{"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":1787592919626,"version":"build-2736575974"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rudolf und Anna Katharina Eichenauer foundation","award":["201906170065"],"award-info":[{"award-number":["201906170065"]}]},{"name":"China Scholarship Council","award":["201906170065"],"award-info":[{"award-number":["201906170065"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>We recently showed, in a mouse optic nerve crush model, that a sustained cell-based intravitreal administration of ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) synergistically slowed the lesion-induced degeneration of retinal ganglion cells (RGCs), resulting in the presence of approximately 35% viable RGCs eight months after the lesion. However, the combinatorial neuroprotective treatment was initiated shortly after the lesion. To mimic a more clinically relevant situation, we co-administered both factors either three or five days after an intraorbital nerve crush when approximately 35% or 57% of the RGCs were degenerated, respectively. Analyses of the retinas at different time points after the lesion consistently revealed the presence of significantly more surviving RGCs in retinas co-treated with CNTF and GDNF than in retinas treated with either factor alone. For example, when the neurotrophic factors were administered five days after the nerve crush and the animals were analyzed two months after the lesion, retinas co-treated with CNTF and GDNF contained approximately 40% of the RGCs present at the start of treatment. In comparison, monotherapy with either CNTF or GDNF protected only about 15% or 10% of the RGCs present at baseline, respectively. The number of regenerating axons in the distal nerve stumps was similar in CNTF- and CNTF\/GDNF-treated animals, despite the significantly higher number of rescued RGCs in the latter group. These findings have potential implications for studies aimed at developing neuroprotective treatments for optic neuropathies such as glaucoma.<\/jats:p>","DOI":"10.3390\/cells14090643","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:35:13Z","timestamp":1746185713000},"page":"643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Survival and Axonal Regeneration of Retinal Ganglion Cells in a Mouse Optic Nerve Crush Model After a Cell-Based Intravitreal Co-Administration of Ciliary Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor at Different Post-Lesion Time Points"],"prefix":"10.3390","volume":"14","author":[{"given":"Yue","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn Michelle","family":"Grodzki","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\/0000-0003-3227-7568","authenticated-orcid":false,"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":[[2025,4,28]]},"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":"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_3","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","article-title":"Single-Cell Profiles of Retinal Ganglion Cells Differing in Resilience to Injury Reveal Neuroprotective Genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","unstructured":"Tapia, M.L., Nascimento-Dos-Santos, G., and Park, K.K. (2022). Subtype-specific survival and regeneration of retinal ganglion cells in response to injury. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.956279"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.neuron.2019.05.044","article-title":"Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells","volume":"103","author":"Bray","year":"2019","journal-title":"Neuron"},{"key":"ref_7","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_8","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_9","doi-asserted-by":"crossref","first-page":"R139","DOI":"10.1093\/hmg\/ddx273","article-title":"Optic neuropathies: The tip of the neurodegeneration iceberg","volume":"26","author":"Carelli","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1350-9462(02)00012-5","article-title":"Retinal ganglion cell disorders: Types and treatments","volume":"21","author":"Levin","year":"2002","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Albarral, J.A., Ram\u00edrez, A.I., de Hoz, R., Matamoros, J.A., Salobrar-Garc\u00eda, E., Elvira-Hurtado, L., L\u00f3pez-Cuenca, I., S\u00e1nchez-Puebla, L., Salazar, J.J., and Ram\u00edrez, J.M. (2024). Glaucoma: From pathogenic mechanisms to retinal glial cell response to damage. Front. Cell Neurosci., 18.","DOI":"10.3389\/fncel.2024.1354569"},{"key":"ref_16","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_17","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_18","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1159\/000514441","article-title":"Neuroprotective factors of the retina and their role in promoting survival of retinal ganglion cells: A review","volume":"64","author":"Fudalej","year":"2021","journal-title":"Ophthalmic Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108506","DOI":"10.1016\/j.exer.2021.108506","article-title":"Protection of retinal ganglion cells in glaucoma: Current status and future","volume":"205","author":"Shen","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_20","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_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":"2194","DOI":"10.1167\/iovs.08-3013","article-title":"Effect of CNTF on retinal ganglion cell survival in experimental glaucoma","volume":"50","author":"Pease","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.exer.2009.02.015","article-title":"Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: A quantitative in vivo study","volume":"89","author":"Agudo","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/0006-8993(93)90695-J","article-title":"Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo","volume":"602","author":"Mey","year":"1993","journal-title":"Brain Res."