Amelioration of Mouse Retinal Degeneration After Blue LED Exposure by Glycyrrhizic Acid-Mediated Inhibition of Inflammation.

Gyu Hyun Kim,Hyoun Geun Kim,Yong Soo Park,Sun-Sook Paik,In-Beom Kim

doi:10.3389/fncel.2019.00319

Gyu Hyun Kim, Hyoun Geun Kim + Show 3 more

Open Access

https://doi.org/10.3389/fncel.2019.00319

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Abstract

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.

Highlights

Retinal degeneration (RD) is a heterogeneous group of diseases characterized by the irreversible and progressive degeneration of photoreceptor cells in the retina, leading to blindness (Papermaster and Windle, 1995; Gregory-Evans and Bhattacharya, 1998; Kim G.H. et al, 2016)
In the present study, we investigated whether Glycyrrhizic acid (GA) has inhibitory effects on massive photoreceptor cell death in retinal degeneration (RD) induced by blue light-emitting diode (LED) exposure in mice via anti-inflammation
All mice-related experiments were handled according to the regulations of the Catholic Ethics Committee of the Catholic University of Korea, Seoul, which conform to the National Institute of Health (NIH) guidelines for the Care and Use of Laboratory Animals (NIH Publication No 80-23), as revised in 1996

Summary

Introduction

Retinal degeneration (RD) is a heterogeneous group of diseases characterized by the irreversible and progressive degeneration of photoreceptor cells in the retina, leading to blindness (Papermaster and Windle, 1995; Gregory-Evans and Bhattacharya, 1998; Kim G.H. et al, 2016). Glycyrrhizic Acid in Retinal Degeneration are believed to play an important role in the initiation and propagation of inflammatory responses and subsequent neuronal cell death in AMD (Karlstetter et al, 2010; Madeira et al, 2015) and in light-induced RD models (Chang et al, 2016; Kim G.H. et al, 2016). GA has inhibitory effects on inner retinal neuropathies, such as diabetic retinopathy (Chen et al, 2013; Abu El-Asrar et al, 2014), NMDA-induced injury (Sakamoto et al, 2015; Sakamoto et al, 2017), and ischemia-reperfusion injury (Dvoriantchikova et al, 2011; Liu et al, 2017), in which amacrine and ganglion cells die. The inhibitory effects of GA on outer retinal neuropathy and RD remain unclear

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