{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:08:26Z","timestamp":1771931306213,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publication Funds of the Ruhr-Universit\u00e4t Bochum"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Degeneration of retinal ganglion cells (RGCs) is a hallmark of glaucoma. As RGCs are vulnerable to oxidative imbalance, anti-oxidative strategies are of significant interest as novel therapeutic targets. Fucoidans, bioactive compounds derived from algae, are known to be anti-oxidative. Hence, we investigated if fucoidans have protective effects in a retina organ culture model. Porcine explants were pre-treated with fucoidan (Fucus vesiculosus; FVs) for 0.5 h (10 or 50 \u00b5g\/mL). Afterwards, damage was induced through H2O2 (500 \u00b5M; 3 h). Four groups were investigated: control, H2O2, 10 FVs + H2O2, and 50 FVs + H2O2. RGCs, glial cells, hypoxic\/oxidative, apoptotic, and ferroptotic markers were examined by immunohistology, RT-qPCR, and a caspase assay. H2O2 led to lower RGC numbers and RBPMS expression levels while FVs prevented this degeneration. An upregulation of glial expressions and more microglia\/macrophages were observed in H2O2 samples, mitigated by FVs. Anti-oxidative genes increased during stress but normalized with FVs. Apoptotic signaling increased while GPX4 mRNA expression decreased with H2O2, both restored by FVs. Consequently, RGC loss was prevented through the attenuation of glial activation, inhibition of hypoxic\/oxidative stress, and anti-ferroptotic\/apoptotic action mediated by FVs. Advancing glaucoma research, this study emphasizes the therapeutic potential of FVs and offers new directions for future research.<\/jats:p>","DOI":"10.3390\/md24030088","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:14:44Z","timestamp":1771928084000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Sea to Sight: Fucoidan Protects Against Oxidative Damage in Porcine Retina Organ Culture"],"prefix":"10.3390","volume":"24","author":[{"given":"Leonie","family":"Deppe","sequence":"first","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7062-9918","authenticated-orcid":false,"given":"Philipp","family":"D\u00f6rschmann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center, University of Kiel, Arnold-Heller-Str. 3, Haus 25, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Burkhard","family":"Dick","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2709-1059","authenticated-orcid":false,"given":"Alexa","family":"Klettner","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center, University of Kiel, Arnold-Heller-Str. 3, Haus 25, 24105 Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-0829","authenticated-orcid":false,"given":"Stephanie C.","family":"Joachim","sequence":"additional","affiliation":[{"name":"Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/bjophthalmol-2025-egsguidelines","article-title":"European Glaucoma Society\u2014Terminology and guidelines for glaucoma, 6th Edition","volume":"109","author":"Pazos","year":"2025","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.mcna.2021.01.004","article-title":"Glaucoma","volume":"105","author":"Kang","year":"2021","journal-title":"Med. Clin. N. Am."},{"key":"ref_3","first-page":"668","article-title":"Glaucoma","volume":"93","author":"Gupta","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"ref_4","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. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/s41433-018-0042-2","article-title":"Normal tension glaucoma: Review of current understanding and mechanisms of the pathogenesis","volume":"32","author":"Killer","year":"2018","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/ceo.14043","article-title":"Normal-tension glaucoma: Current concepts and approaches\u2014A review","volume":"50","author":"Leung","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Deppe, L., Mueller-Buehl, A.M., Tsai, T., Erb, C., Dick, H.B., and Joachim, S.C. (2024). Protection against Oxidative Stress by Coenzyme Q10 in a Porcine Retinal Degeneration Model. J. Pers. Med., 14.","DOI":"10.3390\/jpm14040437"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1177\/026119291604400608","article-title":"The novel induction of retinal ganglion cell apoptosis in porcine organ culture by NMDA\u2014An opportunity for the replacement of animals in