{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:35:19Z","timestamp":1787592919665,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T00:00:00Z","timestamp":1599782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stiftung Dr. Liselotte and Dr. Karl-Robert Brauns, Hamburg, Germany","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We have recently demonstrated that neural stem cell-based intravitreal co-administration of glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) confers profound protection to injured retinal ganglion cells (RGCs) in a mouse optic nerve crush model, resulting in the survival of ~38% RGCs two months after the nerve lesion. Here, we analyzed whether this neuroprotective effect is long-lasting and studied the impact of the pronounced RGC rescue on axonal regeneration. To this aim, we co-injected a GDNF- and a CNTF-overexpressing neural stem cell line into the vitreous cavity of adult mice one day after an optic nerve crush and determined the number of surviving RGCs 4, 6 and 8 months after the lesion. Remarkably, we found no significant decrease in the number of surviving RGCs between the successive analysis time points, indicating that the combined administration of GDNF and CNTF conferred lifelong protection to injured RGCs. While the simultaneous administration of GDNF and CNTF stimulated pronounced intraretinal axon growth when compared to retinas treated with either factor alone, numbers of regenerating axons in the distal optic nerve stumps were similar in animals co-treated with both factors and animals treated with CNTF only.<\/jats:p>","DOI":"10.3390\/cells9092082","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T09:05:16Z","timestamp":1599815116000},"page":"2082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Intravitreal Co-Administration of GDNF and CNTF Confers Synergistic and Long-Lasting Protection against Injury-Induced Cell Death of Retinal Ganglion Cells in Mice"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6893-9714","authenticated-orcid":false,"given":"Simon","family":"Dulz","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Bassal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Flachsbarth","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9050-6766","authenticated-orcid":false,"given":"Kristoffer","family":"Riecken","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-7211","authenticated-orcid":false,"given":"Boris","family":"Fehse","sequence":"additional","affiliation":[{"name":"Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Schlichting","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-neuro-071714-034120","article-title":"The types of retinal ganglion cells: Current status and implications for neuronal classification","volume":"38","author":"Sanes","year":"2015","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature16468","article-title":"The functional diversity of retinal ganglion cells in the mouse","volume":"529","author":"Baden","year":"2016","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41467-018-05134-3","article-title":"Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes","volume":"9","author":"Rheaume","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1002\/cne.23635","article-title":"Retinofugal projections in the mouse","volume":"522","author":"Morin","year":"2014","journal-title":"J. Comp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.preteyeres.2018.11.006","article-title":"Return of function after CNS axon regeneration: Lessons from injury-responsive intrinsically photosensitive and alpha retinal ganglion cells","volume":"71","author":"Berry","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.neuroscience.2014.11.002","article-title":"The injury resistant ability of melanopsin-expressing intrinsically photosensitive retinal ganglion cells","volume":"284","author":"Cui","year":"2015","journal-title":"Neuroscience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.exer.2016.06.006","article-title":"Who\u2019s lost first? Susceptibility of retinal ganglion cell types in experimental glaucoma","volume":"158","author":"Ou","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(10)61423-7","article-title":"Glaucoma","volume":"377","author":"Quigley","year":"2011","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1515\/revneuro-2013-0003","article-title":"Optic neuropathies: Characteristic features and mechanisms of retinal ganglion cell loss","volume":"24","author":"You","year":"2013","journal-title":"Rev. Neurosci."},{"key":"ref_10","first-page":"107","article-title":"Glaucoma -state of the art and perspectives on treatment","volume":"34","author":"Skup","year":"2015","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s41433-018-0050-2","article-title":"Neuroprotective agents in the management of glaucoma","volume":"32","author":"Nucci","year":"2018","journal-title":"Eye"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.stem.2018.05.013","article-title":"Regenerating Eye Tissues to Preserve and Restore Vision","volume":"22","author":"Stern","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1002\/dvdy.24672","article-title":"Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead","volume":"248","author":"Miltner","year":"2019","journal-title":"Dev. Dyn."