Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

Abstract

Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina.

Correcting for sparsity and interdependence in glycomics by accounting for glycan biosynthesis

“…In addition, a later study also found significant depletion of multiple bi-GlcNAc core 2 and I-branched structures 37 . Also consistent with the decrease in bi-GlcNAc core-2 structures in gastric cancer, low expression of B3GNT3 in stomach cancer is significantly associated with decreased overall survival 38 . B3GNT3 is necessary for adding the second GlcNac to core 2 structure 39 and therefore upstream of all significantly depleted structures (Fig.…”

“…To explore the broad applicability of GlyCompare, we used our method to calculate substructure abundance for mucin-type O-glycans 37 (Fig. 7 ), glycolipids 38 (Supplementary Fig. 12 ), and site-specific compositional N-glycosylation 22 (Supplementary Fig.…”

Biophysical analysis of the plant-specific GIPC sphingolipids reveals multiple modes of membrane regulation

“…Plant GIPCs are structurally homologous to the animal gangliosides that are absent in plants. Gangliosides are acidic glycolipids containing sialic acid in their polar head that play an important role in immunity, signal transduction in the PM that essential for brain, and retinal functions in animal cells ( 68 , 69 ). It is possible that polyglycosylated GIPCs have a similar role to gangliosides.…”

Purification, characterization and influence on membrane properties of the plant-specific sphingolipids GIPC

“…Plant GIPCs are structurally homologous to the animal gangliosides that are absent in plants. Gangliosides are acidic glycolipids containing sialic acid in their polar head that play an important role in immunity, signal transduction in the PM that essential for brain and retinal functions in animal cells (Sonnino & Prinetti, 2010) (Sibille et al, 2016). It is possible that polyglycosylated GIPCs have a similar role to gangliosides.…”