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Currently, there is no effective treatment that can protect vision for those with RP. In recent decades, the rd1 mouse has been used to study the pathological mechanisms of RP. Molecular biological studies using rd1 mice have clarified the mechanism of the apoptosis of photoreceptor cells in the early stage of RP. However, the pathological changes in RP over time remain unclear. The unknown pathology mechanism of RP over time and the difficulty of clinical treatment make it urgent to perform more refined and spatially informed molecular biology studies of RP. In this study, spatial transcriptomic analysis is used to study the changes in different retinal layers of rd1 mice at different ages. The results demonstrate the pattern of photoreceptor apoptosis between rd1 mice and the control group. Not only was oxidative stress enhanced in the late stage of RP, but it was accompanied by an up-regulation of the VEGF pathway. Analysis of temporal kinetic trends has further identified patterns of changes in the key pathways of the early and late stages, to help understand the important pathogenesis of RP. Overall, the application of spatial transcriptomics to rd1 mice can help to elucidate the important pathogenesis of RP involving photoreceptor apoptosis and retinal remodeling.<\/jats:p>","DOI":"10.3390\/ijms241914869","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T09:43:01Z","timestamp":1696326181000},"page":"14869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatial Transcriptomic Analysis Reveals Regional Transcript Changes in Early and Late Stages of rd1 Model Mice with Retinitis Pigmentosa"],"prefix":"10.3390","volume":"24","author":[{"given":"Ying","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Sheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Medicine, Southeast University, Nanjing 210097, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-5915","authenticated-orcid":false,"given":"Jing","family":"Tu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0678-5219","authenticated-orcid":false,"given":"Xiangwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-1949","authenticated-orcid":false,"given":"Qinyu","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhong","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, Nanjing 210096, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s12035-008-8045-9","article-title":"Photoreceptor Cell Death Mechanisms in Inherited Retinal Degeneration","volume":"38","author":"Kustermann","year":"2008","journal-title":"Mol. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"18","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1186\/s13287-020-01925-y","article-title":"Peripheral blood-derived monocytes show neuronal properties and integration in immune-deficient rd1 mouse model upon phenotypic differentiation and induction with retinal growth factors","volume":"11","author":"Mishra","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/347677a0","article-title":"Retinal degeneration in the rd mouse is caused by a defect in the \u03b2 subunit of rod cGMP-phosphodiesterase","volume":"347","author":"Bowes","year":"1990","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.visres.2006.11.020","article-title":"Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene","volume":"47","author":"Chang","year":"2007","journal-title":"Vision Res."},{"key":"ref_6","first-page":"100772","article-title":"Cellular mechanisms of hereditary photoreceptor degeneration\u2014Focus on cGMP","volume":"74","author":"Sparrow","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100771","DOI":"10.1016\/j.preteyeres.2019.07.004","article-title":"Persistent remodeling and neurodegeneration in late-stage retinal degeneration","volume":"74","author":"Pfeiffer","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.4103\/1673-5374.361537","article-title":"Stem cell therapy in retinal diseases","volume":"18","author":"Voisin","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100975","DOI":"10.1016\/j.preteyeres.2021.100975","article-title":"Early and late-stage gene therapy interventions for inherited retinal degenerations","volume":"86","author":"Botto","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1042\/BST20180138","article-title":"Photoreceptor actin dysregulation in syndromic and non-syndromic retinitis pigmentosa","volume":"46","author":"Megaw","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, M., So, K.F., Lam, W.C., and Lo, A. (2021). Cell Ferroptosis: New Mechanism and New Hope for Retinitis Pigmentosa. Cells, 10.","DOI":"10.3390\/cells10082153"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1093\/hmg\/ddac013","article-title":"Multiomics analyses reveal early metabolic imbalance and mitochondrial stress in neonatal photoreceptors leading to cell death in Pde6brd1\/rd1 mouse model of retinal degeneration","volume":"31","author":"Jiang","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1074\/mcp.M300029-MCP200","article-title":"Differential proteomic analysis of the mouse retina: The induction of crystallin proteins by retinal degeneration in the rd1 mouse","volume":"2","author":"Cavusoglu","year":"2003","journal-title":"Mol. Cell Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"590572","DOI":"10.3389\/fphar.2020.590572","article-title":"Thioredoxin Delays Photoreceptor Degeneration, Oxidative and Inflammation Alterations in Retinitis Pigmentosa","volume":"11","author":"Olivar","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1167\/iovs.03-1184","article-title":"Identification of gene expression changes associated with the progression of retinal degeneration in the rd1 mouse","volume":"45","author":"Hackam","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3109\/02713683.2012.688163","article-title":"Optic Nerve Head, Retinal Nerve Fiber Layer, and Macular Thickness Measurements in Young Patients with Retinitis Pigmentosa","volume":"37","author":"Hwang","year":"2012","journal-title":"Curr. