, Lowe JS, Holton J, Rossor MN, Skullerud K, Duyckaerts C, Cruz-Sanchez FF, Lantos PL: Patients with a novel neurofilamentopathy: dementia with neurofilament inclusions. Neurosci Lett 2003, 341(3):177-180.
• [69]Josephs KA, Holton JL, Rossor MN, Braendgaard H, Ozawa T, Fox NC, Petersen RC, Pearl GS, Ganguly M, Rosa P, Laursen H, Parisi JE, Waldemar G, Quinn NP, Dickson DW, Revesz T: Neurofilament inclusion body disease: a new proteinopathy? Brain 2003, 126(Pt 10):2291-2303.
• [70]Asbury AK, Gale MK, Cox SC, Baringer JR, Berg BO: Giant axonal neuropathy–a unique case with segmental neurofilamentous masses. Acta Neuropathol 1972, 20(3):237-247.
• [71]Medori R, Autilio-Gambetti L, Monaco S, Gambetti P: Experimental diabetic neuropathy: impairment of slow transport with changes in axon cross-sectional area. Proc Natl Acad Sci U S A 1985, 82(22):7716-7720.
• [72]Medori R, Jenich H, Autilio-Gambetti L, Gambetti P: Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models. J Neurosci 1988, 8(5):1814-1821.
• [73]Perrot R, Berges R, Bocquet A, Eyer J: Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration. Mol Neurobiol 2008, 38(1):27-65.
• [74]Huang X, Kong W, Zhou Y, Gregori G: Distortion of axonal cytoskeleton: an early sign of glaucomatous damage. Invest Ophthalmol Vis Sci 2011, 52(6):2879-2888.
• [75]Ivanov D, Dvoriantchikova G, Nathanson L, McKinnon SJ, Shestopalov VI: Microarray analysis of gene expression in adult retinal ganglion cells. FEBS Lett 2006, 580(1):331-335.
• [76]Farkas RH, Qian J, Goldberg JL, Quigley HA, Zack DJ: Gene expression profiling of purified rat retinal ganglion cells. Invest Ophthalmol Vis Sci 2004, 45(8):2503-2513.
• [77]Grabs D, Bergmann M, Schuster T, Fox PA, Brich M, Gratz M: Differential expression of synaptophysin and synaptoporin during pre- and postnatal development of the rat hippocampal network. Eur J Neurosci 1994, 6(11):1765-1771.
• [78]Singec I, Knoth R, Ditter M, Hagemeyer CE, Rosenbrock H, Frotscher M, Volk B: Synaptic vesicle protein synaptoporin is differently expressed by subpopulations of mouse hippocampal neurons. J Comp Neurol 2002, 452(2):139-153.
• [79]Sun T, Xiao HS, Zhou PB, Lu YJ, Bao L, Zhang X: Differential expression of synaptoporin and synaptophysin in primary sensory neurons and up-regulation of synaptoporin after peripheral nerve injury. Neuroscience 2006, 141(3):1233-1245.
• [80]Greif KF, Asabere N, Lutz GJ, Gallo G: Synaptotagmin-1 promotes the formation of axonal filopodia and branches along the developing axons of forebrain neurons. Dev Neurobiol 2013, 73(1):27-44.
• [81]Malarkey EB, Parpura V: Temporal characteristics of vesicular fusion in astrocytes: examination of synaptobrevin 2-laden vesicles at single vesicle resolution. J Physiol 2011, 589(Pt 17):4271-4300.
• [82]Jeon CJ, Strettoi E, Masland RH: The major cell populations of the mouse retina. J Neurosci 1998, 18(21):8936-8946.
• [83]Quina LA, Pak W, Lanier J, Banwait P, Gratwick K, Liu Y, Velasquez T, O’Leary DD, Goulding M, Turner EE: Brn3a-expressing retinal ganglion cells project specifically to thalamocortical and collicular visual pathways. J Neurosci 2005, 25(50):11595-11604.
• [84]Johnson TV, Martin KR: Development and characterization of an adult retinal explant organotypic tissue culture system as an in vitro intraocular stem cell transplantation model. Invest Ophthalmol Vis Sci 2008, 49(8):3503-3512.
• [85]Fujino T, Wu Z, Lin WC, Phillips MA, Nedivi E: cpg15 and cpg15-2 constitute a family of activity-regulated ligands expressed differentially in the nervous system to promote neurite growth and neuronal survival. J Comp Neurol 2008, 507(5):1831-1845.
