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The pathogenesis of DR involves different pathways, many of them exacerbated by chronic hyperglycemia, but not necessarily a direct consequence of it

elimination of excess water retention

Conformational changes of these conserved residues especially the transmission switch residues F272 6.44 and W276 6.48 have been suggested to link the extracellular agonist-binding to the cytoplasmic receptor activation and G protein-coupling for class A GPCRs (Supplementary Fig