{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T20:49:50Z","timestamp":1777927790308,"version":"3.51.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Animal models of disease are paramount to understand retinal development, the pathophysiology of eye diseases, and to study neurodegeneration using optical coherence tomography (OCT) data. In this study, we present a comprehensive normative database of retinal thickness in C57BL6\/129S mice using spectral-domain OCT data. The database covers a longitudinal period of 16 months, from 1 to 16 months of age, and provides valuable insights into retinal development and changes over time. Our findings reveal that total retinal thickness decreases with age, while the thickness of individual retinal layers and layer aggregates changes in different ways. For example, the outer plexiform layer (OPL), photoreceptor inner segments (ILS), and retinal pigment epithelium (RPE) thickened over time, whereas other retinal layers and layer aggregates became thinner. Additionally, we compare the retinal thickness of wild-type (WT) mice with an animal model of Alzheimer's disease (3 \u00d7 Tg-AD) and show that the transgenic mice exhibit a decrease in total retinal thickness compared to age-matched WT mice, with statistically significant differences observed at all evaluated ages. This normative database of retinal thickness in mice will serve as a reference for future studies on retinal changes in neurodegenerative and eye diseases and will further our understanding of the pathophysiology of these conditions.<\/jats:p>","DOI":"10.3389\/fnagi.2023.1161847","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T05:04:29Z","timestamp":1680757469000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Ana","family":"Batista","sequence":"first","affiliation":[]},{"given":"Pedro","family":"Guimar\u00e3es","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Paula I.","family":"Moreira","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio Francisco","family":"Ambr\u00f3sio","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Castelo-Branco","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Serranho","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Bernardes","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e96494","DOI":"10.1371\/journal.pone.0096494","article-title":"Spectral-domain optical coherence tomography of the rodent eye: highlighting layers of the outer retina using signal averaging and comparison with histology","volume":"9","author":"Berger","year":"2014","journal-title":"PLoS ONE"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.5220\/0011125600003209","article-title":"\u201cShedding light on early central nervous system changes for alzheimer's disease through the retina: an animal study,\u201d","volume-title":"Proceedings of the 2nd International Conference on Image Processing and Vision Engineering (SCITEPRESS - Science and Technology Publications)","author":"Bernardes","year":"2022"},{"key":"B3","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.neuron.2005.01.040","article-title":"Intraneuronal A\u03b2 causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice","volume":"45","author":"Billings","year":"2005","journal-title":"Neuron"},{"key":"B4","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nature08983","article-title":"Neural mechanisms of ageing and cognitive decline","volume":"464","author":"Bishop","year":"2010","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"655","DOI":"10.3233\/JAD-160823","article-title":"Investigations into retinal pathology in the early stages of a mouse model of Alzheimer's disease","volume":"56","author":"Chidlow","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13195-019-0542-8","article-title":"Retinal thinning of inner sub-layers is associated with cortical atrophy in a mouse model of Alzheimer's disease: a longitudinal multimodal in vivo study","volume":"11","author":"Chiquita","year":"","journal-title":"Alzheimers. Res. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1093\/hmg\/ddz045","article-title":"A longitudinal multimodal in vivo molecular imaging study of the 3xTg-AD mouse model shows progressive early hippocampal and taurine loss","volume":"28","author":"Chiquita","year":"","journal-title":"Hum. Mol. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s40942-016-0049-4","article-title":"The role of optical coherence tomography in Alzheimer's disease","volume":"2","author":"Cunha","year":"2016","journal-title":"Int. J. Retin Vitreous."},{"key":"B9","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1037\/0033-2909.96.3.518","article-title":"Protein synthesis and memory: a review","volume":"96","author":"Davis","year":"1984","journal-title":"Psychol. Bull."},{"key":"B10","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3389\/fneur.2017.00701","article-title":"Optical coherence tomography in Alzheimer's disease and other neurodegenerative diseases","volume":"8","author":"Doustar","year":"2017","journal-title":"Front. Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1167\/iovs.62.7.9","article-title":"Age-related retinal changes in wild-type C57BL\/6J mice between 2 and 32 months","volume":"62","author":"Ferdous","year":"2021","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e67265","DOI":"10.1371\/journal.pone.0067265","article-title":"Retinal thickness normative data in wild-type mice using customized miniature SD-OCT","volume":"8","author":"Ferguson","year":"2013","journal-title":"PLoS ONE"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e111203","DOI":"10.1371\/journal.pone.0111203","article-title":"Retinal thickness measurement obtained with spectral domain optical coherence tomography assisted optical biopsy accurately correlates with ex vivo histology","volume":"9","author":"Ferguson","year":"2014","journal-title":"PLoS ONE"},{"key":"B15","doi-asserted-by":"publisher","first-page":"9433","DOI":"10.18632\/aging.202916","article-title":"Longitudinal normative OCT retinal thickness data for wild-type mice, and characterization of changes in the 3 \u00d7 Tg-AD mice model of Alzheimer's disease","volume":"13","author":"Ferreira","year":"2021","journal-title":"Aging"},{"key":"B16","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s12553-020-00413-w","article-title":"Characterization of the retinal changes of the 3 \u00d7 Tg-AD mouse model of Alzheimer's disease","volume":"10","author":"Ferreira","year":"2020","journal-title":"Health