},{"key":"ref_25","first-page":"1783","article-title":"Intravitreal injections of GDNF-loaded biodegradable microspheres are neuroprotective in a rat model of glaucoma","volume":"13","author":"Jiang","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1097\/00001756-199711100-00005","article-title":"In vivo neurotrophic effects of GDNF on axotomized retinal ganglion cells","volume":"8","author":"Isenmann","year":"1997","journal-title":"Neuroreport"},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1016\/S0042-6989(97)00364-7","article-title":"Effects of GDNF on retinal ganglion cell survival following axotomy","volume":"38","author":"Koeberle","year":"1998","journal-title":"Vision Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/jps.20629","article-title":"Neuroprotection of retinal ganglion cells in DBA\/2J mice with GDNF-loaded biodegradable microspheres","volume":"96","author":"Ward","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_30","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_31","doi-asserted-by":"crossref","unstructured":"Dulz, S., Bassal, M., Flachsbarth, K., Riecken, K., Fehse, B., Schlichting, S., Bartsch, S., and Bartsch, U. (2020). Intravitreal Co-Administration of GDNF and CNTF Confers Synergistic and Long-Lasting Protection against Injury-Induced Cell Death of Retinal Ganglion Cells in Mice. Cells, 9.","DOI":"10.3390\/cells9092082"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.neuroscience.2016.12.027","article-title":"AAV-mediated transfer of RhoA shRNA and CNTF promotes retinal ganglion cell survival and axon regeneration","volume":"343","author":"Cen","year":"2017","journal-title":"Neuroscience"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.nbd.2016.01.021","article-title":"Biology of GDNF and its receptors\u2014Relevance for disorders of the central nervous system","volume":"97","author":"Ibanez","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.tins.2008.05.003","article-title":"GDNF and GFRalpha: A versatile molecular complex for developing neurons","volume":"31","author":"Paratcha","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00441-020-03287-6","article-title":"GDNF synthesis, signaling, and retrograde transport in motor neurons","volume":"382","author":"Boynton","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mahato, A.K., and Sidorova, Y.A. (2020). RET Receptor Tyrosine Kinase: Role in Neurodegeneration, Obesity, and Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197108"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"Heinrich","year":"2003","journal-title":"Biochem. J."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","unstructured":"Rose-John, S. (2018). Interleukin-6 Family Cytokines. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a028415"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cytogfr.2015.07.007","article-title":"Ciliary neurotrophic factor (CNTF): New facets of an old molecule for treating neurodegenerative and metabolic syndrome pathologies","volume":"26","author":"Pasquin","year":"2015","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41577-018-0066-7","article-title":"Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer","volume":"18","author":"Jones","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2019.03.027","article-title":"Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines","volume":"50","author":"Murakami","year":"2019","journal-title":"Immunity"},{"key":"ref_45","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_46","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_47","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_48","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_49","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/0896-6273(95)90172-8","article-title":"Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture","volume":"15","author":"Kaplan","year":"1995","journal-title":"Neuron"},{"key":"ref_50","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_51","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_52","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","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_54","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_55","doi-asserted-by":"crossref","unstructured":"Duda, S., Block, C.T., Pradhan, D.R., Arzhangnia, Y., Klaiber, A., Greschner, M., and Puller, C. (2025). Spatial distribution and functional integration of displaced retinal ganglion cells. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-91045-5"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.cub.2013.12.020","article-title":"Visual space is represented by nonmatching topographies of distinct mouse retinal ganglion cell types","volume":"24","author":"Bleckert","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-vision-121219-081831","article-title":"Topographic Variations in Retinal Encoding of Visual Space","volume":"6","author":"Heukamp","year":"2020","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0012-1606(87)90038-8","article-title":"Anterograde tracing of retinal axons in the avian embryo with low molecular weight derivatives of biotin","volume":"119","author":"Halfter","year":"1987","journal-title":"Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jankowiak, W., Kruszewski, K., Flachsbarth, K., Skevas, C., Richard, G., R\u00fcther, 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_60","doi-asserted-by":"crossref","unstructured":"Hu, Y., Grodzki, L.M., Bartsch, S., and Bartsch, U. (2021). Cell-Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies. Biology, 10.","DOI":"10.3390\/biology10111181"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Boia, R., Ruzafa, N., Aires, I.D., Pereiro, X., Ambrosio, A.F., Vecino, E., and Santiago, A.R. (2020). Neuroprotective Strategies for Retinal Ganglion Cell Degeneration: Current Status and Challenges Ahead. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072262"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/tvst.10.9.6","article-title":"Retinal Protection by Sustained Nanoparticle Delivery of Oncostatin M and Ciliary Neurotrophic Factor Into Rodent Models of Retinal Degeneration","volume":"10","author":"Yang","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wojcik-Gryciuk, A., Gajewska-Wozniak, O., Kordecka, K., Boguszewski, P.M., Waleszczyk, W., and Skup, M. (2020). Neuroprotection of Retinal Ganglion Cells with AAV2-BDNF Pretreatment Restoring Normal TrkB Receptor Protein Levels in Glaucoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176262"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/sj.gt.3302277","article-title":"Effect of GDNF gene transfer into axotomized retinal ganglion cells using in vivo electroporation with a contact lens-type electrode","volume":"12","author":"Ishikawa","year":"2005","journal-title":"Gene Ther."