Comparison of Fucoidans from Saccharina latissima Regarding Age-Related Macular Degeneration Relevant Pathomechanisms in Retinal Pigment Epithelium

Abstract

Fucoidans from brown algae are described as anti-inflammatory, antioxidative, and antiangiogenic. We tested two Saccharina latissima fucoidans (SL-FRO and SL-NOR) regarding their potential biological effects against age-related macular degeneration (AMD). Primary porcine retinal pigment epithelium (RPE), human RPE cell line ARPE-19, and human uveal melanoma cell line OMM-1 were used. Cell survival was assessed in tetrazolium assay (MTT). Oxidative stress assays were induced with erastin or H2O2. Supernatants were harvested to assess secreted vascular endothelial growth factor A (VEGF-A) in ELISA. Barrier function was assessed by measurement of trans-epithelial electrical resistance (TEER). Protectin (CD59) and retinal pigment epithelium-specific 65 kDa protein (RPE65) were evaluated in western blot. Polymorphonuclear elastase and complement inhibition assays were performed. Phagocytosis of photoreceptor outer segments was tested in a fluorescence assay. Secretion and expression of proinflammatory cytokines were assessed with ELISA and real-time PCR. Fucoidans were chemically analyzed. Neither toxic nor antioxidative effects were detected in ARPE-19 or OMM-1. Interleukin 8 gene expression was slightly reduced by SL-NOR but induced by SL-FRO in RPE. VEGF secretion was reduced in ARPE-19 by SL-FRO and in RPE by both fucoidans. Polyinosinic:polycytidylic acid induced interleukin 6 and interleukin 8 secretion was reduced by both fucoidans in RPE. CD59 expression was positively influenced by fucoidans, and they exhibited a complement and elastase inhibitory effect in cell-free assay. RPE65 expression was reduced by SL-NOR in RPE. Barrier function of RPE was transiently reduced. Phagocytosis ability was slightly reduced by both fucoidans in primary RPE but not in ARPE-19. Fucoidans from Saccharina latissima, especially SL-FRO, are promising agents against AMD, as they reduce angiogenic cytokines and show anti-inflammatory and complement inhibiting properties; however, potential effects on gene expression and RPE functions need to be considered for further research.

Effects of Fucoidans on Activated Retinal Microglia

“…In addition, additional aspects of microglia activation would be of interest, such as cytoplasmic makers, further pro-inflammatory gene expression, or additional interleukin or chemokine secretion. For example, it would be of interest whether the effect would be similar if a Toll-like-receptor (TLR3) antagonist were used, as we have previously shown that several fucoidans can reduce inflammatory activation of RPE cells after TLR-3 activation [ 30 , 52 ]. Also, different timelines of activation and concentrations of fucoidan would be of interest.…”

Molecular Mechanisms of Retinal Degeneration and How to Avoid It

“…AMD is a progressive disease that can lead to vision loss in people over the age of 50, thus gaining more and more relevance in aging societies. Dörschmann and the Klettner group [5,6] provided new evidence on how a group of plant polysaccharides, fucoidans, are capable of alleviating the effects of AMD. In their elegant back-to-back studies, they analyzed the true potential of fucoidans in retinal medicine.…”