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In the initial segment of the optic nerve directly behind the globe, the ganglion cell axons are unmyelinated and come into direct contact to astrocytes, suggesting that astrocytes may play a role in the pathology of glaucoma. As in other parts of the CNS, optic nerve head astrocytes respond to injury by characteristic changes in cell morphology and gene expression profile. Using RNA-sequencing of glaucomatous optic nerve heads, single-cell PCR, and an in-vivo assay, we demonstrate that an up-regulation of astrocytic phagocytosis is an early event after the onset of increased intraocular pressure. We also show that astrocytes in the glial lamina of the optic nerve are apparently functionally heterogeneous. At any time, even in na\u00efve nerves, some of the cells show signs of reactivity\u2014process hypertrophy, high phagocytic activity, and expression of genetic markers of reactivity whereas neighboring cells apparently are inactive. A period of increased intraocular pressure moves more astrocytes towards the reactive phenotype; however, some cells remain unreactive even in glaucomatous nerves.<\/jats:p>","DOI":"10.3390\/cells12172131","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:25:24Z","timestamp":1692775524000},"page":"2131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Astrocytes in the Optic Nerve Are Heterogeneous in Their Reactivity to Glaucomatous Injury"],"prefix":"10.3390","volume":"12","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"},{"name":"Department of Ophthalmology, Stanford University, 1651 Page Mill Road, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8246-3433","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"},{"name":"Department of Ophthalmology, The First Affiliated Hospital of Northwest University, Xi\u2019an 710002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"Pappas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Seifert","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Savol","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge St., Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan I.","family":"Sadreyev","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge St., Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8104-9206","authenticated-orcid":false,"given":"Tatjana C.","family":"Jakobs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear Infirmary\/Schepens Eye Research Institute, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/j.1463-5224.2007.00564.x","article-title":"Ganglion cell death in glaucoma: From mice to men","volume":"10","author":"Nickells","year":"2007","journal-title":"Vet. 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