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EY031042"],"award-info":[{"award-number":["NIH R01 EY031042"]}]},{"name":"BrightFocus grant","award":["VA I01RX002806"],"award-info":[{"award-number":["VA I01RX002806"]}]},{"name":"BrightFocus grant","award":["VA I21RX001924"],"award-info":[{"award-number":["VA I21RX001924"]}]},{"name":"BrightFocus grant","award":["VARR&D C9246C"],"award-info":[{"award-number":["VARR&D C9246C"]}]},{"name":"BrightFocus grant","award":["NIH P30EY06360"],"award-info":[{"award-number":["NIH P30EY06360"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["G2020286"],"award-info":[{"award-number":["G2020286"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["G2022012S"],"award-info":[{"award-number":["G2022012S"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["NIH R01EY028859"],"award-info":[{"award-number":["NIH R01EY028859"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["NIH R01EY021592"],"award-info":[{"award-number":["NIH R01EY021592"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["NIH R01EY028450"],"award-info":[{"award-number":["NIH R01EY028450"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["NIH R01 EY031042"],"award-info":[{"award-number":["NIH R01 EY031042"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["VA I01RX002806"],"award-info":[{"award-number":["VA I01RX002806"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["VA I21RX001924"],"award-info":[{"award-number":["VA I21RX001924"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["VARR&D C9246C"],"award-info":[{"award-number":["VARR&D C9246C"]}]},{"name":"The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University","award":["NIH P30EY06360"],"award-info":[{"award-number":["NIH P30EY06360"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Purpose: The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model of retinal ganglion cell (RGC) death. Methods: C57BL\/6J mice were injected intraperitoneally (i.p.) three times per week with TUDCA (500 mg\/kg) for two weeks, after which unilateral ONC was performed. A control cohort was identically treated with a drug vehicle (phosphate buffered saline; PBS). A separate cohort did not undergo any injections or surgeries (this was termed the \u201cNa\u00efve\u201d group). Pattern electroretinography (PERG) was recorded 3 days after ONC. Retinas were harvested for whole-mount immunofluorescence staining with an antibody against RGC marker Brn3a and imaged by fluorescent confocal microscopy. Apoptotic cells in the ganglion cell layer (GCL) were detected by Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (TUNEL) performed on fixed retina sections. Glial fibrillary acidic protein (GFAP) immunostaining on fixed retina sections was conducted to detect the activation of M\u00fcller cells. Total RNA was extracted from retinas and expression of interleukin (IL)-1\u03b2, IL-6, tumor necrosis factor (TNF)-\u03b1, and IL-10 was determined by digital droplet PCR (ddPCR). Results: TUDCA treatment preserved visual function as assessed by PERG. P1 and N2 amplitudes from the PBS-treated ONC group were significantly diminished compared to those of the Na\u00efve group (p &lt; 0.001). TUDCA treatment prevented this diminution. The amplitudes of P1 and N2 in the TUDCA-treated ONC group were statistically indistinguishable from those of the Na\u00efve group and were higher than the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, P1: 6.99 \u00b1 0.89 \u00b5V vs. 3.60 \u00b1 0.69 \u00b5V, p &lt; 0.01; N2: \u22129.30 (IQR: \u221213.43\u2013\u22126.44) \u00b5V vs. \u22124.47 (IQR: \u221210.26\u2013\u22122.17) \u00b5V). TUDCA treatment preserved RGCs. The ONC-vehicle-only group had 25% fewer RGCs (Brn3a-positive cells) than Na\u00efve eyes (p &lt; 0.0001). TUDCA treatment nearly completely prevented this loss, preserving all but 7.7% of the RGCs, and the number of RGCs in the TUDCA-treated ONC group was significantly higher than in the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, 1738.00 \u00b1 14.43 cells per field vs. 1454.00 \u00b1 6.55 cells per field, p &lt; 0.0001). The number of TUNEL-positive cells in the GCL (Na\u00efve vs. PBS+ONC group: 1.00 (IQR: 0.00\u20132.00) % vs. 37.00 (IQR: 8.50\u201348.50) %, p &lt; 0.05) and GFAP-positive fibers transversing retina sections (Na\u00efve vs. PBS+ONC group: 33.00 \u00b1 1.15 vs. 185.70 \u00b1 42.37 fibers\/retina, p &lt; 0.05), and the expression of IL-6, TNF-\u03b1 were significantly greater in the PBS-treated ONC group compared to that of the Na\u00efve group (Na\u00efve vs. PBS+ONC group, IL-6: 0.07 (IQR: 0.06\u20130.31) vs. 0.99 (IQR: 0.56\u20131.47), p &lt; 0.05, TNF-\u03b1: 0.19 \u00b1 0.069 vs. 1.39 \u00b1 0.23; p &lt; 0.01), an increase not observed with TUDCA treatment. Conclusions: Systemic TUDCA treatment significantly preserved RGC function and survival in the mouse ONC model of RGC damage. TUDCA treatment prevented RGC apoptosis, M\u00fcller glial cell activation, and retinal expression of several inflammatory cytokines. These data suggest that TUDCA is a promising therapeutic candidate for preserving RGC numbers and function.<\/jats:p>","DOI":"10.3390\/ph18040569","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T07:42:01Z","timestamp":1744616521000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tauroursodeoxycholic Acid Protects Retinal Ganglion Cells and Reduces Inflammation in Mice Following Optic Nerve Crush"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-1863","authenticated-orcid":false,"given":"Nan","family":"Zhang","sequence":"first","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"},{"name":"Department of Ophthalmology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-4914","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"},{"name":"Department of Ophthalmology, Second Xiangya Hospital of Central South University, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1366-5963","authenticated-orcid":false,"given":"Micah A.","family":"Chrenek","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"},{"name":"Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preston E.","family":"Girardot","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana T.","family":"Sellers","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-4416","authenticated-orcid":false,"given":"Eldon E.","family":"Geisert","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-9897","authenticated-orcid":false,"given":"John M.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5875-492X","authenticated-orcid":false,"given":"Jeffrey H.","family":"Boatright","sequence":"additional","affiliation":[{"name":"Atlanta Veterans Administration Center for Visual and Cognitive Rehabilitation, Decatur, GA 30033, USA"},{"name":"Department of Ophthalmology, School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","first-page":"668","article-title":"Glaucoma","volume":"93","author":"Gupta","year":"2016","journal-title":"Am. 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