{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T23:42:29Z","timestamp":1777851749969,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Oxstem Ltd"},{"name":"Oxstem Ltd"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>\n                    Retinal astrocytes are vital for neuronal homeostasis in the retina. Together with M\u00fcller glia, they provide retinal cells with neurotrophic factors, antioxidative support, and defense mechanisms such as the formation of the blood-retinal barrier. Substantial heterogeneity of astrocyte morphology and function represents a challenge for identification of distinct subtypes which may be potential targets for therapeutic purposes. Hence, identification of novel markers of astrocyte subpopulations is highly relevant to better understand the molecular mechanisms involved in retinal development, homeostasis, and pathology. In this study, we observed that the cell cycle regulator, p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    , is expressed in immature astrocytes in the mouse retina. Immunohistochemical analysis showed p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression in the optic nerve of wild-type mice from 3 days to 3 months of age and in the nerve fiber layer of the adult mouse retina. Colocalization of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression and glial fibrillary acidic protein (immature\/mature astrocyte marker) tends to decrease with age. However, colocalization of p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    expression and vimentin (immature astrocyte marker) remains high in the optic nerve from the early postnatal period to adulthood. The observations from this study provide a valuable tool for further investigations of ocular astrocytes in the developing retina as well as in degenerative retinopathies.\n                  <\/jats:p>","DOI":"10.1369\/00221554231184286","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T15:02:19Z","timestamp":1687618939000},"page":"301-320","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Developmental Expression of the Cell Cycle Regulator p16\n                    <sup>INK4a<\/sup>\n                    in Retinal Glial Cells: A Novel Marker for Immature Ocular Astrocytes?"],"prefix":"10.1369","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-6162","authenticated-orcid":false,"given":"Cristina","family":"Martinez-Fernandez de la Camara","sequence":"first","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-4072","authenticated-orcid":false,"given":"Tina","family":"Storm","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4300-2033","authenticated-orcid":false,"given":"Ahmed","family":"Salman","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8428-720X","authenticated-orcid":false,"given":"Thomas","family":"Burgoyne","sequence":"additional","affiliation":[{"name":"Institute of Ophthalmology, University College London, London, United Kingdom"},{"name":"Paediatric Respiratory Medicine, Primary Ciliary Dyskinesia Centre, Royal Brompton & Harefield NHS Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Qvist","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry O.","family":"Orlans","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela J.","family":"Russell","sequence":"additional","affiliation":[{"name":"Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Pharmacology, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G.","family":"Davies","sequence":"additional","affiliation":[{"name":"Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alun R.","family":"Barnard","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"MacLaren","sequence":"additional","affiliation":[{"name":"Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom"},{"name":"Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"bibr1-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1038\/332834a0","volume":"332","author":"Watanabe T","year":"1988","journal-title":"Nature"},{"key":"bibr2-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0619-8"},{"key":"bibr3-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.06.003"},{"key":"bibr4-00221554231184286","volume":"117","author":"Su J","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"bibr5-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1136\/bjo.80.5.458","volume":"80","author":"MacLaren RE","year":"1996","journal-title":"Br J Ophthalmol"},{"key":"bibr6-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2954721"},{"key":"bibr7-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1134\/S000629791809002X"},{"issue":"12","key":"bibr8-00221554231184286","volume":"243","author":"Tao C","year":"2014","journal-title":"Dev Dyn"},{"key":"bibr9-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.027"},{"key":"bibr10-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902550104"},{"key":"bibr11-00221554231184286","volume":"286","author":"Ling TL","year":"1989","journal-title":"J Comp Neurol"},{"issue":"11","key":"bibr12-00221554231184286","volume":"15","author":"Chu Y","year":"2001","journal-title":"FASEB J"},{"key":"bibr13-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2018-205216"},{"key":"bibr14-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1997.3824"},{"key":"bibr15-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.614"},{"key":"bibr16-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.93.24.13742","volume":"93","author":"Alcorta DA","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"bibr17-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183653"},{"key":"bibr18-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3960"},{"key":"bibr19-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.10.005","volume":"179","author":"Gorgoulis V","year":"2019","journal-title":"Cell"},{"key":"bibr20-00221554231184286","first-page":"1332","volume":"12","author":"Safwan-Zaiter H","year":"2022","journal-title":"Life (Basel)"},{"key":"bibr21-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.11.012"},{"key":"bibr22-00221554231184286","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.3390\/ijms18071591","volume":"18","author":"D\u2019Arcangelo D","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"3","key":"bibr23-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1016\/S1535-6108(02)00046-6","volume":"1","author":"Bachoo RM","year":"2002","journal-title":"Cancer Cell"},{"key":"bibr24-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2020.05.002","volume":"32","author":"Grosse L","year":"2020","journal-title":"Cell Metab"},{"issue":"7","key":"bibr25-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1038\/s41551-018-0219-9","volume":"2","author":"Tekin H","year":"2018","journal-title":"Nat Biomed Eng"},{"key":"bibr26-00221554231184286","volume":"32","author":"Gu Z","year":"2016","journal-title":"Bioinformatics"},{"key":"bibr27-00221554231184286","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2019"},{"key":"bibr28-00221554231184286","unstructured":"Abcam. Anti\u2014CDKN2A\/p16INK4a antibody\u2014N-terminal(ab189034). 1998\u20132023. https:\/\/www.abcam.com\/products\/primary-antibodies\/cdkn2ap16ink4a-antibody-n-terminal-ab189034.html"},{"key":"bibr29-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1016\/j.conb.2017.08.005","volume":"47","author":"MacDonald RB","year":"2017","journal-title":"Curr Opin Neurobiol"},{"key":"bibr30-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2015.05.002","volume":"161","author":"Macosko EZ","year":"2015","journal-title":"Cell"},{"issue":"9","key":"bibr31-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0075067","volume":"8","author":"Chidlow G","year":"2013","journal-title":"Plos One"},{"key":"bibr32-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070918-050443"},{"issue":"6","key":"bibr33-00221554231184286","volume":"18","author":"Sun D","year":"2012","journal-title":"Neuroscientist"},{"key":"bibr34-00221554231184286","volume":"65","author":"Li Z","year":"2020","journal-title":"Curr Opin Genet Dev"},{"issue":"7","key":"bibr35-00221554231184286","volume":"27","author":"Kivel\u00e4 T","year":"1986","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bibr36-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1002\/cne.22335","volume":"518","author":"Stanke J","year":"2010","journal-title":"J Comp Neurol"},{"key":"bibr37-00221554231184286","volume":"118","author":"Nilsson K","year":"2006","journal-title":"Int J Cancer"},{"key":"bibr38-00221554231184286","doi-asserted-by":"publisher","DOI":"10.1080\/10520290310001659466"},{"issue":"22","key":"bibr39-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1002\/pmic.200700133","volume":"7","author":"Souza-Rodr\u00edgues E","year":"2007","journal-title":"Proteomics"},{"issue":"1","key":"bibr40-00221554231184286","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/(SICI)1098-1136(199601)16:1<27::AID-GLIA4>3.0.CO;2-8","volume":"16","author":"Orentas DM","year":"1996","journal-title":"Glia"},{"issue":"10","key":"bibr41-00221554231184286","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0139664","volume":"10","author":"Lamoke F","year":"2015","journal-title":"Plos One"}],"container-title":["Journal of Histochemistry &amp; Cytochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/00221554231184286","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1369\/00221554231184286","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/00221554231184286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:25:50Z","timestamp":1777501550000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1369\/00221554231184286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1369\/00221554231184286"],"URL":"https:\/\/doi.org\/10.1369\/00221554231184286","relation":{},"ISSN":["0022-1554","1551-5044"],"issn-type":[{"value":"0022-1554","type":"print"},{"value":"1551-5044","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6]]}}}