{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:57:25Z","timestamp":1773277045091,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:00:00Z","timestamp":1693958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PHS research","award":["EY 02120"],"award-info":[{"award-number":["EY 02120"]}]},{"name":"PHS research","award":["5P30EY001765"],"award-info":[{"award-number":["5P30EY001765"]}]},{"name":"PHS research","award":["R01HG009518"],"award-info":[{"award-number":["R01HG009518"]}]},{"name":"Wilmer Eye Institute Core","award":["EY 02120"],"award-info":[{"award-number":["EY 02120"]}]},{"name":"Wilmer Eye Institute Core","award":["5P30EY001765"],"award-info":[{"award-number":["5P30EY001765"]}]},{"name":"Wilmer Eye Institute Core","award":["R01HG009518"],"award-info":[{"award-number":["R01HG009518"]}]},{"name":"NIH","award":["EY 02120"],"award-info":[{"award-number":["EY 02120"]}]},{"name":"NIH","award":["5P30EY001765"],"award-info":[{"award-number":["5P30EY001765"]}]},{"name":"NIH","award":["R01HG009518"],"award-info":[{"award-number":["R01HG009518"]}]},{"name":"Guerrieri Family Foundation","award":["EY 02120"],"award-info":[{"award-number":["EY 02120"]}]},{"name":"Guerrieri Family Foundation","award":["5P30EY001765"],"award-info":[{"award-number":["5P30EY001765"]}]},{"name":"Guerrieri Family Foundation","award":["R01HG009518"],"award-info":[{"award-number":["R01HG009518"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and separately micro-dissected unmyelinated and myelinated optic nerve regions from na\u00efve C57BL\/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the na\u00efve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor \u03b2 pathways, as well as extracellular matrix\u2013receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.<\/jats:p>","DOI":"10.3390\/ijms241813719","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T10:07:37Z","timestamp":1693994857000},"page":"13719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-490X","authenticated-orcid":false,"given":"Casey J.","family":"Keuthan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Schaub","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-5302","authenticated-orcid":false,"given":"Sarah","family":"Quillen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9125-3444","authenticated-orcid":false,"given":"Elizabeth","family":"Kimball","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5372-5457","authenticated-orcid":false,"given":"Thomas V.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongkai","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald J.","family":"Zack","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"},{"name":"Departments of Neuroscience, Molecular Biology and Genetics, and Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry A.","family":"Quigley","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/IJG.0b013e31806540a1","article-title":"Risk factors and open-angle glaucoma: Classification and application","volume":"16","author":"Boland","year":"2007","journal-title":"J. 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