Amelioration of mouse retinal degeneration after blue LED exposure by glycyrrhizic acid-mediated inhibition of inflammation

Glycyrrhizic acid (GA) is a major component in the root and rhizomes of licorice (Glycyrrhiza glabra), which have been used as an herbal medicine, because of its anti-inflammatory activity. GA is known as an inhibitor of high-mobility group box 1 (HMGB1), which is involved in the pathogenesis of various inflammatory diseases including inner retinal neuropathy. In this study, we examined the effect of GA in a mouse model of retinal degeneration (RD), the leading cause of blindness. RD was induced by exposure to a blue light-emitting diode (LED). In functional assessment, electroretinography showed that the amplitudes of both a- and b-waves were reduced in RD mice, whereas they were significantly increased in GA-treated RD mice (P < 0.05), compared to those in non-treated RD animals. In histological assessment, GA treatment preserved the outer nuclear layer where photoreceptors reside and reduced photoreceptor cell death. GA-treated retinas showed significantly reduced expression of proinflammatory cytokines such as TNF-α, IL-6, IL-1β, CCL2 and 6, iNOS, and COX-2 (P < 0.05), compared to that in non-treated retinas. Immunohistochemistry showed that Iba-1 and GFAP expression was markedly reduced in GA-treated retinas, indicating decreased glial response and inflammation. Interestingly, HMGB1 expression was reduced in non-treated RD retinas whereas GA paradoxically increased its expression. These results demonstrate that GA preserves retinal structure and function by inhibiting inflammation in blue LED-induced RD, suggesting a potential application of GA as a medication for RD. In addition, we propose a potential retinal protective function of HMGB1 in the pathogenesis of RD.