{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:54:43Z","timestamp":1760237683763,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","award":["30633"],"award-info":[{"award-number":["30633"]}],"id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2015-05084"],"award-info":[{"award-number":["RGPIN-2015-05084"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the present study, we hypothesized that the microtubule-associated protein Tau may influence retinal neuron survival and axonal regeneration after optic nerve injury. To test this hypothesis, the density of retinal ganglion cells was evaluated by immunostaining retinal flat-mounts for RNA-binding protein with multiple splicing (RBPMS) two weeks after optic nerve micro-crush lesion in Tau-deprived (Tau knock-out (KO)) and wild-type (WT) mice. Axon growth was determined on longitudinal sections of optic nerves after anterograde tracing. Our results showed that the number of surviving retinal ganglion cells and growing axons did not significantly vary between WT and Tau KO animals. Moreover, sustained activation of the neuronal growth program with ciliary neurotrophic factor (CNTF) resulted in a similar increase in surviving neurons and in growing axons in WT and Tau KO mice. Taken together, our data suggest that Tau does not influence axonal regeneration or neuronal survival.<\/jats:p>","DOI":"10.3390\/ijms21114100","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T05:16:14Z","timestamp":1591679774000},"page":"4100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tau Gene Deletion Does Not Influence Axonal Regeneration and Retinal Neuron Survival in the Injured Mouse Visual System"],"prefix":"10.3390","volume":"21","author":[{"given":"L\u00e9a","family":"Rodriguez","sequence":"first","affiliation":[{"name":"CUO-Recherche, D\u00e9partement d\u2019ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 Laval and Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Joly","sequence":"additional","affiliation":[{"name":"CUO-Recherche, D\u00e9partement d\u2019ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 Laval and Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius Baya","family":"Mdzomba","sequence":"additional","affiliation":[{"name":"CUO-Recherche, D\u00e9partement d\u2019ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 Laval and Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Pernet","sequence":"additional","affiliation":[{"name":"CUO-Recherche, D\u00e9partement d\u2019ophtalmologie, Facult\u00e9 de m\u00e9decine, Universit\u00e9 Laval and Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Quebec, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rodriguez, L., Mdzomba, J.B., Joly, S., Boudreau-Laprise, M., Planel, E., and Pernet, V. (2018). Human Tau Expression Does Not Induce Mouse Retina Neurodegeneration, Suggesting Differential Toxicity of Tau in Brain vs. Retinal Neurons. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00293"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1523\/JNEUROSCI.3986-15.2016","article-title":"Tau Accumulation, Altered Phosphorylation, and Missorting Promote Neurodegeneration in Glaucoma","volume":"36","author":"Chiasseu","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1523\/JNEUROSCI.22-10-03977.2002","article-title":"TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo","volume":"22","author":"Cheng","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0891-0618(01)00096-5","article-title":"Accumulation of C-terminally truncated tau protein associated with vulnerability of the perforant pathway in early stages of neurofibrillary pathology in Alzheimer\u2019s disease","volume":"22","author":"Wischik","year":"2001","journal-title":"J. Chem. Neuroanat."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chiasseu, M., Alarcon-Martinez, L., Belforte, N., Quintero, H., Dotigny, F., Destroismaisons, L., Vande Velde, C., Panayi, F., Louis, C., and Di Polo, A. (2017). Tau accumulation in the retina promotes early neuronal dysfunction and precedes brain pathology in a mouse model of Alzheimer\u2019s disease. Mol. Neurodegener., 12.","DOI":"10.1186\/s13024-017-0199-3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1091\/mbc.02-03-0046","article-title":"Protein kinase MARK\/PAR-1 is required for neurite outgrowth and establishment of neuronal polarity","volume":"13","author":"Biernat","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/cne.903580209","article-title":"Distribution of Big tau in the central nervous system of the adult and developing rat","volume":"358","author":"Boyne","year":"1995","journal-title":"J. Comp. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E5454","DOI":"10.1073\/pnas.1621225114","article-title":"Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity","volume":"114","author":"Leibinger","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1523\/JNEUROSCI.4885-10.2011","article-title":"Taxol facilitates axon regeneration in the mature CNS","volume":"31","author":"Sengottuvel","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1523\/JNEUROSCI.14-07-04368.1994","article-title":"Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats","volume":"14","author":"Berkelaar","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1126\/science.1161566","article-title":"Promoting axon regeneration in the adult CNS by modulation of the PTEN\/mTOR pathway","volume":"322","author":"Park","year":"2008","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.mcn.2004.10.011","article-title":"Receptor protein tyrosine phosphatase sigma inhibits axon regrowth in the adult injured CNS","volume":"28","author":"Sapieha","year":"2005","journal-title":"Mol. Cell Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1167\/iovs.09-4098","article-title":"RNA binding protein with multiple splicing: A new marker for retinal ganglion cells","volume":"51","author":"Kwong","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1111\/j.1460-9568.2006.05230.x","article-title":"Cooperative effects of bcl-2 and AAV-mediated expression of CNTF on retinal ganglion cell survival and axonal regeneration in adult transgenic mice","volume":"24","author":"Leaver","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_18","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":"Muller","year":"2009","journal-title":"Mol. Cell Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14334","DOI":"10.1523\/JNEUROSCI.2770-09.2009","article-title":"Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor","volume":"29","author":"Leibinger","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1167\/iovs.09-4203","article-title":"Stimulation of axon regeneration in the mature optic nerve by intravitreal application of the toll-like receptor 2 agonist Pam3Cys","volume":"51","author":"Hauk","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Leibinger, M., Andreadaki, A., Diekmann, H., and Fischer, D. (2013). Neuronal STAT3 activation is essential for CNTF- and inflammatory stimulation-induced CNS axon regeneration. Cell Death Dis., 4.","DOI":"10.1038\/cddis.2013.310"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Joly, S., Dalkara, D., and Pernet, V. (2017). Sphingosine 1-Phosphate Receptor 1 Modulates CNTF-Induced Axonal Growth and Neuroprotection in the Mouse Visual System. Neural. Plast, 2017.","DOI":"10.1155\/2017\/6818970"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Klimczak, R.R., Koerber, J.T., Dalkara, D., Flannery, J.G., and Schaffer, D.V. (2009). A novel adeno-associated viral variant for efficient and selective intravitreal transduction of rat Muller cells. