# Fucoidan from Fucus vesiculosus Protects Retinal Pigment Epithelium from Lipid-Induced Damage Related to AMD

**Authors:** Femke Hacker, Johann Roider, Alexa Klettner, Philipp Dörschmann

PMC · DOI: 10.3390/md24020064 · Marine Drugs · 2026-02-02

## TL;DR

Fucoidan from Fucus vesiculosus protects retinal cells from lipid-induced damage linked to age-related macular degeneration.

## Contribution

This study demonstrates fucoidan's protective effects against lipid peroxidation in retinal pigment epithelium cells.

## Key findings

- FVs increased RPE cell viability by 12.7% compared to erastin-induced damage.
- FVs reduced VEGF and IL8 secretion, key inflammatory markers, in RPE cells.
- FVs enhanced RPE65 and GPX4 expression, supporting retinal health and lipid protection.

## Abstract

Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium (RPE) contribute to AMD development. In this study, a commercial fucoidan from Fucus vesiculosus (FVs) was tested for its activity regarding lipid-peroxidation-related effects. The human RPE cell line ARPE-19, primary porcine RPE, and RPE/choroid explants were stimulated with erastin, acting as an inducer of lipid peroxidation, and treated with fucoidan. Effects on cell viability (tetrazolium bromide (MTT) or calcein staining), vascular endothelial growth factor (VEGF) and interleukin 8 (IL8) secretion (ELISA), reactive oxygen species (ROS), protein expression (glutathione peroxidase 4 (GPX4), CD59, and retinoid isomerohydrolase (RPE65), analyzed via Western blot), and gene expression (RT-qPCR) were investigated. FVs showed protective effects against erastin-induced reduction in viability (with a 12.7% increase in viability compared to erastin), RPE65 expression (with a 4.2-fold increase compared to erastin), and GPX4 expression (with a 2.3-fold increase compared to erastin) in primary RPE. Erastin-induced VEGF secretion was attenuated by FVs in ARPE-19 and primary RPE (with an up to 1.7-fold reduction compared to erastin). Elevated IL8 levels were reduced by FV treatment in primary RPE (with a 9.1-fold reduction compared to erastin). Induced VEGF in RPE/choroid explants was reduced by FVs (with an up to 2.9-fold reduction compared to erastin), and this reduction was correlated with slight improvements in viability. In conclusion, FVs exerted protective effects against lipid-induced stress. This study reveals further effects of fucoidans against AMD-related pathologies.