• [86]Kigerl KA, McGaughy VM, Popovich PG: Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J Comp Neurol 2006, 494(4):578-594.
• [87]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, 1(1):17-26.
• [88]Montalban-Soler L, Alarcon-Martinez L, Jimenez-Lopez M, Salinas-Navarro M, Galindo-Romero C, Bezerra de Sa F, Garcia-Ayuso D, Aviles-Trigueros M, Vidal-Sanz M, Agudo-Barriuso M, Villegas-Pérez MP: Retinal compensatory changes after light damage in albino mice. Mol Vis 2012, 18:675-693.
• [89]Garcia-Ayuso D, Salinas-Navarro M, Agudo-Barriuso M, Alarcon-Martinez L, Vidal-Sanz M, Villegas-Perez MP: Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration. Mol Vis 2011, 17:1716-1733.
• [90]McCurley AT, Callard GV: Time course analysis of gene expression patterns in zebrafish eye during optic nerve regeneration. J Exp Neurosci 2010, 2010(4):17-33.
• [91]Agudo-Barriuso M, Lahoz A, Nadal-Nicolas FM, Sobrado-Calvo P, Piquer-Gil M, Diaz-Llopis M, Vidal-Sanz M, Mullor JL: Metabolomic changes in the rat retina after optic nerve crush. Invest Ophthalmol Vis Sci 2013, 54(6):4249-4259.
• [92]Liedtke T, Naskar R, Eisenacher M, Thanos S: Transformation of adult retina from the regenerative to the axonogenesis state activates specific genes in various subsets of neurons and glial cells. Glia 2007, 55(2):189-201.
• [93]Munguba GC, Geisert EE, Williams RW, Tapia ML, Lam DK, Bhattacharya SK, Lee RK: Effects of glaucoma on Chrna6 expression in the retina. Curr Eye Res 2013, 38(1):150-157.
• [94]Yuan A, Rao MV, Sasaki T, Chen Y, Kumar A, Veeranna , Liem RK, Eyer J, Peterson AC, Julien JP, Nixon RA: Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J Neurosci 2006, 26(39):10006-10019.
• [95]Kielczewski JL, Pease ME, Quigley HA: The effect of experimental glaucoma and optic nerve transection on amacrine cells in the rat retina. Invest Ophthalmol Vis Sci 2005, 46(9):3188-3196.
• [96]Kirsch M, Trautmann N, Ernst M, Hofmann HD: Involvement of gp130-associated cytokine signaling in Muller cell activation following optic nerve lesion. Glia 2010, 58(7):768-779.
• [97]Aldskogius H, Kozlova EN: Central neuron-glial and glial-glial interactions following axon injury. Prog Neurobiol 1998, 55(1):1-26.
• [98]Bernstein HG, Baumann B, Danos P, Diekmann S, Bogerts B, Gundelfinger ED, Braunewell KH: Regional and cellular distribution of neural visinin-like protein immunoreactivities (VILIP-1 and VILIP-3) in human brain. J Neurocytol 1999, 28(8):655-662.
• [99]Braunewell KH, Klein-Szanto AJ: Visinin-like proteins (VSNLs): interaction partners and emerging functions in signal transduction of a subfamily of neuronal Ca2 + − sensor proteins. Cell Tissue Res 2009, 335(2):301-316.
• [100]De Raad S, Comte M, Nef P, Lenz SE, Gundelfinger ED, Cox JA: Distribution pattern of three neural calcium-binding proteins (NCS-1, VILIP and recoverin) in chicken, bovine and rat retina. Histochem J 1995, 27(7):524-535.
• [101]Yao JJ, Gao XF, Chow CW, Zhan XQ, Hu CL, Mei YA: Neuritin activates insulin receptor pathway to up-regulate Kv4.2-mediated transient outward K + current in rat cerebellar granule neurons. J Biol Chem 2012, 287(49):41534-41545.
• [102]Nedivi E, Wu GY, Cline HT: Promotion of dendritic growth by CPG15, an activity-induced signaling molecule. Science 1998, 281(5384):1863-1866.
• [103]Fujino T, Leslie JH, Eavri R, Chen JL, Lin WC, Flanders GH, Borok E, Horvath TL, Nedivi E: CPG15 regulates synapse stability in the developing and adult brain. Genes Dev 2011, 25(24):2674-2685.
• [104]Naeve GS, Ramakrishnan M, Kramer R, Hevroni D, Citri Y, Theill LE: Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc Natl Acad Sci U S A 1997, 94(6):2648-2653.