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3389\/fnins.2018.00651","article-title":"Pluripotent Stem Cell-Based Approaches to Explore and Treat Optic Neuropathies","volume":"12","author":"Rabesandratana","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/gt.2011.142","article-title":"Gene therapy for retinal ganglion cell neuroprotection in glaucoma","volume":"19","author":"Wilson","year":"2012","journal-title":"Gene Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.preteyeres.2011.11.002","article-title":"The molecular basis of retinal ganglion cell death in glaucoma","volume":"31","author":"Almasieh","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-407178-0.00002-8","article-title":"Neurotrophic factors and the regeneration of adult retinal ganglion cell axons","volume":"106","author":"Harvey","year":"2012","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.nbd.2016.01.021","article-title":"Biology of GDNF and its receptors - Relevance for disorders of the central nervous system","volume":"97","author":"Ibanez","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: Signalling, biological functions and therapeutic value","volume":"3","author":"Airaksinen","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrn2054","article-title":"The neuropoietic cytokine family in development, plasticity, disease and injury","volume":"8","author":"Bauer","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1038\/sj.gt.3302791","article-title":"AAV-mediated expression of CNTF promotes long-term survival and regeneration of adult rat retinal ganglion cells","volume":"13","author":"Leaver","year":"2006","journal-title":"Gene Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1089\/neu.2011.1928","article-title":"Post-injury delivery of rAAV2-CNTF combined with short-term pharmacotherapy is neuroprotective and promotes extensive axonal regeneration after optic nerve trauma","volume":"28","author":"Hellstrom","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7029","DOI":"10.1167\/iovs.14-15266","article-title":"Neural stem cell-based intraocular administration of ciliary neurotrophic factor attenuates the loss of axotomized ganglion cells in adult mice","volume":"55","author":"Flachsbarth","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.nbd.2012.11.011","article-title":"Long-distance axonal regeneration induced by CNTF gene transfer is impaired by axonal misguidance in the injured adult optic nerve","volume":"51","author":"Pernet","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7544","DOI":"10.1167\/iovs.13-13045","article-title":"Intravitreally transplanted dental pulp stem cells promote neuroprotection and axon regeneration of retinal ganglion cells after optic nerve injury","volume":"54","author":"Mead","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF02284793","article-title":"Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve","volume":"25","author":"Berry","year":"1996","journal-title":"J. Neurocytol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1073\/pnas.87.5.1855","article-title":"Schwann cells promote the survival of rat retinal ganglion cells after optic nerve section","volume":"87","author":"Maffei","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1167\/iovs.09-4509","article-title":"Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma","volume":"51","author":"Johnson","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jcyt.2015.12.002","article-title":"Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma","volume":"18","author":"Mead","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3727\/096368910X492625","article-title":"Death of axotomized retinal ganglion cells delayed after intraoptic nerve transplantation of olfactory ensheathing cells in adult rats","volume":"19","author":"Wu","year":"2010","journal-title":"Cell Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8397521","DOI":"10.1155\/2019\/8397521","article-title":"Therapeutic Strategies for Attenuation of Retinal Ganglion Cell Injury in Optic Neuropathies: Concepts in Translational Research and Therapeutic Implications","volume":"2019","author":"Fu","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.survophthal.2014.07.001","article-title":"Stem cell therapy for glaucoma: Science or snake oil?","volume":"60","author":"Sun","year":"2015","journal-title":"Surv. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/(SICI)1097-4695(19990215)38:3<382::AID-NEU7>3.0.CO;2-5","article-title":"Glial cell line-derived neurotrophic factor (GDNF) promotes the survival of axotomized retinal ganglion cells in adult rats: Comparison to and combination with brain-derived neurotrophic factor (BDNF)","volume":"38","author":"Yan","year":"1999","journal-title":"J. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S0306-4522(01)00557-7","article-title":"Neurturin enhances the survival of axotomized retinal ganglion cells in vivo: Combined effects with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor","volume":"110","author":"Koeberle","year":"2002","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/brain\/awh706","article-title":"Neurotrophic factor synergy is required for neuronal survival and disinhibited axon regeneration after CNS injury","volume":"129","author":"Logan","year":"2006","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.exer.2018.09.006","article-title":"Pronounced synergistic neuroprotective effect of GDNF and CNTF on axotomized retinal ganglion cells in the adult mouse","volume":"176","author":"Flachsbarth","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.5966\/sctm.2013-0013","article-title":"Genetically modified neural stem cells for a local and sustained delivery of neuroprotective factors to the dystrophic mouse retina","volume":"2","author":"Jung","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/mt.2008.6","article-title":"A multicolor panel of novel lentiviral \u201cgene ontology\u201d (LeGO) vectors for functional gene analysis","volume":"16","author":"Weber","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/gt.2009.149","article-title":"Lentiviral gene ontology (LeGO) vectors equipped with novel drug-selectable fluorescent proteins: New building blocks for cell marking and multi-gene analysis","volume":"17","author":"Weber","year":"2010","journal-title":"Gene Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/0896-6273(95)90015-2","article-title":"Lack of evidence that myelin-associated glycoprotein is a major inhibitor of axonal regeneration in the CNS","volume":"15","author":"Bartsch","year":"1995","journal-title":"Neuron"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1460-9568.1992.tb00881.x","article-title":"Immunohistological Localization of Tenascin in the Developing and Lesioned Adult Mouse Optic Nerve","volume":"4","author":"Bartsch","year":"1992","journal-title":"Eur. J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jankowiak, W., Kruszewski, K., Flachsbarth, K., Skevas, C., Richard, G., Ruther, K., Braulke, T., and Bartsch, U. (2015). Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127204"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Conti, L., Pollard, S.M., Gorba, T., Reitano, E., Toselli, M., Biella, G., Sun, Y., Sanzone, S., Ying, Q.L., and Cattaneo, E. (2005). Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030283"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"i112","DOI":"10.1093\/cercor\/bhj167","article-title":"Adherent neural stem (NS) cells from fetal and adult forebrain","volume":"16","author":"Pollard","year":"2006","journal-title":"Cereb. Cortex"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Glaser, T., Pollard, S.M., Smith, A., and Brustle, O. (2007). Tripotential differentiation of adherently expandable neural stem (NS) cells. PLoS ONE, 2.","DOI":"10.1371\/journal.pone.0000298"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1101\/gad.995802","article-title":"Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1\/eIF4E","volume":"16","author":"Fingar","year":"2002","journal-title":"Genes Dev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.08.053","article-title":"The regulation of cell size","volume":"154","author":"Lloyd","year":"2013","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5416","DOI":"10.1038\/ncomms6416","article-title":"The mTORC1 effectors S6K1 and 4E-BP play different roles in CNS axon regeneration","volume":"5","author":"Yang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/glia.21155","article-title":"GDNF-induced osteopontin from Muller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration","volume":"59","author":"Irmler","year":"2011","journal-title":"Glia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/mt.2016.102","article-title":"Boosting Central Nervous System Axon Regeneration by Circumventing Limitations of Natural Cytokine Signaling","volume":"24","author":"Leibinger","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/nbdi.2002.0543","article-title":"Potential synergistic protection of retinal ganglion cells from axotomy-induced apoptosis by adenoviral administration of glial cell line-derived neurotrophic factor and X-chromosome-linked inhibitor of apoptosis","volume":"11","author":"Straten","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1046\/j.1460-9568.2002.01893.x","article-title":"Dose-dependent rescue of axotomized rat retinal ganglion cells by adenovirus-mediated expression of glial cell-line derived neurotrophic factor in vivo","volume":"15","author":"Schmeer","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"116","DOI":"10.2174\/156652311794940746","article-title":"Retinal ganglion cell gene therapy and visual system repair","volume":"11","author":"Hellstrom","year":"2011","journal-title":"Curr. Gene Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1038\/mt.2015.68","article-title":"CNTF Gene Therapy Confers Lifelong Neuroprotection in a Mouse Model of Human Retinitis Pigmentosa","volume":"23","author":"Lipinski","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1167\/iovs.10-6479","article-title":"Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment","volume":"52","author":"Talcott","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1046\/j.1471-4159.1997.68030979.x","article-title":"Evidence for multiple, local functions of ciliary neurotrophic factor (CNTF) in retinal development: Expression of CNTF and its receptors and in vitro effects on target cells","volume":"68","author":"Kirsch","year":"1997","journal-title":"J. Neurochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/cne.21174","article-title":"Immunohistochemical localization of CNTFR\u03b1 in adult mouse retina and optic nerve following intraorbital nerve crush: Evidence for the axonal loss of a trophic factor receptor