Home > Archive>Volume 10, Issue 1, 2017 >35-42. DOI:10.18240/ijo.2017.01.06
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Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice
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Xiao-Ming Chen. Department of Ophthalmology, West China Hospital, Chengdu 600041, Sichuan Province, China. chenxm58@163.com. Ting-Hua Wang; Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. tinghua_neuron @263.net

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Supported by the National Major Scientific Equipment program (No.2012YQ12008005); the Institute of Neurological Disease, West China Hospital, Sichuan University.

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    Abstract:

    AIM: To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS: C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS: The density (cell number/mm2) of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control (P<0.05). RGCs in BMSCs treated eyes was 625.07±89.64/mm2, significantly higher than that of no or PBS treatment (P<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07+39.77) and GIM (326.67+33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION: Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs.

    Reference
    1 Furtado JM, Lansingh VC, Carter MJ, Milanese MF, Peña BN, Ghersi HA, Bote PL, Nano ME, Silva JC. Causes of blindness and visual impairment in Latin America. Surv Ophthalmol 2012;57(2):149-177.
    2 Pirouzmand F. Epidemiological trends of traumatic optic nerve injuries in the largest Canadian adult trauma center. J Craniofac Surg 2012;23(2):516-520.
    3 Lagrèze W. Treatment of optic neuropathies-state of the art. Klin Monbl Augenheilkd 2009;226(11):875-880.
    4 Selhorst JB, Chen Y. The optic nerve. Semin Neurol 2009;29(1):29-35.
    5 Richardson PM, McGuinness UM, Aguayo AJ. Axons from CNS neurons regenerate into PNS grafts. Nature 1980;284(5753):264-265.
    6 Murphy JA, Clarke DB. Target-derived neurotrophins may influence the survival of adult retinal ganglion cells when local neurotrophic support is disrupted: implications for glaucoma. Med Hypotheses 2006;67(5):1208-1212.
    7 Iwabe S, Moreno-Mendoza NA, Trigo-Tavera F, Crowder C, García-Sánchez GA. Retrograde axonal transport obstruction of brain-derived neurotrophic factor (BDNF) and its TrkB receptor in the retina and optic nerve of American Cocker Spaniel dogs with spontaneous glaucoma. Vet Ophthalmol 2007;10(Suppl 1):12-19.
    8 Ma YT, Hsieh T, Forbes ME, Johnson JE, Frost DO. BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death. J Neurosci 1998;18(6):2097-2107.
    9 Rohrer B, LaVail MM, Jones KR, Reichardt LF. Neurotrophin receptor TrkB activation is not required for the postnatal survival of retinal ganglion cells in vivo. Exp Neurol 2001;172(1):81-91.
    10 Chen H, Weber AJ. BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci 2001;42(5):966-974.
    11 Parrilla-Reverter G, Agudo M, Sobrado-Calvo P, Salinas-Navarro M, Villegas-Pérez MP, Vidal-Sanz M. Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study. Exp Eye Res 2009;89(1):32-41.
    12 Jiang C, Moore MJ, Zhang X, Klassen H, Langer R, Young M. Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma. Mol Vis 2007;13:1783-1792.
    13 Bull ND, Limb GA, Martin KR. Human Müller stem cell (MIO-M1) transplantation in a rat model of glaucoma: survival, differentiation, and integration. Invest Ophthalmol Vis Sci 2008;49(8):3449-3456.
    14 Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR. Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma. Invest Ophthalmol Vis Sci 2010;51(4):2051-2059.
    15 Tomita M, Adachi Y, Yamada H, Takahashi K, Kiuchi K, Oyaizu H, Ikebukuro K, Kaneda H, Matsumura M, Ikehara S. Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina. Stem Cells 2002;20(4):279-283.
    16 Bull ND, Johnson TV, Martin KR. Stem cells for neuroprotection in glaucoma. Prog Brain Res 2008;173:511-519.
