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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 on 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 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":"10.1101\/2023.02.21.529410","type":"posted-content","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T23:15:19Z","timestamp":1677021319000},"source":"Crossref","is-referenced-by-count":7,"title":["Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Experimental Glaucoma and Optic Nerve Crush"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9422-490X","authenticated-orcid":false,"given":"Casey J.","family":"Keuthan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Schaub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weixiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Quillen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Kimball","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas V.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongkai","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald J.","family":"Zack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry A.","family":"Quigley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023052920253785000_2023.02.21.529410v3.1","doi-asserted-by":"publisher","DOI":"10.1097\/IJG.0b013e31806540a1"},{"key":"2023052920253785000_2023.02.21.529410v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2004.08.003"},{"key":"2023052920253785000_2023.02.21.529410v3.3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200706181"},{"key":"2023052920253785000_2023.02.21.529410v3.4","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1981.03930010635009"},{"key":"2023052920253785000_2023.02.21.529410v3.5","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22058"},{"key":"2023052920253785000_2023.02.21.529410v3.6","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e31817841cb"},{"key":"2023052920253785000_2023.02.21.529410v3.7","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199707)20:3<262::AID-GLIA10>3.0.CO;2-S"},{"issue":"8","key":"2023052920253785000_2023.02.21.529410v3.8","doi-asserted-by":"crossref","first-page":"e0238104","DOI":"10.1371\/journal.pone.0238104","article-title":"Astrocyte responses to experimental glaucoma in mouse optic nerve head","volume":"15","year":"2020","journal-title":"PLoS One"},{"key":"2023052920253785000_2023.02.21.529410v3.9","first-page":"453","article-title":"Integrins in the optic nerve head: potential roles in glaucomatous optic neuropathy (an American Ophthalmological Society thesis)","volume":"104","year":"2006","journal-title":"Trans Am Ophthalmol Soc"},{"key":"2023052920253785000_2023.02.21.529410v3.10","doi-asserted-by":"crossref","unstructured":"Forrest, S.L. , et al., Distribution Patterns of Astrocyte Populations in the Human Cortex. 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