RAGE signaling represents an ongoing source of vascular inflammation in diabetes [171], with its role made more complex through interaction with the increased production of its ligand S100B [168] and the secreted form of the nuclear chaperone high mobility group box-1 (HMGB1) [172] protein that has been implicated in inflammation and vascular injury in DR [173,174,175] (see the review by Steinle [173]). The gene discussed is HMGB1; the disease is diabetes mellitus.