{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:36Z","timestamp":1787028576736,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371049"],"award-info":[{"award-number":["82371049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Optic nerve (ON) injury by trauma induces progressive retinal ganglion cell (RGC) death and axonal loss, which leads to irreversible visual impairment and even blindness. Recently, we discovered that cellular senescence is involved in RGC survival regulation post-ON injury, and senolytic (dasatinib and quercetin) treatments can promote RGC survival and electroretinography activity. Here, we aimed to further evaluate the effects of dasatinib and quercetin on RGC dendrites and axons in mice with an ON crush injury. Longitudinal in vivo imaging analysis demonstrated that the RGC dendritic shrinkage was significantly reduced in mice with both individual and combined treatment of dasatinib and quercetin as compared to the vehicle treatment group. Similarly, dasatinib and quercetin treatments significantly promoted axonal regeneration post-ON injury as compared to the vehicle-treated mice. RNA sequencing analysis showed that the differentially expressed genes were enriched in the response to glucocorticoid, calcium ion binding, and cerebral cortex development. Sybr green PCR and immunofluorescence analyses validated that the axonal extension-related gene, meteorin (Metrn), was significantly upregulated in the dasatinib-only and combined dasatinib and quercetin treatments. In summary, this study revealed that dasatinib and quercetin alleviated RGC dendritic shrinkage and promoted axonal regeneration in mice after ON injury, probably mediated through meteorin, suggesting the dendrite repair and axonal regeneration potentials of dasatinib and quercetin for traumatic optic neuropathy treatment.<\/jats:p>","DOI":"10.3390\/ijms262412170","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:45:07Z","timestamp":1766065507000},"page":"12170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dasatinib and Quercetin Alleviate Retinal Ganglion Cell Dendritic Shrinkage and Promote Axonal Regeneration in Mice with Optic Nerve Injury"],"prefix":"10.3390","volume":"26","author":[{"given":"Xin","family":"Bin","sequence":"first","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowan","family":"Chen","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yao","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Cao","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunliang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-7229","authenticated-orcid":false,"given":"Tsz Kin","family":"Ng","sequence":"additional","affiliation":[{"name":"Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China"},{"name":"Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9636897221123512","DOI":"10.1177\/09636897221123512","article-title":"Diversified Treatment Options of Adult Stem Cells for Optic Neuropathies","volume":"31","author":"Tan","year":"2022","journal-title":"Cell Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1076\/opep.5.3.143.8364","article-title":"The global impact of eye injuries","volume":"5","author":"Thylefors","year":"1998","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109159","DOI":"10.1016\/j.exer.2022.109159","article-title":"Longitudinal and simultaneous profiling of 11 modes of cell death in mouse retina post-optic nerve injury","volume":"222","author":"Yao","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.1175737","article-title":"KLF family members regulate intrinsic axon regeneration ability","volume":"326","author":"Moore","year":"2009","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nature10594","article-title":"Sustained axon regeneration induced by co-deletion of PTEN and SOCS3","volume":"480","author":"Sun","year":"2011","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1038\/s41467-025-58303-6","article-title":"Non-muscle myosin II inhibition at the site of axon injury increases axon regeneration","volume":"16","author":"Heo","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e2113751119","DOI":"10.1073\/pnas.2113751119","article-title":"Monocyte-derived SDF1 supports optic nerve regeneration and alters retinal ganglion cells\u2019 response to Pten deletion","volume":"119","author":"Xie","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1002\/stem.2812","article-title":"Human Periodontal Ligament-Derived Stem Cells Promote Retinal Ganglion Cell Survival and Axon Regeneration After Optic Nerve Injury","volume":"36","author":"Cen","year":"2018","journal-title":"Stem Cells"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109333","DOI":"10.1016\/j.jnutbio.2023.109333","article-title":"Green tea extract enhances retinal ganglion cell survival and axonal regeneration in rats with optic nerve injury. Green tea extract enhances retinal ganglion cell survival and axonal regeneration in rats with optic nerve injury","volume":"117","author":"Yuan","year":"2023","journal-title":"J. Nutr. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109787","DOI":"10.1016\/j.exer.2024.109787","article-title":"Combined treatment of human mesenchymal stem cells and green tea extract on retinal ganglion cell regeneration in rats after optic nerve injury","volume":"239","author":"Yang","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13719","DOI":"10.1111\/cpr.13719","article-title":"Cellular senescence mediates retinal ganglion cell survival regulation post-optic nerve crush injury","volume":"57","author":"Yao","year":"2024","journal-title":"Cell Prolif."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13089","DOI":"10.1111\/acel.13089","article-title":"Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension","volume":"19","author":"Rocha","year":"2020","journal-title":"Aging Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100","DOI":"10.5935\/0004-2749.20150026","article-title":"Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model","volume":"78","author":"Arikan","year":"2015","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gao, F.J., Zhang, S.H., Xu, P., Yang, B.Q., Zhang, R., Cheng, Y., Zhou, X.J., Huang, W.J., Wang, M., and Chen, J.Y. (2017). Quercetin Declines Apoptosis, Ameliorates Mitochondrial Function and Improves Retinal Ganglion Cell Survival and Function in In Vivo Model of Glaucoma in Rat and Retinal Ganglion Cell Culture In Vitro. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00285"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: From transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41591-018-0092-9","article-title":"Senolytics improve physical function and increase lifespan in old age","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1126\/science.1099480","article-title":"Overriding imatinib resistance with a novel ABL kinase inhibitor","volume":"305","author":"Shah","year":"2004","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/pca.70008","article-title":"A Comprehensive Overview of Quercetin: Chemistry, Analytical Approaches, Formulations, and Therapeutic Approaches","volume":"36","author":"Passi","year":"2025","journal-title":"Phytochem. Anal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41591-023-02543-w","article-title":"Senolytic therapy in mild Alzheimer\u2019s disease: A phase 1 feasibility trial","volume":"29","author":"Gonzales","year":"2023","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11738","DOI":"10.18632\/aging.202868","article-title":"Administration of quercetin improves mitochondria quality control and protects the neurons in 6-OHDA-lesioned Parkinson\u2019s disease models","volume":"13","author":"Wang","year":"2021","journal-title":"Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151554","DOI":"10.1016\/j.acthis.2020.151554","article-title":"Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition","volume":"122","author":"Firgany","year":"2020","journal-title":"Acta Histochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"572","DOI":"10.18632\/aging.203835","article-title":"Combination of dasatinib and quercetin improves cognitive abilities in aged male Wistar rats, alleviates inflammation and changes hippocampal synaptic plasticity and histone H3 methylation profile","volume":"14","author":"Krzystyniak","year":"2022","journal-title":"Aging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/s41593-024-01634-2","article-title":"Targeting pathological cells with senolytic drugs reduces seizures in neurodevelopmental mTOR-related epilepsy","volume":"27","author":"Ribierre","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114260","DOI":"10.1016\/j.bbr.2022.114260","article-title":"Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus","volume":"440","author":"Wang","year":"2023","journal-title":"Behav. Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, J., Lu, Y., Carr, C., Dhandapani, K.M., and Brann, D.W. (2023). Senolytic therapy is neuroprotective and improves functional outcome long-term after traumatic brain injury in mice. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1227705"},{"key":"ref_26","first-page":"667","article-title":"Quercetin promotes neurite growth through enhancing intracellular cAMP level and GAP-43 expression","volume":"13","author":"Chen","year":"2015","journal-title":"Chin. J. Nat. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.2147\/IJN.S191878","article-title":"Superparamagnetic iron oxide nanoparticles combined with NGF and quercetin promote neuronal branching morphogenesis of PC12 cells","volume":"14","author":"Katebi","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1111\/1440-1681.13573","article-title":"Quercetin promotes locomotor function recovery and axonal regeneration through induction of autophagy after spinal cord injury","volume":"48","author":"Wang","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s41232-022-00245-3","article-title":"Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: Experiments in a rat model of brachial plexus avulsion","volume":"42","author":"Huang","year":"2022","journal-title":"Inflamm. Regen."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/s10571-025-01580-y","article-title":"Senolytic Treatment Attenuates Global Ischemic Brain Injury and Enhances Cognitive Recovery by Targeting Mitochondria","volume":"45","author":"Gu","year":"2025","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"156772","DOI":"10.1016\/j.phymed.2025.156772","article-title":"Senolytic treatment alleviates cochlear senescence and delays age-related hearing loss in C57BL\/6J mice","volume":"142","author":"Chen","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2008.01.047","article-title":"Selective tonicity-induced expression of the neutral amino-acid transporter SNAT2 in oligodendrocytes in rat brain following systemic hypertonicity","volume":"153","author":"Maallem","year":"2008","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hellsten, S.V., Tripathi, R., Ceder, M.M., and Fredriksson, R. (2018). Nutritional Stress Induced by Amino Acid Starvation Results in Changes for Slc38 Transporters in Immortalized Hypothalamic Neuronal Cells and Primary Cortex Cells. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00045"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1567-133X(01)00018-7","article-title":"Microarray analysis of brain RNA in mice with methylenetetrahydrofolate reductase deficiency and hyperhomocysteinemia","volume":"1","author":"Chen","year":"2002","journal-title":"Brain Res. Gene Expr. Patterns"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.15252\/emmm.201707993","article-title":"A complex genomic locus drives mtDNA replicase POLG expression to its disease-related nervous system regions","volume":"10","author":"Nikkanen","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1038\/sj.emboj.7600202","article-title":"Meteorin: A secreted protein that regulates glial cell differentiation and promotes axonal extension","volume":"23","author":"Nishino","year":"2004","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.nbd.2010.09.003","article-title":"Lentiviral delivery of meteorin protects striatal neurons against excitotoxicity and reverses motor deficits in the quinolinic acid rat model","volume":"41","author":"Emerich","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/jcbfm.2011.156","article-title":"Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke-induced striatal neurogenesis","volume":"32","author":"Wang","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wright, J.L., Ermine, C.M., J\u00f8rgensen, J.R., Parish, C.L., and Thompson, L.H. (2016). Over-Expression of Meteorin Drives Gliogenesis Following Striatal Injury. Front. Cell. Neurosci., 10.","DOI":"10.3389\/fncel.2016.00177"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109708","DOI":"10.1016\/j.exer.2023.109708","article-title":"Longitudinal in vivo evaluation of retinal ganglion cell complex layer and dendrites in mice with experimental autoimmune encephalomyelitis","volume":"237","author":"Qian","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1093\/bioinformatics\/btr390","article-title":"Simple Neurite Tracer: Open source software for reconstruction, visualization and analysis of neuronal processes","volume":"27","author":"Longair","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nmeth.3125","article-title":"Neuronal morphometry directly from bitmap images","volume":"11","author":"Ferreira","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, W.Y., Bin, X., Xu, Y., Chen, S., Zhou, S., Chen, S., Cao, Y., Qiu, K., and Ng, T.K. (2025). The Profile of Retinal Ganglion Cell Death and Cellular Senescence in Mice with Aging. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125436"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:46:39Z","timestamp":1766065599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/12170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":44,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262412170"],"URL":"https:\/\/doi.org\/10.3390\/ijms262412170","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}