experiments","volume":"44","author":"Kuehn","year":"2016","journal-title":"Altern. Lab. Anim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12085","DOI":"10.1523\/JNEUROSCI.3200-08.2008","article-title":"Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand","volume":"28","author":"Wax","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117935","DOI":"10.1016\/j.lfs.2020.117935","article-title":"Puerarin ameliorates retinal ganglion cell damage induced by retinal ischemia\/reperfusion through inhibiting the activation of TLR4\/NLRP3 inflammasome","volume":"256","author":"Guan","year":"2020","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a041296","DOI":"10.1101\/cshperspect.a041296","article-title":"Pig Models in Retinal Research and Retinal Disease","volume":"14","author":"McCall","year":"2024","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1177\/0261192919840092","article-title":"Retinal Organ Cultures as Alternative Research Models","volume":"47","author":"Schnichels","year":"2019","journal-title":"Altern. Lab. Anim."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100880","DOI":"10.1016\/j.preteyeres.2020.100880","article-title":"Retina in a dish: Cell cultures, retinal explants and animal models for common diseases of the retina","volume":"81","author":"Schnichels","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3471","DOI":"10.1039\/c3lc50237f","article-title":"The future of the patient-specific Body-on-a-chip","volume":"13","author":"Williamson","year":"2013","journal-title":"Lab Chip"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.bbr.2017.07.040","article-title":"Vision in laboratory rodents-Tools to measure it and implications for behavioral research","volume":"352","author":"Leinonen","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1006\/exer.2002.1181","article-title":"Distribution and density of medium- and short-wavelength selective cones in the domestic pig retina","volume":"74","author":"Hendrickson","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1177\/026119291704500105","article-title":"A novel porcine ex vivo retina culture model for oxidative stress induced by H2O2","volume":"45","author":"Hurst","year":"2017","journal-title":"Altern. Lab. Anim."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.exer.2017.01.003","article-title":"Degenerative effects of cobalt-chloride treatment on neurons and microglia in a porcine retina organ culture model","volume":"155","author":"Kuehn","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mueller-Buehl, A.M., Buehner, T., Pfarrer, C., Deppe, L., Peters, L., Dick, B.H., and Joachim, S.C. (2021). Hypoxic Processes Induce Complement Activation via Classical Pathway in Porcine Neuroretinas. Cells, 10.","DOI":"10.3390\/cells10123575"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1111\/ceo.13731","article-title":"Oxidative stress-induced retinal damage is prevented by mild hypothermia in an ex vivo model of cultivated porcine retinas","volume":"48","author":"Doepper","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mueller-Buehl, A.M., Tsai, T., Hurst, J., Theiss, C., Peters, L., Hofmann, L., Herms, F., Kuehn, S., Schnichels, S., and Joachim, S.C. (2021). Reduced Retinal Degeneration in an Oxidative Stress Organ Culture Model through an iNOS-Inhibitor. Biology, 10.","DOI":"10.3390\/biology10050383"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1111\/jcmm.15091","article-title":"iNOS-inhibitor driven neuroprotection in a porcine retina organ culture model","volume":"24","author":"Hurst","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1007\/s00417-020-04854-x","article-title":"Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture","volume":"258","author":"Tsai","year":"2020","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Apostolova, E., Lukova, P., Baldzhieva, A., Katsarov, P., Nikolova, M., Iliev, I., Peychev, L., Trica, B., Oancea, F., and Delattre, C. (2020). Immunomodulatory and Anti-Inflammatory Effects of Fucoidan: A Review. Polymers, 12.","DOI":"10.3390\/polym12102338"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s10811-006-9121-z","article-title":"Antioxidant activities of sulfated polysaccharides from brown and red seaweeds","volume":"19","author":"Marques","year":"2007","journal-title":"J. Appl. Phycol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134226","DOI":"10.1016\/j.ijbiomac.2024.134226","article-title":"A comprehensive review to assess the potential, health benefits and complications of fucoidan for developing as functional ingredient and nutraceutical","volume":"277","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Obluchinskaya, E.D., Pozharitskaya, O.N., Gorshenina, E.V., Zakharov, D.V., Flisyuk, E.V., Terninko, I.I., Generalova, Y.E., and Shikov, A.N. (2023). Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk. Plants, 12.","DOI":"10.3390\/plants12122380"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Usov, A.I., Bilan, M.I., Ustyuzhanina, N.E., and Nifantiev, N.E. (2022). Fucoidans of Brown Algae: Comparison of Sulfated Polysaccharides from Fucus vesiculosus and Ascophyllum nodosum. Mar. Drugs, 20.","DOI":"10.3390\/md20100638"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1039\/D0FO02017F","article-title":"Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2","volume":"11","author":"Song","year":"2020","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41421-020-00192-8","article-title":"Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro","volume":"6","author":"Kwon","year":"2020","journal-title":"Cell Discov."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"590","DOI":"10.14336\/AD.2017.0831","article-title":"Fucoidan Protects Dopaminergic Neurons by Enhancing the Mitochondrial Function in a Rotenone-induced Rat Model of Parkinson\u2019s Disease","volume":"9","author":"Zhang","year":"2018","journal-title":"Aging Dis."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dorschmann, P., and Klettner, A. (2020). Fucoidans as Potential Therapeutics for Age-Related Macular Degeneration-Current Evidence from In Vitro Research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239272"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109469","DOI":"10.1016\/j.exer.2023.109469","article-title":"Establishment of specific age-related macular degeneration relevant gene expression panels using porcine retinal pigment epithelium for assessing fucoidan bioactivity","volume":"231","author":"Dorschmann","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Dorschmann, P., Apitz, S., Hellige, I., Neupane, S., Alban, S., Kopplin, G., Ptak, S., Frette, X., Roider, J., and Zille, M. (2021). Evaluation of the Effects of Fucoidans from Fucus Species and Laminaria hyperborea against Oxidative Stress and Iron-Dependent Cell Death. Mar. Drugs, 19.","DOI":"10.3390\/md19100557"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Summers, K.M., Bush, S.J., Wu, C., Su, A.I., Muriuki, C., Clark, E.L., Finlayson, H.A., Eory, L., Waddell, L.A., and Talbot, R. (2019). Functional Annotation of the Transcriptome of the Pig, Sus scrofa, Based Upon Network Analysis of an RNAseq Transcriptional Atlas. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.01355"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/glia.24274","article-title":"Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia","volume":"71","author":"Shih","year":"2023","journal-title":"Glia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.ophtha.2005.01.042","article-title":"Intraocular pressure-lowering effects of all commonly used glaucoma drugs: A meta-analysis of randomized clinical trials","volume":"112","author":"Webers","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tsai, T., Reinehr, S., Deppe, L., Strubbe, A., Kluge, N., Dick, H.B., and Joachim, S.C. (2024). Glaucoma Animal Models beyond Chronic IOP Increase. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020906"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3390\/molecules13081671","article-title":"Fucoidan: Structure and bioactivity","volume":"13","author":"Li","year":"2008","journal-title":"Molecules"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zayed, A., El-Aasr, M., Ibrahim, A.S., and Ulber, R. (2020). Fucoidan Characterization: Determination of Purity and Physicochemical and Chemical Properties. Mar. Drugs, 18.","DOI":"10.3390\/md18110571"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zahariev, N., Katsarov, P., Lukova, P., and Pilicheva, B. (2023). Novel Fucoidan Pharmaceutical Formulations and Their Potential Application in Oncology\u2014A Review. Polymers, 15.","DOI":"10.3390\/polym15153242"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ejmech.2015.01.002","article-title":"Sulfated glycans in inflammation","volume":"92","author":"Pomin","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1007\/s10517-019-04436-w","article-title":"Markers of Systemic Inflammation in Experimental Dyslipidemia Induced by P-407: Modulation with Fucoidan from Brown Alga Fucus evanescens","volume":"166","author":"Kuznetsova","year":"2019","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dorschmann, P., Bittkau, K.S., Neupane, S., Roider, J., Alban, S., and Klettner, A. (2019). Effects of Fucoidans from Five Different Brown Algae on Oxidative Stress and VEGF