},{"key":"ref_65","first-page":"741","article-title":"Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons","volume":"41","author":"Quigley","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1001\/archopht.124.6.853","article-title":"Visual field defects and retinal ganglion cell losses in patients with glaucoma","volume":"124","author":"Harwerth","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1016\/j.neuron.2022.06.002","article-title":"Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells","volume":"110","author":"Jacobi","year":"2022","journal-title":"Neuron"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.exer.2011.02.008","article-title":"Axotomy-induced retinal ganglion cell death in adult mice: Quantitative and topographic time course analyses","volume":"92","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1167\/iovs.15-17841","article-title":"Apoptotic Retinal Ganglion Cell Death After Optic Nerve Transection or Crush in Mice: Delayed RGC Loss With BDNF or a Caspase 3 Inhibitor","volume":"57","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Itkonen, J., Annala, A., Tavakoli, S., Arango-Gonzalez, B., Ueffing, M., Toropainen, E., Ruponen, M., Casteleijn, M.G., and Urtti, A. (2020). Characterization, Stability, and in Vivo Efficacy Studies of Recombinant Human CNTF and Its Permeation into the Neural Retina in ex Vivo Organotypic Retinal Explant Culture Models. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070611"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.exer.2010.09.016","article-title":"Pharmacokinetics of intravitreal glial cell line-derived neurotrophic factor: Experimental studies in pigs","volume":"91","author":"Ejstrup","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_72","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_73","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_74","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_75","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.brainres.2004.03.030","article-title":"Ciliary neurotrophic factor and its receptors are differentially expressed in the optic nerve transected adult rat retina","volume":"1013","author":"Sarup","year":"2004","journal-title":"Brain Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.mcn.2009.03.002","article-title":"Exogenous CNTF stimulates axon regeneration of retinal ganglion cells partially via endogenous CNTF","volume":"41","author":"Hauk","year":"2009","journal-title":"Mol. Cell Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/glia.21155","article-title":"GDNF-induced osteopontin from M\u00fcller glial cells promotes photoreceptor survival in the Pde6brd1 mouse model of retinal degeneration","volume":"59","author":"Irmler","year":"2011","journal-title":"Glia"},{"key":"ref_78","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_79","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1523\/JNEUROSCI.22-21-09228.2002","article-title":"Microglia-M\u00fcller glia cell interactions control neurotrophic factor production during light-induced retinal degeneration","volume":"22","author":"Harada","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_80","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 M\u00fcller glial cells during light-induced retinal degeneration","volume":"122","author":"Harada","year":"2003","journal-title":"Neuroscience"},{"key":"ref_81","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_82","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_83","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_84","doi-asserted-by":"crossref","first-page":"e734","DOI":"10.1038\/cddis.2013.266","article-title":"Misguidance and modulation of axonal regeneration by Stat3 and Rho\/ROCK signaling in the transparent optic nerve","volume":"4","author":"Pernet","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1167\/iovs.16-19873","article-title":"Regenerative Responses and Axon Pathfinding of Retinal Ganglion Cells in Chronically Injured Mice","volume":"58","author":"Yungher","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1016\/j.visres.2004.06.010","article-title":"Axotomized mouse retinal ganglion cells containing melanopsin show enhanced survival, but not enhanced axon regrowth into a peripheral nerve graft","volume":"44","author":"Robinson","year":"2004","journal-title":"Vision. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6095","DOI":"10.1167\/iovs.15-17195","article-title":"Long-Term Effect of Optic Nerve Axotomy on the Retinal Ganglion Cell Layer","volume":"56","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Perez de Sevilla Muller, L., Sargoy, A., Rodriguez, A.R., and Brecha, N.C. (2014). Melanopsin ganglion cells are the most resistant retinal ganglion cell type to axonal injury in the rat retina. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093274"},{"key":"ref_90","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1073\/pnas.0600236103","article-title":"Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants","volume":"103","author":"Sieving","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ajo.2013.03.021","article-title":"Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa","volume":"156","author":"Birch","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_93","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_94","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_95","doi-asserted-by":"crossref","first-page":"6301","DOI":"10.1167\/iovs.14-14860","article-title":"CNGB3-achromatopsia clinical trial with CNTF: Diminished rod pathway responses with no evidence of improvement in cone function","volume":"55","author":"Zein","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"13523","DOI":"10.1523\/JNEUROSCI.4021-06.2006","article-title":"Regulation of rod phototransduction machinery by ciliary neurotrophic factor","volume":"26","author":"Wen","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1167\/iovs.06-0677","article-title":"Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa","volume":"48","author":"Rhee","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Wang, Y., Rhee, K.D., Pellegrini, M., and Yang, X.J. (2020). Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63519-1"},{"key":"ref_99","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_100","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"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"100298","DOI":"10.1016\/j.xops.2023.100298","article-title":"Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma: Safety, Neuroprotection, and Neuroenhancement","volume":"3","author":"Goldberg","year":"2023","journal-title":"Ophthalmol. Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/9\/643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:23:09Z","timestamp":1760030589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/9\/643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":101,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["cells14090643"],"URL":"https:\/\/doi.org\/10.3390\/cells14090643","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]}}}