<p>Meibum, secreted from the meibomian glands, is the main contributor to the outermost protective layer of the human tear film, i.e. the tear film lipid layer (TFLL). This interesting biofilm features a complex composition of lipid species and contributes to the sustenance of ocular surface health. Alterations in the composition of meibum and the TFLL have been linked to the development of ocular diseases and several lipid species have been identified as potential biomarkers for disease progression. Despite the successes achieved through state-of-the-art lipidomic profiling techniques, the research community has indicated that there is a need for isotopically labeled reference standards from several unique tear film lipid classes. To contribute to such advances, we herein set out to synthesize representative deuterium-labeled human tear film lipid standards for lipid classes where standards are currently unavailable. These lipid classes were identified as the <i>O</i>-acyl-ω-hydroxy fatty acids, type I-St and type II diesters. In addition to describing the synthesis of such lipid standards with high isotopic purity, we herein discuss the detailed structural characterization of deuterated standards and lessons learned from an early-stage assessment of their suitability as standards for lipidomic profiling of human meibum.</p>

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Synthesis and structural characterization of deuterium-labeled human tear film lipids and initial assessment of their potential as standards for lipidomic profiling work

  • Henrik Stubb,
  • Ioana Stefan,
  • Minna Holopainen,
  • Andrew H. House,
  • Hanna Ruhanen,
  • Alexandra Robciuc,
  • Sami Heikkinen,
  • Jukka Moilanen,
  • Reijo Käkelä,
  • Filip S. Ekholm

摘要

Meibum, secreted from the meibomian glands, is the main contributor to the outermost protective layer of the human tear film, i.e. the tear film lipid layer (TFLL). This interesting biofilm features a complex composition of lipid species and contributes to the sustenance of ocular surface health. Alterations in the composition of meibum and the TFLL have been linked to the development of ocular diseases and several lipid species have been identified as potential biomarkers for disease progression. Despite the successes achieved through state-of-the-art lipidomic profiling techniques, the research community has indicated that there is a need for isotopically labeled reference standards from several unique tear film lipid classes. To contribute to such advances, we herein set out to synthesize representative deuterium-labeled human tear film lipid standards for lipid classes where standards are currently unavailable. These lipid classes were identified as the O-acyl-ω-hydroxy fatty acids, type I-St and type II diesters. In addition to describing the synthesis of such lipid standards with high isotopic purity, we herein discuss the detailed structural characterization of deuterated standards and lessons learned from an early-stage assessment of their suitability as standards for lipidomic profiling of human meibum.