Interference in Ocular Cells. Mar. Drugs, 17.","DOI":"10.3390\/md17050258"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7518","DOI":"10.1080\/10408398.2021.1915242","article-title":"The potential of marine resources for retinal diseases: A systematic review of the molecular mechanisms","volume":"62","author":"Krueger","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.3390\/md13042447","article-title":"Seaweed polysaccharides (laminarin and fucoidan) as functional ingredients in pork meat: An evaluation of anti-oxidative potential, thermal stability and bioaccessibility","volume":"13","author":"Moroney","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lin, Z., Tan, X., Zhang, Y., Li, F., Luo, P., and Liu, H. (2020). Molecular Targets and Related Biologic Activities of Fucoidan: A Review. Mar. Drugs, 18.","DOI":"10.3390\/md18080376"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bai, X., Zhang, E., Hu, B., Liang, H., Song, S., and Ji, A. (2020). Study on Absorption Mechanism and Tissue Distribution of Fucoidan. Molecules, 25.","DOI":"10.3390\/molecules25051087"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bpobgyn.2010.10.016","article-title":"Oxidative stress","volume":"25","author":"Burton","year":"2011","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Liu, H., and Prokosch, V. (2021). Energy Metabolism in the Inner Retina in Health and Glaucoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073689"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.preteyeres.2013.07.001","article-title":"Retinal ganglion cells: Energetics, compartmentation, axonal transport, cytoskeletons and vulnerability","volume":"36","author":"Yu","year":"2013","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kowalczyk, P., Sulejczak, D., Kleczkowska, P., Bukowska-Osko, I., Kucia, M., Popiel, M., Wietrak, E., Kramkowski, K., Wrzosek, K., and Kaczynska, K. (2021). Mitochondrial Oxidative Stress-A Causative Factor and Therapeutic Target in Many Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413384"},{"key":"ref_53","first-page":"2003","article-title":"Oxidative stress, mitochondrial damage and neurodegenerative diseases","volume":"8","author":"Guo","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e15202","DOI":"10.1016\/j.heliyon.2023.e15202","article-title":"Anti-inflammatory properties of antiangiogenic fucoidan in retinal pigment epithelium cells","volume":"9","author":"Dorschmann","year":"2023","journal-title":"Heliyon"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dorschmann, P., Hunger, F., Schroth, H., Chen, S., Kopplin, G., Roider, J., and Klettner, A. (2024). Effects of Fucoidans on Activated Retinal Microglia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116018"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/j.fct.2011.04.020","article-title":"Anti-inflammatory effects of fucoidan through inhibition of NF-kappaB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells","volume":"49","author":"Park","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115195","DOI":"10.1016\/j.carbpol.2019.115195","article-title":"Fucoidan isolated from Padina commersonii inhibit LPS-induced inflammation in macrophages blocking TLR\/NF-kappaB signal pathway","volume":"224","author":"Jayawardena","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12986-019-0392-1","article-title":"Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC\/Treg induced immune tolerance and improving gut microecology","volume":"16","author":"Xue","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0092-8674(95)90070-5","article-title":"The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation","volume":"81","author":"Hsu","year":"1995","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Raffaele, S., Lombardi, M., Verderio, C., and Fumagalli, M. (2020). TNF Production and Release from Microglia via Extracellular Vesicles: Impact on Brain Functions. Cells, 9.","DOI":"10.3390\/cells9102145"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liyanage, N.M., Lee, H.G., Nagahawatta, D.P., Jayawardhana, H., Song, K.M., Choi, Y.S., Jeon, Y.J., and Kang, M.C. (2023). Fucoidan from Sargassum autumnale Inhibits Potential Inflammatory Responses via NF-kappaB and MAPK Pathway Suppression in Lipopolysaccharide-Induced RAW 264.7 Macrophages. Mar. Drugs, 21.","DOI":"10.3390\/md21070374"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.1227901","article-title":"Microglia: Scapegoat, saboteur, or something else?","volume":"339","author":"Aguzzi","year":"2013","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.pneurobio.2011.01.005","article-title":"GFAP