    17 Scalinci SZ, Scorolli L, Corradetti G, Domanico D, Vingolo EM, Meduri A, Bifani M, Siravo D. Potential role of intravitreal human placental stem cell implants in inhibiting progression of diabetic retinopathy in type 2 diabetes: neuroprotective growth factors in the vitreous. Clin Ophthalmol 2011;5:691-696.
    18 Mead B, Logan A, Berry M, Leadbeater W, Scheven BA. Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury. Invest Ophthalmol Vis Sci 2013;54(12):7544-7556.
    19 Johnson TV, DeKorver NW, Levasseur VA, Osborne A, Tassoni A, Lorber B, Heller JP, Villasmil R, Bull ND, Martin KR, Tomarev SI. Identification of retinal ganglion cell neuroprotection conferred by platelet-derived growth factor through analysis of the mesenchymal stem cell secretome. Brain 2014;137(Pt 2):503-519.
    20 Yu S, Tanabe T, Dezawa M, Ishikawa H, Yoshimura N. Effects of bone marrow stromal cell injection in an experimental glaucoma model. Biochem Biophys Res Commun 2006;344(4):1071-1079.
    21 Zwart I, Hill AJ, Al-Allaf F, Shah M, Girdlestone J, Sanusi AB, Mehmet H, Navarrete R, Navarrete C, Jen LS. Umbilical cord blood mesenchymal stromal cells are neuroprotective and promote regeneration in a rat optic tract model. Exp Neurol 2009;216(2):439-448.
    22 Mesentier-Louro LA, Zaverucha-do-Valle C, da Silva-Junior AJ, Nascimento-Dos-Santos G, Gubert F, de Figueirêdo AB, Torres AL, Paredes BD, Teixeira C, Tovar-Moll F, Mendez-Otero R, Santiago MF. Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy. PLoS One 2014;9(10):e110722.
    23 Park HY, Kim JH, Sun Kim H, Park CK. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina. Brain Res 2012;1469:10-23.
    24 Levkovitch-Verbin H, Sadan O, Vander S, Rosner M, Barhum Y, Melamed E, Offen D, Melamed S. Intravitreal injections of neurotrophic factors secreting mesenchymal stem cells are neuroprotective in rat eyes following optic nerve transection. Invest Ophthalmol Vis Sci 2010;51(12):6394-6400.
    25 Harper MM, Grozdanic SD, Blits B, Kuehn MH, Zamzow D, Buss JE, Kardon RH, Sakaguchi DS. Transplantation of BDNF-secreting mesenchymal stem cells provides neuroprotection in chronically hypertensive rat eyes. Invest Ophthalmol Vis Sci 2011;52(7):4506-4515.
    26 Groh ME, Maitra B, Szekely E, Koc ON. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol 2005;33(8):928-934.
    27 Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002;99(10):3838-3843.
    28 Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007;110(10):3499-3506.
    29 Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 2009;4(3):206-216.
    30 Castanheira P, Torquetti L, Nehemy MB, Goes AM. Retinal incorporation and differentiation of mesenchymal stem cells intravitreally injected in the injured retina of rats. Arq Bras Oftalmol 2008;71(5):644-650.
    31 Li N, Li XR, Yuan JQ. Effects of bone-marrow mesenchymal stem cells transplanted into vitreous cavity of rat injured by ischemia/reperfusion. Graefes Arch Clin Exp Ophthalmol 2009;247(4):503-514.
    32 Templeton JP, Geisert EE. A practical approach to optic nerve crush in the mouse. Mol Vis 2012;18:2147-2152.
    33 Igura K, Okada M, Kim HW, Ashraf M. Identification of small juvenile stem cells in aged bone marrow and their therapeutic potential for repair of the ischemic heart. Am J Physiol Heart Circ Physiol 2013;305(9):H1354-1362.
    34 Hunt DP, Irvine KA, Webber DJ, Compston DA, Blakemore WF, Chandran S. Effects of direct transplantation of multipotent mesenchymal stromal/stem cells into the demyelinated spinal cord. Cell Transplant 2008;17(7):865-873.
    35 Feng DF, Chen ET, Li XY, Liu Y, Wang Y. Standardizing optic nerve crushes with an aneurysm clip. Neurol Res 2010;32(5):476-481.
    36 Blair M, Pease ME, Hammond J, Valenta D, Kielczewski J, Levkovitch-Verbin H, Quigley H. Effect of glatiramer acetate on primary and secondary degeneration of retinal ganglion cells in the rat. Invest Ophthalmol Vis Sci 2005;46(3):884-890.
    37 Harper MM, Adamson L, Blits B, Bunge MB, Grozdanic SD, Sakaguchi DS. Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells. Exp Eye Res 2009;89(4):538-548.
