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However, their role in visual deficits after military-relevant neurotrauma is not known. This study aims to decipher the role of CD4\u2009+\u2009Foxp3\u2009+\u2009Tregs in the development of visual deficits in a mild traumatic brain injury (mTBI) mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Seventeen-week-old genetically modified mice [C57BL\/6-Tg(Foxp3-HBEGF\/EGFP)23.2 Spar\/Mmjax] in which Foxp3\u2009+\u2009Tregs are fluorescently labeled were used in the study. Mice were subjected to a 50-psi air pulse on the left side of the head overlying the forebrain, resulting in an mTBI. A low-dose diphtheria toxin (DTx, ip, 0.05 mg\/g body weight) allowed for specific ablation of Foxp3\u2009+\u2009Treg cells. DTx treatment began 3 days before causing a blast injury and continued every 3 days to keep Tregs depleted for 30 days after the injury. Mice receiving no DTx served as Treg control, with sham-blast mice serving as additional controls for blast injury. One month following the injury, vision function was assessed by opto kinetic nystagmus and electroretinography (ERG), followed by molecular and immunohistological analysis for neuroinflammatory markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Intraperitoneal administration of DTx effectively depleted Foxp3\u2009+\u2009Treg cells in the spleen, both in sham and blast-injured mice. The blast injury resulted in a significant reduction in visual acuity and increased contrast sensitivity requirements, with these effects being exacerbated by DTx treatment. Electroretinography revealed a decrease in \u201cb\u201d wave amplitude post-blast injury, which was further reduced with DTx, though not significantly. Neuroinflammatory gene expression, including IL1\u03b2, CD86, TNF\u03b1, and CXCL10, was elevated in blast-injured mice, with DTx alone also inducing similar increases. Immunohistological analysis showed increased macroglia positive for GFAP and microglia\/macrophages positive for IBA1 expression in the retina of blast-injured mice, with further increases observed in the DTx-treated group, although these changes did not reach statistical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our studies suggest that depletion of Treg cells followed by blast injury leads to increased retinal degeneration and neuroinflammation. This highlights the continuous requirement of Foxp3\u2009+\u2009Treg cell activity to prevent neurodegeneration in mTBI. Future studies should fully explore the relationship of immunomodulatory Treg cells with neurodegeneration in blast-associated visual deficits. Therapeutics aiming to modulate Treg cells could be tested in DEREG transgenic mice after blast injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/milmed\/usaf254","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:14:20Z","timestamp":1747818860000},"page":"e2404-e2412","source":"Crossref","is-referenced-by-count":1,"title":["The Essential Role of Immunomodulatory Tregs in Visual Deficits After Military-Relevant Trauma"],"prefix":"10.1093","volume":"190","author":[{"given":"Yasaman","family":"Anvarinia","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]},{"name":"Now with Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobel A","family":"Del Mar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amritha T M","family":"Seetharaman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Shahadat","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Prislovsky","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]},{"name":"Lt. Coll Luke Weathers Jr., Memphis VA Medical Center , Memphis, TN 38104,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-7748","authenticated-orcid":false,"given":"Nawajes","family":"Mandal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]},{"name":"Lt. Coll Luke Weathers Jr., Memphis VA Medical Center , Memphis, TN 38104,","place":["United States"]},{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6664-8286","authenticated-orcid":false,"given":"Rajashekhar","family":"Gangaraju","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United States"]},{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center , Memphis, TN 38163,","place":["United 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