*Article* **E**ff**ects of Sulfated Fucans from** *Laminaria hyperborea* **Regarding VEGF Secretion, Cell Viability, and Oxidative Stress and Correlation with Molecular Weight**

### **Philipp Dörschmann 1,\*, Georg Kopplin 2,3, Johann Roider 1 and Alexa Klettner 1**


Received: 29 August 2019; Accepted: 23 September 2019; Published: 25 September 2019

**Abstract:** Background: Sulfated fucans show interesting effects in the treatment of ocular diseases (e.g., age-related macular degeneration), depending on their chemical structure. Here, we compared three purified sulfated fucans from *Laminaria hyperborea* (LH) regarding cell viability, oxidative stress protection, and vascular endothelial growth factor (VEGF) secretion in ocular cells. Methods: High-molecular-weight sulfated fucan (Mw = 1548.6 kDa, Fuc1) was extracted with warm water and purified through ultrafiltration. Lower-molecular-weight samples (Mw = 499 kDa, Fuc2; 26.9 kDa, Fuc3) were obtained by mild acid hydrolysis of ultrapurified sulfated fucan and analyzed (SEC-MALS (Size-exclusion chromatography-Multi-Angle Light Scattering), ICP-MS, and GC). Concentrations between 1 and 100 μg/mL were tested. Cell viability was measured after 24 h (uveal melanoma cell line (OMM-1), retinal pigment epithelium (RPE) cell line ARPE-19, primary RPE cells) via MTT/MTS (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide/3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Oxidative stress protection was determined after 24 h (OMM-1, ARPE-19). VEGF secretion was analyzed via ELISA after three days (ARPE-19, RPE). Results: Fuc2 and Fuc3 were antiproliferative for OMM-1, but not for ARPE. Fuc1 protected OMM-1. VEGF secretion was lowered with all fucans except Fuc3 in ARPE-19 and RPE. The results sugges<sup>t</sup> a correlation between molecular weight and biological activity, with efficiency increasing with size. Conclusion: The LH sulfated fucan Fuc1 showed promising results regarding VEGF inhibition and protection, encouraging further medical research.

**Keywords:** fucoidan; fucan; age-related macular degeneration; VEGF; oxidative stress; *Laminaria hyperborea*; brown seaweed extracts; proliferation; molecular weight; retinal pigment epithelium
