FIGURE 8.

Cartoon summary. The diagram illustrates the role of HMGB1 in the pathogenesis of blue-LED induced RD and amelioration of RD by GA. HMGB1 released from damaged photoreceptors by blue-LED exposure acts as a damp, which activates microglia. Activated microglia release proinflammatory cytokines such as TNF-α, IL-6, IL-1β, CCL2 and 6, iNOS, and COX-2, which lead to the enhancement of inflammation or cell-death signaling in photoreceptors, such as caspase-3 and RIP1/RIP3 kinases. In this pathologic process, GA acts in two modes: (1) the classical mode is to inhibit retinal inflammation by binding to released HMGB1, thereby inhibiting the activation of microglia and proinflammatory cytokine release; (2) the photoreceptor-specific mode is to protect photoreceptors by binding to nuclear HMGB1 in photoreceptors, thus leading to the stabilization of the genome against injury or inhibition of the expression of death-related genes. ONL, outer nuclear layer; OPL, outer plexiform layer; SRS, subretinal space.