{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:01:05Z","timestamp":1789174865146,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zanvyl and Isabelle Krieger Fund, Baltimore, MD, USA","award":["2509\/21"],"award-info":[{"award-number":["2509\/21"]}]},{"name":"Israel Scientific Foundation","award":["2509\/21"],"award-info":[{"award-number":["2509\/21"]}]},{"name":"Claire and Amedee Maratier Institute for the Study of Blindness and Visual Disorders, Sackler Faculty of Medicine, Tel-Aviv University","award":["2509\/21"],"award-info":[{"award-number":["2509\/21"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg\/0.1 mL), intravitreal sildenafil 3 \u00b5L, or intraperitoneal sildenafil 0.1 mL (0.24 \u03bcg\/3 \u00b5L). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX\/BCL2 ratio, TGF\u03b2, and TNF\u03b1 levels in the ON and CD45 expression in WT retina. Sildenafil activated TNF\u03b1-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage.<\/jats:p>","DOI":"10.3390\/ph16040486","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T03:31:48Z","timestamp":1679887908000},"page":"486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a Rodent Microbead Model"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-7749","authenticated-orcid":false,"given":"Tal Corina","family":"Sela","sequence":"first","affiliation":[{"name":"Clalit Health Services, Tel Aviv 6209804, 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":"Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 4941492, 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":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, 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":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Sternfeld","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":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Ilguisonis","sequence":"additional","affiliation":[{"name":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Badash","sequence":"additional","affiliation":[{"name":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Geffen","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-3113","authenticated-orcid":false,"given":"Ron","family":"Ofri","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaniv","family":"BarKana","sequence":"additional","affiliation":[{"name":"The Glaucoma Innovations and Research Laboratory, The Sam Rothberg Glaucoma Center, Sheba Medical Center, Tel Hashomer 5262000, 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":"Krieger Eye Research Laboratory, Rappaport Faculty of Medicine, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"},{"name":"Department of Ophthalmology, Bnai Zion Medical Center, Haifa 3339419, Israel"},{"name":"Bruce and Ruth Faculty of Medicine, Technion, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1089\/jop.2017.0041","article-title":"Targets of Neuroprotection in Glaucoma","volume":"34","author":"He","year":"2018","journal-title":"J. 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