Proteomic Changes of Glycolipid Pathways in Age-Related, Diabetic, and Post-Vitrectomy Cataracts

Background: Alterations in glycolipid and glycosphingolipid pathways lead to compromised cell membranes and may be involved in cataract formation. However, the exact role of glycolipids in lens opacification is not completely understood. The aim of the current study is to investigate proteome complexity and the role of glycolipid and glycosphingolipid pathways in cataract formation. Methods: The anterior capsule and phacoemulsification (phaco) cassette contents were collected during cataract surgery from eleven participants with diabetic cataract (DC), twelve participants with age-related cataract (ARC), and seven participants with post-vitrectomy cataract (PVC). Liquid chromatography-mass spectrometry with data-independent acquisition (DIA) was used for the identification and quantification of proteins. Results: The results of this study revealed that the main significantly differentially expressed pathways in the ARC group compared to the DC and PVC groups in phaco cassette samples included the glycolipid metabolic, glycosphingolipid biosynthetic, and glycosphingolipid metabolic processes, with GLA being among the most significant proteins in the ARC group. Similarly, in the anterior capsule samples, the main significantly differentially expressed pathways in the ARC group compared to the DC and PVC groups were the glycolipid metabolic, glycosphingolipid biosynthetic, and glycosphingolipid metabolic processes, with ST3GAL5 being among the most significant proteins in the ARC group. Conclusion: Glycolipid and glycosphingolipid metabolic processes may be involved in cataract formation. ST3GAL5 may modify the cell-to-cell interaction induced by cell surface sugar chains, leading to the formation and progression of cataract. GLA, associated with the breakdown of glycolipids, may lead to cataract formation when a certain threshold is surpassed, secondary to increased glycolipid metabolism.