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1007\/s10792-021-01964-1","article-title":"Optical coherence tomography biomarkers of photoreceptor degeneration in retinitis pigmentosa","volume":"41","author":"Gong","year":"2021","journal-title":"Int. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1001\/archopht.1997.01100150513011","article-title":"Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis","volume":"115","author":"Santos","year":"1997","journal-title":"Arch. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s41587-022-01648-w","article-title":"Spatial transcriptomics for profiling the tropism of viral vectors in tissues","volume":"41","author":"Jang","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12139","DOI":"10.1038\/ncomms12139","article-title":"Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling","volume":"7","author":"Nichterwitz","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25A-1","DOI":"10.1002\/0471142727.mb25a01s112","article-title":"Laser Microdissection","volume":"112","author":"Frost","year":"2015","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e10518","DOI":"10.7554\/eLife.10518","article-title":"Temporal transcriptomics suggest that twin-peaking genes reset the clock","volume":"4","author":"Pembroke","year":"2015","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zechel, S., Zajac, P., Lonnerberg, P., Ibanez, C.F., and Linnarsson, S. (2014). Topographical transcriptome mapping of the mouse medial ganglionic eminence by spatially resolved RNA-seq. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0486-z"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vingolo, E.M., Casillo, L., Contento, L., Toja, F., and Florido, A. (2022). Retinitis Pigmentosa (RP): The Role of Oxidative Stress in the Degenerative Process Progression. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030582"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s10792-009-9337-4","article-title":"Successful treatment of choroidal neovascular membrane in retinitis pigmentosa with intravitreal bevacizumab","volume":"30","author":"Malik","year":"2010","journal-title":"Int. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Miyata, M., Oishi, A., Oishi, M., Hasegawa, T., Ikeda, H.O., and Tsujikawa, A. (2018). Long-term efficacy and safety of anti-VEGF therapy in retinitis pigmentosa: A case report. BMC Ophthalmol., 18.","DOI":"10.1186\/s12886-018-0914-z"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5575851","DOI":"10.1155\/2021\/5575851","article-title":"Outer Macular Microvascular Supply in Retinitis Pigmentosa Examined using Optical Coherence Tomography Angiography","volume":"2021","author":"Hong","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10368","DOI":"10.1073\/pnas.181329198","article-title":"An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration","volume":"98","author":"Lahdenranta","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Broggini, T., Stange, L., Lucia, K.E., Vajkoczy, P., and Czabanka, M. (2022). Endothelial EphrinB2 Regulates Sunitinib Therapy Response in Murine Glioma. Life, 12.","DOI":"10.3390\/life12050691"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4084","DOI":"10.1167\/iovs.19-26767","article-title":"Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy","volume":"60","author":"Li","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1084\/jem.20132330","article-title":"Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells","volume":"211","author":"Raimondi","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/dneu.20821","article-title":"Ephrin-B2 elicits differential growth cone collapse and axon retraction in retinal ganglion cells from distinct retinal regions","volume":"70","author":"Petros","year":"2010","journal-title":"Dev. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nature08995","article-title":"Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis","volume":"465","author":"Sawamiphak","year":"2010","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09002","article-title":"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis","volume":"465","author":"Wang","year":"2010","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/S0898-6568(03)00072-X","article-title":"Role of ephrin B2 in human retinal endothelial cell proliferation and migration","volume":"15","author":"Steinle","year":"2003","journal-title":"Cell. Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1097-2765(02)00488-4","article-title":"EphrinB phosphorylation and reverse signaling: Regulation by Src kinases and PTP-BL phosphatase","volume":"9","author":"Palmer","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1182\/blood-2011-09-380006","article-title":"Blocking ephrinB2 with highly specific antibodies inhibits angiogenesis, lymphangiogenesis, and tumor growth","volume":"119","author":"Abengozar","year":"2012","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103327","DOI":"10.1016\/j.isci.2021.103327","article-title":"Identification of early-onset photoreceptor degeneration in transgenic mouse models of Alzheimer\u2019s disease","volume":"24","author":"Zhang","year":"2021","journal-title":"Iscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.semcdb.2022.09.011","article-title":"Retinal organoids from human-induced pluripotent stem cells: From studying retinal dystrophies to early diagnosis of Alzheimer\u2019s and Parkinson\u2019s disease","volume":"144","author":"Echeverry","year":"2023","journal-title":"Semin. Cell Dev. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:04:44Z","timestamp":1760130284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,3]]},"references-count":41,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914869"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914869","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,3]]}}}