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007467"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1091\/mbc.12.1.171","article-title":"Competition for microtubule-binding with dual expression of tau missense and splice isoforms","volume":"12","author":"Lu","year":"2001","journal-title":"Mol. Biol Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1083\/jcb.124.5.769","article-title":"Identification of a novel microtubule binding and assembly domain in the developmentally regulated inter-repeat region of tau","volume":"124","author":"Goode","year":"1994","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1083\/jcb.115.3.717","article-title":"Tau protein binds to microtubules through a flexible array of distributed weak sites","volume":"115","author":"Butner","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pernet, V., Joly, S., Jordi, N., Dalkara, D., Guzik-Kornacka, A., Flannery, J.G., and Schwab, M.E. (2013). Misguidance and modulation of axonal regeneration by Stat3 and Rho\/ROCK signaling in the transparent optic nerve. Cell Death Dis., 4.","DOI":"10.1038\/cddis.2013.266"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1523\/JNEUROSCI.2281-17.2017","article-title":"The Microtubule-Associated Protein Tau Mediates the Organization of Microtubules and Their Dynamic Exploration of Actin-Rich Lamellipodia and Filopodia of Cortical Growth Cones","volume":"38","author":"Biswas","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.neuron.2011.04.009","article-title":"The many faces of tau","volume":"70","author":"Morris","year":"2011","journal-title":"Neuron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1167\/iovs.19-26683","article-title":"Tau Is Involved in Death of Retinal Ganglion Cells of Rats From Optic Nerve Crush","volume":"60","author":"Oku","year":"2019","journal-title":"Invest. Ophthalmol Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1006\/exnr.2000.7573","article-title":"Retinal ganglion cell and nonneuronal cell responses to a microcrush lesion of adult rat optic nerve","volume":"167","author":"Ellezam","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1523\/JNEUROSCI.23-06-02284.2003","article-title":"Macrophage-derived factors stimulate optic nerve regeneration","volume":"23","author":"Yin","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_33","first-page":"764","article-title":"Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma","volume":"41","author":"Pease","year":"2000","journal-title":"Invest. Ophthalmol Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1523\/JNEUROSCI.10-08-02834.1990","article-title":"Selective impairment of slow axonal transport after optic nerve injury in adult rats","volume":"10","author":"McKerracher","year":"1990","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1523\/JNEUROSCI.20-12-04615.2000","article-title":"Lens injury stimulates axon regeneration in the mature rat optic nerve","volume":"20","author":"Leon","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"9169","DOI":"10.1523\/JNEUROSCI.0612-07.2007","article-title":"Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration","volume":"27","author":"Erturk","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"391","DOI":"10.4161\/cib.15552","article-title":"Facilitating axon regeneration in the injured CNS by microtubules stabilization","volume":"4","author":"Sengottuvel","year":"2011","journal-title":"Commun. Integr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nm.2600","article-title":"Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury","volume":"18","author":"Erturk","year":"2011","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/369488a0","article-title":"Altered microtubule organization in small-calibre axons of mice lacking tau protein","volume":"369","author":"Harada","year":"1994","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1083\/jcb.150.5.989","article-title":"Defects in axonal elongation and neuronal migration in mice with disrupted tau and map1b genes","volume":"150","author":"Takei","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1083\/jcb.137.7.1615","article-title":"Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B (MAP1B) gene","volume":"137","author":"Takei","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1083\/jcb.151.6.1169","article-title":"MAP1B is required for axon guidance and Is involved in the development of the central and peripheral nervous system","volume":"151","author":"Meixner","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1073\/pnas.93.3.1270","article-title":"Neuronal abnormalities in microtubule-associated protein 1B mutant mice","volume":"93","author":"Edelmann","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rodriguez, L., Joly, S., Zine-Eddine, F., Mdzomba, J.B., and Pernet, V. (2020). Tau modulates visual plasticity in adult and aging mice. Neurobiol. Aging, under review.","DOI":"10.1016\/j.neurobiolaging.2020.07.024"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1523\/JNEUROSCI.5242-07.2008","article-title":"Axonal transport rates in vivo are unaffected by tau deletion or overexpression in mice","volume":"28","author":"Yuan","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1046\/j.1460-9568.2002.01977.x","article-title":"Partial regeneration and long-term survival of rat retinal ganglion cells after optic nerve crush is accompanied by altered expression, phosphorylation and distribution of cytoskeletal proteins","volume":"15","author":"Dieterich","year":"2002","journal-title":"Eur J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/cne.20304","article-title":"Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter","volume":"480","author":"Badea","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1167\/iovs.05-1295","article-title":"Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model","volume":"47","author":"Li","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_50","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_51","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_52","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.1069609","article-title":"Melanopsin-containing retinal ganglion cells: Architecture, projections, and intrinsic photosensitivity","volume":"295","author":"Hattar","year":"2002","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/82868","article-title":"Neurotrophins are required for nerve growth during development","volume":"4","author":"Tucker","year":"2001","journal-title":"Nat. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:36:53Z","timestamp":1760175413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/11\/4100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,8]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijms21114100"],"URL":"https:\/\/doi.org\/10.3390\/ijms21114100","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,6,8]]}}}