in health and disease","volume":"93","author":"Middeldorp","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s002210000360","article-title":"An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma","volume":"132","author":"Wang","year":"2000","journal-title":"Exp. Brain Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.jphs.2014.12.019","article-title":"GFAP antibodies show protective effect on oxidatively stressed neuroretinal cells via interaction with ERP57","volume":"127","author":"Wilding","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1089\/ars.2020.8180","article-title":"Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma","volume":"35","author":"Jassim","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"456","DOI":"10.5603\/FHC.2012.0063","article-title":"HIF-1 expression in retinal ganglion cells and optic nerve axons in glaucoma","volume":"50","author":"Reszec","year":"2012","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S109","DOI":"10.3233\/JAD-201074","article-title":"Hypoxia, Oxidative Stress, and Inflammation: Three Faces of Neurodegenerative Diseases","volume":"82","author":"Merelli","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"940121","DOI":"10.1155\/2012\/940121","article-title":"Hypoxia-induced oxidative stress in health disorders","volume":"2012","author":"Pialoux","year":"2012","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_71","first-page":"330","article-title":"Fucoidan inhibits epithelial-to-mesenchymal transition via regulation of the HIF-1alpha pathway in mammary cancer cells under hypoxia","volume":"18","author":"Li","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.3390\/md13063514","article-title":"Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma","volume":"13","author":"Teng","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.bbrc.2006.05.135","article-title":"Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase","volume":"346","author":"Yang","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1111\/j.1440-1681.2009.05314.x","article-title":"Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide-activated primary microglia","volume":"37","author":"Cui","year":"2010","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Fietz, A., Corsi, F., Hurst, J., and Schnichels, S. (2023). Blue Light Damage and p53: Unravelling the Role of p53 in Oxidative-Stress-Induced Retinal Apoptosis. Antioxidants, 12.","DOI":"10.3390\/antiox12122072"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1111\/j.1460-9568.2005.04111.x","article-title":"Fucoidan inhibits cellular and neurotoxic effects of \u03b2-amyloid (A\u03b2) in rat cholinergic basal forebrain neurons","volume":"21","author":"Jhamandas","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Liu, H., Wang, J., Zhang, Q., Geng, L., Yang, Y., and Wu, N. (2020). Protective Effect of Fucoidan against MPP(+)-Induced SH-SY5Y Cells Apoptosis by Affecting the PI3K\/Akt Pathway. Mar. Drugs, 18.","DOI":"10.3390\/md18060333"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Mustafa, M., Ahmad, R., Tantry, I.Q., Ahmad, W., Siddiqui, S., Alam, M., Abbas, K., Hassan, M.I., and Habib, S. (2024). Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications. Cells, 13.","DOI":"10.3390\/cells13221838"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Vomund, S., Schafer, A., Parnham, M.J., Brune, B., and von Knethen, A. (2017). Nrf2, the Master Regulator of Anti-Oxidative Responses. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122772"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.3892\/mmr.2016.5623","article-title":"Fucoidan reduces oxidative stress by regulating the gene expression of HO-1 and SOD-1 through the Nrf2\/ERK signaling pathway in HaCaT cells","volume":"14","author":"Ryu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_82","first-page":"1341","article-title":"Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2\/HO-1\/GPX4 Activation","volume":"11","author":"Li","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.febslet.2011.10.048","article-title":"Superoxide dismutases: Ancient enzymes and new insights","volume":"586","author":"Miller","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Nojima, Y., Ito, K., Ono, H., Nakazato, T., Bono, H., Yokoyama, T., Sato, R., Suetsugu, Y., Nakamura, Y., and Yamamoto, K. (2015). Superoxide dismutases, SOD1 and SOD2, play a distinct role in the fat body during pupation in silkworm Bombyx mori. