iNEBULA – interaction network of extracellular vesicles building universal analysis via eye tears

Discovering the secrets of diseases from tear extracellular vesicles (EVs) is well-recognized and appreciated. However, a precise understanding of the interaction network between EV populations and their biogenesis from our body requires more in-depth and systematic analysis. Researchers at Wenzhou Medical University report the biological profiles of different-size tear EV subsets from healthy individuals and the origins of EV proteins. The researchers identified about 1800 proteins and revealed the preferential differences in the biogenesis among distinct subsets. They observed that eye-related proteins that maintain retinal homeostasis and regulate inflammation are preferentially enriched in medium-size EVs (100 to 200 nm) fractions. Using universal analysis in combination with the Human Protein Atlas consensus dataset, they found the genesis of tear EV proteins with 37 tissues and 79 cell types. The proteins related to retinal neuronal cells, glial cells, and blood and immune cells are selectively enriched among EV subsets. These studies in heterogeneous tear EVs provide building blocks for future transformative precision molecular diagnostics and therapeutics.

The composition and biofunction profiles of tear EV subsets

(A) Schematic illustration of tear-derived EVs in the visual system. Exosomes originate from the endosomal pathway and are released after the fusion of multivesicular bodies (MVBs) with the plasma membrane. Microvesicles are released through plasma membrane budding. (B) Cluster patterns (left) and top 5 biological processes (right) of cluster proteins. The proteins with relatively higher abundance in the sEVs (20 to 100 nm) were included in clusters 1, 5, and 6, while clusters 2, 4, and 6 for mEVs (100 to 200 nm) and clusters 3, 4, and 5 for lEVs (200 to 450 nm). (C) Radar graph of the top 5 cellular components in the six clusters of the three EV subsets. The Z-score assessment was used for normalization (Nor.). (D) Heatmap of the relative abundance of identified EV proteins among subgroups. The scale indicates Z-score–transformed intensity. (E) Heatmap of the relative abundance of the visual system–related proteins in tear EV subsets. (F) Top 8 biological functions of the visual system–related proteins from cluster 2.