## Linked entities

- **Genes:** VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], GPX4 (glutathione peroxidase 4) [NCBI Gene 2879], CD59 (CD59 molecule (CD59 blood group)) [NCBI Gene 966], RPE65 (retinoid isomerohydrolase RPE65) [NCBI Gene 6121]
- **Chemicals:** erastin (PubChem CID 11214940)
- **Diseases:** age-related macular degeneration (MONDO:0005150), AMD (MONDO:0005150)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, FLT1 (fms related receptor tyrosine kinase 1) [NCBI Gene 2321] {aka FLT, FLT-1, VEGFR-1, VEGFR1}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, RPE65 (retinoid isomerohydrolase RPE65) [NCBI Gene 6121] {aka BCO3, LCA2, RP20, mRPE65, p63, rd12}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, CYBB (cytochrome b-245 beta chain) [NCBI Gene 1536] {aka AMCBX2, CGD, CGDX, GP91-1, GP91-PHOX, GP91PHOX}, Cd59a (CD59a antigen) [NCBI Gene 12509] {aka Cd59, MAC-IP, MACIF}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, ANGPT4 (angiopoietin 4) [NCBI Gene 51378] {aka ANG3, ANG4}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, CFH (complement factor H) [NCBI Gene 3075] {aka AHUS1, AMBP1, ARMD4, ARMS1, CFHL3, FH}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, F5 (coagulation factor V) [NCBI Gene 2153] {aka FVL, PCCF, RPRGL1, THPH2, fV}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ACSL4 (acyl-CoA synthetase long chain family member 4) [NCBI Gene 2182] {aka ACS4, FACL4, LACS4, MRX63, MRX68, XLID63}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, GUSB (glucuronidase beta) [NCBI Gene 2990] {aka BG, MPS7}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, ANGPTL4 (angiopoietin like 4) [NCBI Gene 51129] {aka ARP4, FIAF, HARP, HFARP, NL2, PGAR}, CD59 (CD59 molecule (CD59 blood group)) [NCBI Gene 966] {aka 16.3A5, 1F5, EJ16, EJ30, EL32, G344}, C5 (complement C5) [NCBI Gene 727] {aka C5D, C5a, C5b, CPAMD4, ECLZB}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, GSS (glutathione synthetase) [NCBI Gene 2937] {aka CNSHA6, GSHS, HEL-S-64p, HEL-S-88n}, FLT4 (fms related receptor tyrosine kinase 4) [NCBI Gene 2324] {aka CHTD7, FLT-4, FLT41, LMPH1A, LMPHM1, PCL}, Rpe65 (retinal pigment epithelium 65) [NCBI Gene 19892] {aka 65kDa, A930029L06Rik, LCA2, Mord1, RP20, rd12}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}
- **Diseases:** AMD (MESH:D008268), atrophy (MESH:D001284), tumor (MESH:D009369), vision loss (MESH:D014786), drusen (MESH:D015593), inflammation (MESH:D007249), injury to (MESH:D014947), neurodegenerative (MESH:D019636), blindness (MESH:D001766), Hypoxia (MESH:D000860), myocarditis (MESH:D009205), geographic atrophies (MESH:D057092), toxicity (MESH:D064420), dry (MESH:D015352), metastasis (MESH:D009362), ARPE-19 (MESH:D000094024), lipid (MESH:D011017), degeneration of photoreceptors (MESH:D009410)
- **Chemicals:** lipid peroxides (MESH:D008054), streptomycin (MESH:D013307), D-PBS (MESH:C012939), polysaccharides (MESH:D011134), Fucoidan (MESH:C007789), F12 (MESH:C007782), ethylenediaminetetraacetic acid (MESH:D004492), Poly I:C (MESH:D011070), 7-ketocholesterol (MESH:C003001), NaCl (MESH:D012965), acrylamide (MESH:D020106), essential amino acid (MESH:D000601), CaCl2 (MESH:D002122), SDS (MESH:D012967), isolevuglandins (MESH:C000629758), Iron (MESH:D007501), 2',7'-dichlorofluorescein (MESH:C037631), retinoid (MESH:D012176), malondialdehyde (MESH:D008315), MTT (MESH:C070243), polyunsaturated fatty acids (MESH:D005231), Erastin (MESH:C477224), penicillin (MESH:D010406), Gibco  fetal bovine serum (-), H2O2 (MESH:D006861), phenol red (MESH:D010637), lipofuscin (MESH:D008062), dimethyl sulfoxide (MESH:D004121), fucose (MESH:D005643), Pen (MESH:C058388), ROS (MESH:D017382), PBS (MESH:D007854), Lipid (MESH:D008055), LPS (MESH:D008070), Calcein (MESH:C007740), polyphenol (MESH:D059808), taurine (MESH:D013654), L-glutamine (MESH:D005973), glutathione (MESH:D005978), CO2 (MESH:D002245)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Fucus vesiculosus (species) [taxon 49266], Phaeophyceae (brown algae, class) [taxon 2870], Laminaria hyperborea (species) [taxon 90893]
- **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), RPE — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_IQ82), ARPE-19 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0145), F8190 — Mesocricetus auratus (Golden hamster), Transformed cell line (CVCL_XK46), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006)

## Full text

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## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942446/full.md

## References

86 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942446/full.md

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Source: https://tomesphere.com/paper/PMC12942446