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Given that <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB signaling is critical for neuronal survival and may regulate neurite growth, we investigated the therapeutic potential of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB signaling in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content> survival and axon regeneration. Although both <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB subunits (p65 and p50) are present in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s, p65 exists in an inactive (unphosphorylated) state when <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s are subjected to neurotoxic conditions. In this study, we used a phosphomimetic approach to generate <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> coding for an activated (phosphorylated) p65 (p65mut), then employed an adeno\u2010associated virus serotype 2 (<jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>2) to deliver the <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> into <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s. We tested whether constitutive p65mut expression prevents death and facilitates neurite outgrowth in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s subjected to transient retinal ischemia or optic nerve crush (<jats:styled-content style=\"fixed-case\">ONC<\/jats:styled-content>), two models of neurotoxicity. Our data indicate that <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s treated with <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>2\u2010p65mut displayed a significant increase in survival compared to controls in <jats:styled-content style=\"fixed-case\">ONC<\/jats:styled-content> model (77\u00a0\u00b1\u00a07% vs. 25\u00a0\u00b1\u00a03%, <jats:italic>P<\/jats:italic>\u2010value\u00a0=\u00a00.0001). We also found protective effect of modified p65 in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s of ischemic retinas (55\u00a0\u00b1\u00a012% vs. 35\u00a0\u00b1\u00a06%), but not to a statistically significant degree (<jats:italic>P<\/jats:italic>\u2010value\u00a0=\u00a00.14). We did not detect a difference in axon regeneration between experimental and control animals after <jats:styled-content style=\"fixed-case\">ONC<\/jats:styled-content>. These findings suggest that increased <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB signaling in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s attenuates retinal damage in animal models of neurodegeneration, but insignificantly impacts axon regeneration.<\/jats:p>","DOI":"10.1111\/ejn.13383","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T13:57:16Z","timestamp":1472219836000},"page":"2935-2943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Virally delivered, constitutively active <scp>NF<\/scp>\u03baB improves survival of injured retinal ganglion cells"],"prefix":"10.1111","volume":"44","author":[{"given":"Galina","family":"Dvoriantchikova","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL 33136 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Pappas","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL 33136 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueting","family":"Luo","sequence":"additional","affiliation":[{"name":"Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcio","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmara","family":"Danek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL 33136 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Pelaez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL 33136 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin K.","family":"Park","sequence":"additional","affiliation":[{"name":"Miami Project to Cure Paralysis University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine Miami FL 33136 USA"},{"name":"Department of Microbiology and Immunology University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,9,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1352"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07595.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-07-04368.1994"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1999.16.153"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802954"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-213"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02886-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1657408"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1958410"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12710"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06814.x"},{"key":"e_1_2_6_13_1","first-page":"2882","article-title":"Liposome\u2010delivered ATP effectively protects the retina against ischemia\u2010reperfusion injury","volume":"16","author":"Dvoriantchikova G.","year":"2010","journal-title":"Mol. 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