• [105]Nedivi E, Fieldust S, Theill LE, Hevron D: A set of genes expressed in response to light in the adult cerebral cortex and regulated during development. Proc Natl Acad Sci U S A 1996, 93(5):2048-2053.
• [106]Javaherian A, Cline HT: Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron 2005, 45(4):505-512.
• [107]Cappelletti G, Galbiati M, Ronchi C, Maggioni MG, Onesto E, Poletti A: Neuritin (cpg15) enhances the differentiating effect of NGF on neuronal PC12 cells. J Neurosci Res 2007, 85(12):2702-2713.
• [108]Fainzilber M, Budnik V, Segal RA, Kreutz MR: From synapse to nucleus and back again–communication over distance within neurons. J Neurosci 2011, 31(45):16045-16048.
• [109]Li JY, Dahlstrom A: Axonal transport of synaptic vesicle proteins in the rat optic nerve. J Neurobiol 1997, 32(2):237-250.
• [110]Kwon KB, Kim JS, Chang BJ: Translocational changes of localization of synapsin in axonal sprouts of regenerating rat sciatic nerves after ligation crush injury. J Vet Sci 2000, 1(1):1-9.
• [111]Morfini G, Szebenyi G, Elluru R, Ratner N, Brady ST: Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility. EMBO J 2002, 21(3):281-293.
• [112]Kochubey O, Lou X, Schneggenburger R: Regulation of transmitter release by Ca(2+) and synaptotagmin: insights from a large CNS synapse. Trends Neurosci 2011, 34(5):237-246.
• [113]Chen YA, Scheller RH: SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol 2001, 2(2):98-106.
• [114]Martens S, Kozlov MM, McMahon HT: How synaptotagmin promotes membrane fusion. Science 2007, 316(5828):1205-1208.
• [115]Vrljic M, Strop P, Ernst JA, Sutton RB, Chu S, Brunger AT: Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2 + −triggered vesicle fusion. Nat Struct Mol Biol 2010, 17(3):325-331.
• [116]Vennekate W, Schroder S, Lin CC, van den Bogaart G, Grunwald M, Jahn R, Walla PJ: Cis- and trans-membrane interactions of synaptotagmin-1. Proc Natl Acad Sci U S A 2012, 109(27):11037-11042.
• [117]Marqueze-Pouey B, Wisden W, Malosio ML, Betz H: Differential expression of synaptophysin and synaptoporin mRNAs in the postnatal rat central nervous system. J Neurosci 1991, 11(11):3388-3397.
• [118]Bergmann M, Schuster T, Grabs D, Marqueze-Pouey B, Betz H, Traurig H, Mayerhofer A, Gratzl M: Synaptophysin and synaptoporin expression in the developing rat olfactory system. Brain Res Dev Brain Res 1993, 74(2):235-244.
• [119]Brandstatter JH, Lohrke S, Morgans CW, Wassle H: Distributions of two homologous synaptic vesicle proteins, synaptoporin and synaptophysin, in the mammalian retina. J Comp Neurol 1996, 370(1):1-10.
• [120]Khaitovich P, Muetzel B, She X, Lachmann M, Hellmann I, Dietzsch J, Steigele S, Do HH, Weiss G, Enard W, Heissig F, Arendt T, Nieselt-Struwe K, Eichler EE, Pääbo S: Regional patterns of gene expression in human and chimpanzee brains. Genome Res 2004, 14(8):1462-1473.
• [121]Khaitovich P, Weiss G, Lachmann M, Hellmann I, Enard W, Muetzel B, Wirkner U, Ansorge W, Pääbo S: A neutral model of transcriptome evolution. PLoS Biol 2004, 2(5):E132.
• [122]Sandberg R, Yasuda R, Pankratz DG, Carter TA, Del Rio JA, Wodicka L, Mayford M, Lockhart DJ, Barlow C: Regional and strain-specific gene expression mapping in the adult mouse brain. Proc Natl Acad Sci U S A 2000, 97(20):11038-11043.
• [123]Dietz JA, Li Y, Chung LM, Yandell BS, Schlamp CL, Nickells RW: Rgcs1, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice. BMC Neurosci 2008, 9:74. BioMed Central Full Text
• [124]Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 2003, 4(5):3. BioMed Central Full Text
• [125]Ryan JC, Morey JS, Bottein MY, Ramsdell JS, Van Dolah FM: Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response. BMC Neurosci 2010, 11:107. BioMed Central Full Text