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116007"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2013.05.027","article-title":"SOD2 in mitochondrial dysfunction and neurodegeneration","volume":"62","author":"Flynn","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Singh, A., Kukreti, R., Saso, L., and Kukreti, S. (2019). Oxidative Stress: A Key Modulator in Neurodegenerative Diseases. Molecules, 24.","DOI":"10.3390\/molecules24081583"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0891-5849(02)00905-X","article-title":"Superoxide dismutase multigene family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression","volume":"33","author":"Zelko","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S1011-1344(97)00071-7","article-title":"Regulation of copper\/zinc and manganese superoxide dismutase by UVB irradiation, oxidative stress and cytokines","volume":"40","author":"Isoherranen","year":"1997","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1016\/j.biopha.2018.11.015","article-title":"Pretreated fucoidan confers neuroprotection against transient global cerebral ischemic injury in the gerbil hippocampal CA1 area via reducing of glial cell activation and oxidative stress","volume":"109","author":"Kim","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tcb.2020.12.006","article-title":"A New Paradigm in Catalase Research","volume":"31","author":"Fujiki","year":"2021","journal-title":"Trends Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Aoyama, K. (2021). Glutathione in the Brain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22095010"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Weaver, K., and Skouta, R. (2022). The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities. Biomedicines, 10.","DOI":"10.20944\/preprints202202.0316.v1"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e1800311","DOI":"10.1002\/pmic.201800311","article-title":"GPX4 at the Crossroads of Lipid Homeostasis and Ferroptosis","volume":"19","author":"Forcina","year":"2019","journal-title":"Proteomics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"16479","DOI":"10.1007\/s00210-025-04324-3","article-title":"NRF2 as a ferroptosis gatekeeper in colorectal cancer: Implications for therapy","volume":"398","author":"Alkhathami","year":"2025","journal-title":"Naunyn-Schmiedeb. Arch. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4539932","DOI":"10.1155\/2022\/4539932","article-title":"Ferroptosis-Specific Inhibitor Ferrostatin-1 Relieves H2O2-Induced Redox Imbalance in Primary Cardiomyocytes through the Nrf2\/ARE Pathway","volume":"2022","author":"Sun","year":"2022","journal-title":"Dis. Markers"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Li, M., Gao, S., Kang, M., Wu, X., An, P., Wu, X., Zheng, J., and Dang, H. (2021). The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.707959"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"133792","DOI":"10.1016\/j.ijbiomac.2024.133792","article-title":"Fucoidan alleviates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via Nrf2\/GPX4 pathway","volume":"276","author":"Wang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1097\/CM9.0000000000002533","article-title":"Acyl-CoA synthase ACSL4: An essential target in ferroptosis and fatty acid metabolism","volume":"136","author":"Ding","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zhang, L., Luo, Y.L., Xiang, Y., Bai, X.Y., Qiang, R.R., Zhang, X., Yang, Y.L., and Liu, X.L. (2024). Ferroptosis inhibitors: Past, present and future. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1407335"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e17699","DOI":"10.1111\/mec.17699","article-title":"An Evolutionary Mosaic Challenges Traditional Monitoring of a Foundation Species in a Coastal Environment-The Baltic Fucus vesiculosus","volume":"34","author":"Pereyra","year":"2025","journal-title":"Mol. Ecol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00441-017-2710-0","article-title":"HSP27 immunization reinforces AII amacrine cell and synapse damage induced by S100 in an autoimmune glaucoma model","volume":"371","author":"Reinehr","year":"2018","journal-title":"Cell Tissue Res."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/3\/88\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:17:31Z","timestamp":1771928251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/24\/3\/88"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":103,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["md24030088"],"URL":"https:\/\/doi.org\/10.3390\/md24030088","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]}}}