after injury","volume":"500","author":"Miotke","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_58","first-page":"715","article-title":"Expression of cytokine signal transduction components in the postnatal mouse retina","volume":"9","author":"Rhee","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.expneurol.2004.02.002","article-title":"GDNF, Ret, GFRalpha1 and 2 in the adult rat retino-tectal system after optic nerve transection","volume":"187","author":"Lindqvist","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0306-4522(03)00599-2","article-title":"Potential role of glial cell line-derived neurotrophic factor receptors in Muller glial cells during light-induced retinal degeneration","volume":"122","author":"Harada","year":"2003","journal-title":"Neuroscience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"E4520","DOI":"10.1073\/pnas.1303604110","article-title":"CNTF-mediated protection of photoreceptors requires initial activation of the cytokine receptor gp130 in M\u00fcller glial cells","volume":"110","author":"Rhee","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1128\/MCB.26.7.2746-2757.2006","article-title":"GDNF family ligands trigger indirect neuroprotective signaling in retinal glial cells","volume":"26","author":"Hauck","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/sj.cdd.4402281","article-title":"The upregulation of GLAST-1 is an indirect antiapoptotic mechanism of GDNF and neurturin in the adult CNS","volume":"15","author":"Koeberle","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/neu.20117","article-title":"Ciliary neurotrophic factor protects retinal ganglion cells from axotomy-induced apoptosis via modulation of retinal glia in vivo","volume":"63","author":"Arnold","year":"2005","journal-title":"J. Neurobiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/jnr.23449","article-title":"Artemin augments survival and axon regeneration in axotomized retinal ganglion cells","volume":"92","author":"Omodaka","year":"2014","journal-title":"J. Neurosci. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.expneurol.2013.03.001","article-title":"Three-dimensional evaluation of retinal ganglion cell axon regeneration and pathfinding in whole mouse tissue after injury","volume":"247","author":"Luo","year":"2013","journal-title":"Exp. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.tins.2014.05.002","article-title":"Lost in the jungle: New hurdles for optic nerve axon regeneration","volume":"37","author":"Pernet","year":"2014","journal-title":"Trends Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3389\/fncel.2020.00119","article-title":"Strategies to Promote Long-Distance Optic Nerve Regeneration","volume":"14","author":"Yang","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_69","first-page":"525","article-title":"Optic nerve regeneration: A long view","volume":"37","author":"Yin","year":"2019","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.neuron.2015.02.017","article-title":"Subtype-specific regeneration of retinal ganglion cells following axotomy: Effects of osteopontin and mTOR signaling","volume":"85","author":"Duan","year":"2015","journal-title":"Neuron"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1126\/science.aal5060","article-title":"Regenerating optic pathways from the eye to the brain","volume":"356","author":"Laha","year":"2017","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.expneurol.2015.12.015","article-title":"Reaching the brain: Advances in optic nerve regeneration","volume":"287","author":"Benowitz","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1073\/pnas.91.5.1632","article-title":"Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells","volume":"91","author":"Clarke","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.brainres.2004.09.038","article-title":"Intravitreal transplants of Schwann cells and fibroblasts promote the survival of axotomized retinal ganglion cells in rats","volume":"1029","author":"Li","year":"2004","journal-title":"Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bray, E.R., Noga, M., Thakor, K., Wang, Y., Lemmon, V.P., Park, K.K., and Tsoulfas, P. (2017). 3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths. eNeuro, 4.","DOI":"10.1523\/ENEURO.0093-17.2017"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7484","DOI":"10.1167\/iovs.12-9970","article-title":"Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases","volume":"53","author":"Kauper","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6241","DOI":"10.1073\/pnas.1018987108","article-title":"Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration","volume":"108","author":"Zhang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ophtha.2018.09.041","article-title":"Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial","volume":"126","author":"Chew","year":"2019","journal-title":"Ophthalmology"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/9\/2082\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:09:07Z","timestamp":1760177347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/9\/2082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,11]]},"references-count":78,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["cells9092082"],"URL":"https:\/\/doi.org\/10.3390\/cells9092082","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,11]]}}}