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The optic nerve is highly vulnerable to damage in neurodegenerative diseases, such as glaucoma, and there are currently no FDA-approved drugs or therapies to protect RGCs from death. Zebrafish possess remarkable neuroprotective and regenerative abilities. Here, utilizing an optic nerve transection (ONT) injury and an RNA-seq-based approach, we identify genes and pathways active in RGCs that may modulate their survival. Through pharmacological perturbation, we demonstrate that Jak\/Stat pathway activity is required for RGC survival after ONT. Furthermore, we show that immune responses directly contribute to RGC death after ONT; macrophages\/microglia are recruited to the retina and blocking neuroinflammation or depleting these cells after ONT rescues survival of RGCs. Taken together, these data support a model in which crosstalk between macrophages\/microglia and RGCs, mediated by Jak\/Stat pathway activity, regulates RGC survival after optic nerve injury.<\/jats:p>","DOI":"10.1242\/dev.199694","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T04:47:31Z","timestamp":1631767651000},"source":"Crossref","is-referenced-by-count":27,"title":["Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between Jak\/Stat signaling and innate immune responses in the zebrafish retina"],"prefix":"10.1242","volume":"149","author":[{"given":"Si","family":"Chen","sequence":"first","affiliation":[{"name":"Eye Center of Xiangya Hospital, Central South University, 410008 Changsha, Hunan, People's Republic of China"},{"name":"Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Hunan Key Laboratory of Ophthalmology, 410008 Changsha, Hunan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kira L.","family":"Lathrop","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, Pennsylvania, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-3131","authenticated-orcid":false,"given":"Takaaki","family":"Kuwajima","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Developmental Biology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-6312","authenticated-orcid":false,"given":"Jeffrey M.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Developmental Biology, Louis J. Fox Center for Vision Restoration, The University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"2022032515035746400_DEV199694C1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.preteyeres.2011.11.002","article-title":"The molecular basis of retinal ganglion cell death in glaucoma","volume":"31","author":"Almasieh","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"2022032515035746400_DEV199694C2","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1152\/physiolgenomics.00025.2005","article-title":"GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues","volume":"21","author":"Barber","year":"2005","journal-title":"Physiol. 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