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Glial cell activation due to increased intraocular pressure (IOP) significantly contributes to RGC death. Therefore, substances with anti-inflammatory properties could help prevent that process. This study investigated whether combining Citicoline and Coenzyme Q10 (CoQ10) can reduce glial activation in the retina and the rest of the visual pathway, potentially preventing neurodegeneration in a mouse model of unilateral laser-induced ocular hypertension (OHT). Methods: Four groups of mice were used: vehicle (n = 12), CitiQ10 (n = 12), OHT\u2013vehicle (n = 18), and OHT\u2013CitiQ10 (n = 18). The administration of Citicoline and CoQ10 was performed orally once a day, initiated 15 days prior to the laser treatment and maintained post-treatment until sacrifice (3 days for retina or 7 days for the rest of the visual pathway). The retina, dorsolateral geniculate nucleus, superior colliculus, and visual cortex (V1) were immunohistochemically stained and analyzed. Results: In the laser\u2013CitiQ10 group, the Citicoline + CoQ10 compound revealed (1) an IOP decrease at 24 h and 3 days post-laser; and (2) reduced signs of macroglial (decreased GFAP area) and microglial (soma size, arbor area, microglia number, P2RY12 expression) activation in the retina and in the rest of the visual pathway (reduced activated microglial phenotypes and lower GFAP expression). Conclusions: This study shows that oral administration of Citicoline and CoQ10 can reduce glial activation caused by increased IOP in retina and visual pathway in a mouse model of OHT, potentially protecting RGCs from OHT-induced inflammation.<\/jats:p>","DOI":"10.3390\/ph18050694","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T07:41:47Z","timestamp":1746690107000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Citicoline and Coenzyme Q10: Therapeutic Agents for Glial Activation Reduction in Ocular Hypertension"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-5225","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Matamoros","sequence":"first","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Health Research Institute of the Hospital Cl\u00ednico San Carlos (IdISSC) (ROR 014v12a39), 28040 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, Faculty of Optics and Optometry, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-2721","authenticated-orcid":false,"given":"Sara","family":"Rubio-Casado","sequence":"additional","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-7996","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Fern\u00e1ndez-Albarral","sequence":"additional","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Health Research Institute of the Hospital Cl\u00ednico San Carlos (IdISSC) (ROR 014v12a39), 28040 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, Faculty of Optics and Optometry, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7481-2536","authenticated-orcid":false,"given":"Miguel A.","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2656-4723","authenticated-orcid":false,"given":"Ana I.","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Health Research Institute of the Hospital Cl\u00ednico San Carlos (IdISSC) (ROR 014v12a39), 28040 Madrid, Spain"},{"name":"Department of Immunology, Ophthalmology and ENT, Faculty of Optics and Optometry, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5939-5551","authenticated-orcid":false,"given":"Elena","family":"Salobrar-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Ramon Castroviejo Institute for Ophthalmic Research, Complutense University of Madrid (ROR 02p0gd045), 28040 Madrid, Spain"},{"name":"Health 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Faculty of Optics and Optometry, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"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","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The Number of People with Glaucoma Worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. 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