    38 Fang IM, Yang CM, Yang CH, Chiou SH, Chen MS. Transplantation of induced pluripotent stem cells without C-Myc attenuates retinal ischemia and reperfusion injury in rats. Exp Eye Res 2013;113:49-59.
    39 Falke E, Nissanov J, Mitchell TW, Bennett DA, Trojanowski JQ, Arnold SE. Subicular dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density. Am J Pathol 2003;163(4):1615-1621.
    40 Gittins R, Harrison PJ. Neuronal density, size and shape in the human anterior cingulate cortex: a comparison of Nissl and NeuN staining. Brain Res Bull 2004;63(2):155-160.
    41 Montesano G, Belfiore M,Ripamonti M, Arena A, Lamanna J, Ferro M, Zimarino V, Ambrosi A, Malgaroli A. Effects of the Concomitant Activation of ON and OFF Retinal Ganglion Cells on the Visual Thalamus: Evidence for an Enhanced Recruitment of GABAergic Cells. Front Neural Circuits 2015;9:77.
    42 Osborne A, Aldarwesh A, Rhodes JD, Broadway DC, Everitt C, Sanderson J. Hydrostatic pressure does not cause detectable changes in survival of human retinal ganglion cells. PLoS One 2015;10(1):e0115591.
    43 Kim SJ, Yoo WS, Choi M, Chung I, Yoo JM, Choi WS. Increased O-GlcNAcylation of NF-κB Enhances Retinal Ganglion Cell Death in Streptozotocin-induced Diabetic Retinopathy. Curr Eye Res 2016;41(2):249-257.
    44 Osborne A, Hopes M, Wright P, Broadway DC, Sanderson J. Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration. Exp Eye Res 2016;143:28-38.
    45 Buckingham BP, Inman DM, Lambert W, Oglesby E, Calkins DJ, Steele MR, Vetter ML, Marsh-Armstrong N, Horner PJ. Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma. J Neurosci 2008;28(11):2735-2744.
    46 Niyadurupola N, Sidaway P, Osborne A, Broadway DC, Sanderson J. The development of human organotypic retinal cultures (HORCs) to study retinal neurodegeneration. Br J Ophthalmol 2001;95(5):720-726.
    47 Grove JE, Bruscia E, Krause DS. Plasticity of bone marrow-derived stem cells. Stem Cells 2004;22(4):487-500.
    48 García R, Aguiar J, Alberti E, de la Cuétara K, Pavón N. Bone marrow stromal cells produce nerve growth factor and glial cell line-derived neurotrophic factors. Biochem Biophys Res Commun 2004;316(3):753-754.
    49 Taylor L, Arnér K, Engelsberg K, Ghosh F. Effects of glial cell line-derived neurotrophic factor on the cultured adult full-thickness porcine retina. Curr Eye Res 2013;38(4):503-515.
    50 Weber AJ, Harman CD. BDNF treatment and extended recovery from optic nerve trauma in the cat. Invest Ophthalmol Vis Sci 2013;54(10):6594-6604.
    51 Weber AJ, Harman CD. BDNF preserves the dendritic morphology of alpha and beta ganglion cells in the cat retina after optic nerve injury. Invest Ophthalmol Vis Sci 2008;49(6):2456-2463.
    52 Cellerino A, Carroll P, Thoenen H, Barde YA. Reduced size of retinal ganglion cell axons and hypomyelination in mice lacking brain-derived neurotrophic factor. Mol Cell Neurosci 1997;9(5-6):397-408.
    53 Zhao T, Li Y, Tang L, Li Y, Fan F, Jiang B. Protective effects of human umbilical cord blood stem cell intravitreal transplantation against optic nerve injury in rats. Graefes Arch Clin Exp Ophthalmol 2011;249(7):1021-1028.
    54 Deng L, Mei ZQ, Chang NB, Gao XQ, Yang CX. Effects of transplantation of bone marrow stromal cells modified by GDNF gene on BDNF and its receptor in rats following intracerebral hemorrhage. Journal of Luzhou Medical College 2012;35(5):451-454.
    55 Peng C, Aron L, Klein R, Li M, Wurst W, Prakash N, Le W. Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal dopaminergic neurons. J Neurosci 2011;31(36):12802-12815.
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Zong-Li Hu, Ni Li, Xin Wei,/et al.Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice. Int J Ophthalmol, 2017,10(1):35-42

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Publication History
  • Received:April 21,2016
  • Revised:September 04,2016
  • Online: January 04,2017
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