**1. Introduction**

*Laminaria hyperborea* (LH), commonly known as tangle or cuvie, belongs to the large brown seaweed family of the Laminariaceae (alias kelp). It mainly grows in the northeast Atlantic Ocean, especially around Scandinavia. LH, like all brown algal species, contains fucose-containing sulfated polysaccharides (FCSP), commonly known as fucoidan, as a cell wall component. FCSP predominantly based on sulfated L-fucose residues are defined as sulfated fucans [1]. FCSP are a very heterogeneous group of polysaccharides with strong variations in sugar composition, degree of branching and sulfation, and molecular weight. Their structure depends on different aspects, like species, harvest time, place, and extraction method [2]. This heterogeneity in structures also leads to a variety of di fferent biological activities. Sulfated fucans have been described as being able to reduce oxidative stress and inflammation, as well as being capable of interfering with vascular endothelial growth factor (VEGF) and blood lipids [3]. These properties render sulfated fucans very interesting for medical purposes, especially for the treatment of age-related macular degeneration (AMD) [4]. AMD is the main cause of blindness in the industrialized world and may cause an irreversible loss in central vision in the elderly due to the degeneration of photoreceptors within the macula lutea. This may happen in two ways: starting in the early phase with the deposition of drusen and an accumulation of lipid peroxidation products (lipofuscin), it may progress to dry AMD, where retinal pigment epithelium (RPE) degeneration is followed by a death of photoreceptors, leading to geographical atrophy of the retina as a late stage [5,6]. In wet AMD, the major growth factor of blood vessels, VEGF, is abnormally increased, leading to the growth of blood vessels under and into the retina. Followed by edema and sometimes bleeding, it leads to a disruption of the retina [5]. The pathology of AMD is based on four molecular mechanisms that increase the risk of this illness: inflammation, complement activation, oxidative burden, and disturbed VEGF generation [5,7–9]. The only therapy possibility is repeated anti-VEGF injections into the eyes of the patient [10], which slows down the pathology of wet AMD.

Because of their biological activities, FCSP are very interesting as possible new therapeutics for the treatment of AMD [3]. We showed previously that commercial sulfated fucan from *Fucus vesiculosus* reduces VEGF and the angiogenesis of RPE cells [4]. We also described the protective e ffects of *Saccharina latissima* (SL) sulfated fucan for ARPE-19 cells against oxidative stress insult; this fucan also lowered VEGF in ARPE-19 and RPE cells [11]. Other extracts from *Fucus serratus*, *Fucus distichus* subsp. *evanescens*, and *Laminaria digitata* also inhibited VEGF secretion in ARPE-19 cells [11]. The chemical structure and composition of sulfated fucan from LH has been previously described [12]. It was shown that the biological activity of LH sulfated fucan is dependent on the molecular weight and the degree of sulfation [12]. LH sulfated fucans with higher molecular weight and degree of sulfation were capable to reduce coagulation and had anti-inflammatory e ffects [12]. Stefaniak-Vidarsson et al. (2017) described the anti-proliferative e ffects of *Laminaria* sulfated fucans in activated human macrophages and showed that these sulfated fucans triggered tumor necrosis factorα and interleukins 6 and 10 [13]. However, only few reports about the activity of LH sulfated fucans can be found in the literature. Because of the described connected e ffects to molecular weight and to the high degree of sulfation, as well as the di fferent species-dependent structures and activities, we tested LH sulfated fucans additionally to the other mentioned species to find the best sulfated fucans for further AMD-relevant research.

With this study we wanted to investigate whether these LH sulfated fucans display toxic e ffects and whether they are capable of interfering with VEGF secretion and the oxidative burden in ocular cells, with a view to making an important step further to new AMD treatment possibilities. For this purpose, three pure sulfated fucans from LH were tested; these fucans di ffered only in their molecular weight and were harvested at the same time, at the same place, with the same extraction method to achieve high comparability.
