{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:00:50Z","timestamp":1789174850675,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recanati Foundation Herman Schauder Fund"},{"name":"Zanvyl and Isabelle Krieger Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study evaluated the potential neuroprotective effect of azithromycin (AZ) intraperitoneal injections in male C57Bl\/6 (wild type, WT) and female NOD scid gamma (NSG) mice subjected to optic nerve crush (ONC) as a model for optic neuropathy. Histologically, reduced apoptosis and improved retinal ganglion cell (RGC) preservation were noted in the AZ-treated mice as shown by TUNEL staining\u2014in the WT mice more than in the NSG mice. The increased microglial activation following ONC was reduced with the AZ treatment. In the molecular analysis of WT and NSG mice, similar trends were detected regarding apoptosis, as well as stress-related and inflammatory markers examining BCL2-associated X (Bax), heme oxygenase 1 (Ho-1), interleukin 1 beta (Il1\u03b2), superoxide dismutase 1 (Sod1), and nuclear factor-kappa B (Nfkb) levels. In the optic nerve, AZ increased the levels of expression of Sod1 and Nfkb only in the WT mice and decreased them in the NSG mice. In the retinas of the WT and NSG mice, the Bax and Ho-1 levels of expression decreased following the AZ treatment, while the Sod1 and Nfkb expression decreased only in the WT mice, and remained stable near the baseline in the NSG mice. Il1\u03b2 remained at the baseline in WT mice while it decreased towards the baseline in AZ-treated NSG mice. The neuroprotective effects demonstrated by the reduced RGC apoptosis in AZ-treated WT mice retinae, and in the optic nerves as stress-related and inflammatory gene expression increase. This did not occur in the immunodeficient NSG mice. AZ modulated the inflammatory reaction and microglial activation. The lack of an effect in NSG mice supports the assumption that AZ acts by immunomodulation, which is known to play a role in ONC damage. These findings have implications for the development and repurposing of drugs to preserve RGCs after acute optic neuropathies.<\/jats:p>","DOI":"10.3390\/ijms231911872","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neuroprotective Effect of Azithromycin Following Induction of Optic Nerve Crush in Wild Type and Immunodeficient Mice"],"prefix":"10.3390","volume":"23","author":[{"given":"Ofira","family":"Zloto","sequence":"first","affiliation":[{"name":"Goldschlager Eye Institute, Sheba Medical Center, Ramat Gan 5262000, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-5253","authenticated-orcid":false,"given":"Alon","family":"Zahavi","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Department of Ophthalmology, Rabin Medical Center\u2014Beilinson Hospital, Petach Tikva 4941492, Israel"},{"name":"The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1064-7997","authenticated-orcid":false,"given":"Stephen","family":"Richard","sequence":"additional","affiliation":[{"name":"The Krieger Eye Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moran","family":"Friedman-Gohas","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1724-3407","authenticated-orcid":false,"given":"Shirel","family":"Weiss","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-1873","authenticated-orcid":false,"given":"Nitza","family":"Goldenberg-Cohen","sequence":"additional","affiliation":[{"name":"The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petach Tikva 4941492, Israel"},{"name":"The Krieger Eye Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel"},{"name":"Department of Ophthalmology, Bnai Zion Medical Center, Haifa 3339419, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1056\/NEJMra1413352","article-title":"Ischemic optic neuropathies","volume":"372","author":"Biousse","year":"2015","journal-title":"N. 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