Influence of a Very High-Molecular Weight Fucoidan from <i>Laminaria hyperborea</i> on Age-Related Macular Degeneration-Relevant Pathomechanisms in Ocular Cell Models

Fucoidans from <i>Laminaria hyperborea</i> (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models <i>in...

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Main Authors: Philipp Dörschmann, Georg Kopplin, Tabea Thalenhorst, Charlotte Seeba, Sadia Fida Ullah, Vaibhav Srivastava, Johann Roider, Alexa Klettner
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Marine Drugs
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Online Access:https://www.mdpi.com/1660-3397/23/3/101
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Summary:Fucoidans from <i>Laminaria hyperborea</i> (LH) can be antioxidative, antiangiogenic, and anti-inflammatory. In this study, a very high-molecular weight (3700 kDa) fucoidan from LH, FucBB04, was tested regarding its bioactivity in age-related macular degeneration (AMD) models <i>in vitro</i>. Primary retinal pigment epithelium (RPE) from pig eyes, human uveal melanoma cell line OMM-1, and RPE cell line ARPE-19 were used. Substituents of the extract were determined with chemical analysis. Cell viability was tested with tetrazolium assay (MTT), oxidative stress was induced by H<sub>2</sub>O<sub>2</sub> or erastin, respectively. Secreted vascular endothelial growth factor A (VEGF-A) was assessed with ELISA. Retinal pigment epithelium 65 kDa protein (RPE65) and protectin (CD59) protein expression were tested in Western blot. Cell barrier was assessed by measuring trans-epithelial electrical resistance (TEER), phagocytic ability by a fluorescence assay. Gene expression and secretion of interleukin 6 (IL-6) and interleukin 8 (IL-8) were tested in real-time PCR and ELISA. FucBB04 displayed no oxidative stress protective effects. Its effect on VEGF was inconsistent, with VEGF secretion reduced in primary RPE, but not in ARPE-19. On the other hand, Lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC)-induced IL-6 or IL-8 secretion was reduced by FucBB04, while complement inhibiting protein CD59 was not affected. In addition, FucBB04 did not influence the gene expression of IL-6 or IL-8. Visual cycle protein RPE65 expression, phagocytic ability, and barrier function were reduced by FucBB04. Very high-molecular weight fucoidan from LH shows bioactivities against AMD-related pathological pathways, but adverse effects on RPE function may limit its suitability as a therapeutic compound. Smaller high-molecular weight fucoidans are recommended for further research.
ISSN:1660-3397