Exploring the potential of secondary metabolites derived from marine resources for UV-protection of the human eye/ UVISION 1.1

• Applicants: Professor Dr. Ulf Karsten; Professor Dr. Thomas Werner
• Subject Area: Biological and Biomimetic Chemistry ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Organic Molecular Chemistry - Synthesis and Characterisation ; Pharmacology ; Oceanography
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505069826

Wider research context: Mycosporines and mycosporine-like amino acids (both termed as MAAs) are secondary metabolites, which besides marine algae and invertebrates, also occur in remarkable amounts in fish ocular lenses. MAAs protect from enhanced solar radiation, as they exhibit extraordinarily high extinction coefficients in the UV range, have the capacity to counteract (UV-induced) radical formation and are photostable. Despite efforts to explore the biomedical value of these unique compounds, knowledge on interferences with mammalian antioxidant and stress response pathways is limited. Mode of action analysis is hampered by MAA availability and the absence of chemical synthesis protocols. A yet unstudied UV-sensitive, vulnerable target for MAA-mediated bioactivity is the human eye. Hypotheses: Objectives in this project are (I) the exploration of the MAA´s chemical diversity with the main focus on marine fish ocular lenses, (II) the isolation and structural analysis of new MAAs supported by bioactivity-guided fractionation using human corneal cells, (III) the upscaling of isolation methods for common MAAs to support mode of action analysis in human cells, (IV) the establishment of a synthetic route to MAA, and (V) the exploration of MAA activities on 2D and 3D cultures of corneal epithelial and endothelial cells. A targeted bioactivity analysis will be performed focusing on effects beyond UV protection, including a number of cytoprotective, inflammatory and DNA damage repair mechanisms. On the search for novel modes of action, the activity profile will be most comprehensively enlightened applying transcriptomics for selected MAAs.Methods: Ocular lenses from marine fish species will be screened for their qualitative and quantitative MAA patterns. Based on methodological experiences and developments within two previous FWF projects, the project partners will apply sophisticated isolation and structural elucidation techniques along with cell- and molecular biological approaches. In addition, a general strategy for the chemical synthesis of MAAs will be developed for the first time.Innovation: This is a unique project combining the expertise of scientists from different fields that aim to expand the knowledge on the chemical diversity of MAAs in previously unexplored marine matrices, to unravel the mode of action profile of these potent natural UV-filters beyond known target pathways on human corneal cells, and to provide a guideline for their chemical synthesis and purification.

• DFG Programme: Research Grants
• International Connection: Austria
• Cooperation Partners: Professor Dr. Markus Ganzera; Privatdozentin Dr. Johanna Gostner