Technol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-18113-y","article-title":"Stage-independent biomarkers for Alzheimer's disease from the living retina: an animal study","volume":"12","author":"Ferreira","year":"2022","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"577","DOI":"10.3389\/fnagi.2022.832195","article-title":"Retinal aging in 3 \u00d7 Tg-AD mice model of Alzheimer's disease","volume":"14","author":"Guimar\u00e3es","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1117\/1.NPh.7.1.015006","article-title":"Retinal analysis of a mouse model of Alzheimer's disease with multicontrast optical coherence tomography","volume":"7","author":"Harper","year":"2020","journal-title":"Neurophotonics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnins.2021.785276","article-title":"Systematic phenotyping and characterization of the 3xTg-AD mouse model of Alzheimer's disease","volume":"15","author":"Javonillo","year":"2022","journal-title":"Front. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/j.clineuro.2011.02.014","article-title":"Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease","volume":"113","author":"Kesler","year":"2011","journal-title":"Clin. Neurol. Neurosurg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"16685","DOI":"10.1038\/s41598-019-53082-9","article-title":"Longitudinal OCT and OCTA monitoring reveals accelerated regression of hyaloid vessels in retinal degeneration 10 (rd10) mice","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.3390\/app12041860","article-title":"Quantitative optical coherence tomography for longitudinal monitoring of postnatal retinal development in developing mouse eyes","volume":"12","author":"Ma","year":"2022","journal-title":"Appl. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"5953","DOI":"10.1167\/iovs.13-12046","article-title":"Evaluation of retinal nerve fiber layer and ganglion cell layer thickness in Alzheimer's disease using spectral-domain optical coherence tomography","volume":"54","author":"Marziani","year":"2013","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1146\/annurev-animal-022114-110829","article-title":"Animal models of aging research: implications for human aging and age-related diseases","volume":"3","author":"Mitchell","year":"2015","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e0218826","DOI":"10.1371\/journal.pone.0218826","article-title":"Retinal texture biomarkers may help to discriminate between Alzheimer's, Parkinson's, and healthy controls","volume":"14","author":"Nunes","year":"2019","journal-title":"PLoS ONE"},{"key":"B27","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer's disease with plaques and tangles","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"B28","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1007\/978-3-319-24574-4_28","article-title":"\u201cU-Net: convolutional networks for biomedical image segmentation,\u201d","author":"Ronneberger","year":"2015","journal-title":"Lecture Notes in Computer Science"},{"key":"B29","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0301-0082(02)00126-0","article-title":"Impact of aging on hippocampal function: plasticity, network dynamics, and cognition","volume":"69","author":"Rosenzweig","year":"2003","journal-title":"Prog. Neurobiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnagi.2020.625642","article-title":"Retinal thickness changes over time in a murine AD model APPNL-F\/NL-F","volume":"12","author":"Salobrar-Garc\u00eda","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"16345","DOI":"10.1038\/s41598-018-34577-3","article-title":"Usefulness of peripapillary nerve fiber layer thickness assessed by optical coherence tomography as a biomarker for Alzheimer's disease","volume":"8","author":"S\u00e1nchez","year":"2018","journal-title":"Sci. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"7912","DOI":"10.1038\/s41598-020-64827-2","article-title":"Multimodal coherent imaging of retinal biomarkers of Alzheimer's disease in a mouse model","volume":"10","author":"Song","year":"2020","journal-title":"Sci. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.brainres.2010.06.011","article-title":"Characterization of the 3xTg-AD mouse model of Alzheimer's disease: part 2. Behavioral and cognitive changes","volume":"1348","author":"Sterniczuk","year":"2010","journal-title":"Brain Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.bbr.2015.04.012","article-title":"Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer's disease","volume":"289","author":"Stover","year":"2015","journal-title":"Behav. Brain Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1364\/OL.18.001864","article-title":"In vivo retinal imaging by optical coherence tomography","volume":"18","author":"Swanson","year":"1993","journal-title":"Opt. Lett."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.pmbts.2020.07.007","article-title":"Relevance of transgenic mouse models for Alzheimer's disease","volume":"177","author":"Tai","year":"2021","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41433-022-02056-9","article-title":"Optical coherence tomography as retinal imaging biomarker of neuroinflammation\/neurodegeneration in systemic disorders in adults and children","volume":"37","author":"Vujosevic","year":"2023","journal-title":"Eye"},{"key":"B38","doi-asserted-by":"publisher","first-page":"697621","DOI":"10.3389\/fnagi.2021.697621","article-title":"Functional aging in male C57BL\/6J mice across the life-span: a systematic behavioral analysis of motor, emotional, and memory function to define an aging phenotype","volume":"13","author":"Yanai","year":"2021","journal-title":"Front. Aging Neurosci."}],"updated-by":[{"DOI":"10.3389\/fnagi.2024.1423913","type":"corrigendum","label":"Corrigendum","source":"publisher","updated":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000}}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1161847\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T11:16:00Z","timestamp":1715339760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1161847\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,6]]},"references-count":38,"alternative-id":["10.3389\/fnagi.2023.1161847"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2023.1161847","relation":{"corrigendum":[{"id-type":"doi","id":"10.3389\/fnagi.2024.1423913","asserted-by":"object"}]},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,6]]},"article-number":"1161847"}}