Mass Spectrometry\nImaging with Trapped Ion Mobility\nSpectrometry Enables Spatially Resolved Chondroitin, Dermatan, and\nHyaluronan Glycosaminoglycan Oligosaccharide Analysis <i>In Situ</i>

Previously, spatially resolved analysis of glycosaminoglycans\n(GAGs),\nby type and sulfation state, was unobtainable. Here, we describe a\nmass spectrometry imaging (MSI) approach which enables the detection,\nidentification, localization, and profiling of GAG oligosaccharides\ndirectly from retinal tissue. Through <i>in situ</i> treatment\nof tissues with relevant chondroitinase enzymes, we liberate and spatially\nresolve chondroitin, dermatan, and hyaluronan from disaccharides through\nto hexasaccharides, directly from tissue sections. We demonstrate\nthe separation of isomeric GAG oligosaccharide ions at different histologically\nrelevant regions using trapped ion mobility spectrometry (TIMS). This\npaper describes the first spatially resolved analysis of multiple\nGAGs and their oligosaccharide sulfation state(s) directly from tissues.