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Polyunsaturated fatty acid (PUFA)-derived bioactive lipids metabolized by lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) enzymes are known mediators of inflammation and neurodegeneration. However, their role in TON-related retinal pathology remains unclear. Controlled orbital impact (COI) was used to induce unilateral TON in mice with controlled velocity (2\u20133 m\/s), with the fellow eye serving as an internal control. Retina tissues were collected three days post-injury and analyzed by LC\/MS to quantify bioactive lipid metabolites from \u03c9\u22126 and \u03c9\u22123 PUFAs. Statistical analysis was performed using paired, nonparametric Wilcoxon signed-rank tests with Benjamini\u2013Hochberg false discovery rate (FDR) correction. Results showed that among 38 reliably detected metabolites, no individual lipid showed a statistically significant difference between TON and control eyes after FDR correction (q &lt; 0.05). However, both individual and pathway-level analysis revealed consistent trends toward increased expression of LOX- and CYP-derived metabolites across FDA PUFA substrates, including arachidonic acid (AA), linoleic acid (LA), and docosahexaenoic acid (DHA). These findings support further investigation into lipid-mediated inflammation in TON and its potential as a therapeutic target, particularly through expanding both the sample size and the post-TON time periods.<\/jats:p>","DOI":"10.3390\/biom15101450","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:34:15Z","timestamp":1760452455000},"page":"1450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alterations of Bioactive Lipid Profiles in the Retina Following Traumatic Optic Neuropathy in Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6747-0961","authenticated-orcid":false,"given":"Min Young","family":"Kim","sequence":"first","affiliation":[{"name":"Eye Research Center and Foundational Medical Studies, Oakland University William Beaumont School of Medicine (OUWB-SOM), Rochester, MI 48309, USA"},{"name":"Eye Research Institute, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6441-3771","authenticated-orcid":false,"given":"Nandini","family":"Koneru","sequence":"additional","affiliation":[{"name":"Eye Research Center and Foundational Medical Studies, Oakland University William Beaumont School of Medicine (OUWB-SOM), Rochester, MI 48309, USA"},{"name":"Eye Research Institute, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gieth","family":"Alahdab","sequence":"additional","affiliation":[{"name":"Eye Research Center and Foundational Medical Studies, Oakland University William Beaumont School of Medicine (OUWB-SOM), Rochester, MI 48309, USA"},{"name":"Eye Research Institute, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8399-5036","authenticated-orcid":false,"given":"Michael","family":"Risner","sequence":"additional","affiliation":[{"name":"Eye Research Center and Foundational Medical Studies, Oakland University William Beaumont School of Medicine (OUWB-SOM), Rochester, MI 48309, USA"},{"name":"Eye Research Institute, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8480-6252","authenticated-orcid":false,"given":"Ahmed S.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"},{"name":"Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-791X","authenticated-orcid":false,"given":"Krishna Rao","family":"Maddipati","sequence":"additional","affiliation":[{"name":"Bioactive Lipids Research Program, Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48202, USA"},{"name":"Lipidomics Core Facility, Wayne State University School of Medicine, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5362-7972","authenticated-orcid":false,"given":"Mohamed","family":"Al-Shabrawey","sequence":"additional","affiliation":[{"name":"Eye Research Center and Foundational Medical Studies, Oakland University William Beaumont School of Medicine (OUWB-SOM), Rochester, MI 48309, USA"},{"name":"Eye Research Institute, Oakland University, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","first-page":"73","article-title":"Post-Traumatic Visual Loss","volume":"5","author":"Atkins","year":"2008","journal-title":"Rev. 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