Mass Spectrometry Imaging with Trapped Ion Mobility Spectrometry Enables Spatially Resolved Chondroitin, Dermatan, and Hyaluronan Glycosaminoglycan Oligosaccharide Analysis In Situ

Previously, spatially resolved analysis of glycosaminoglycans (GAGs), by type and sulfation state, was unobtainable. Here, we describe a mass spectrometry imaging (MSI) approach which enables the detection, identification, localization, and profiling of GAG oligosaccharides directly from retinal tissue. Through in situ treatment of tissues with relevant chondroitinase enzymes, we liberate and spatially resolve chondroitin, dermatan, and hyaluronan from disaccharides through to hexasaccharides, directly from tissue sections. We demonstrate the separation of isomeric GAG oligosaccharide ions at different histologically relevant regions using trapped ion mobility spectrometry (TIMS). This paper describes the first spatially resolved analysis of multiple GAGs and their oligosaccharide sulfation state(s) directly from tissues.