Marine-Derived Fucoidan Modulates Pathways Associated with Age-Related Macular Degeneration in Cellular and Zebrafish Models.

Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms.