The Effect of Lycium barbarum Polysaccharides on Pyroptosis-Associated Amyloid β1-40 Oligomers-Induced Adult Retinal Pigment Epithelium 19 Cell Damage.

Ming Yang,Kwok-Fai So,Wai Ching Lam,Amy Cheuk Yin Lo

doi:10.3390/ijms21134658

Abstract

Age-related macular degeneration (AMD) is a sight-threatening disease with limited treatment options. We investigated whether amyloid β1-40 (Aβ1-40) could cause pyroptosis and evaluated the effects of Lycium barbarum polysaccharides (LBP) on Aβ1-40 oligomers-induced retinal pigment epithelium 19 (ARPE-19) damage, which is an in vitro AMD model. Aβ1-40 oligomers verified by Western blot were added to ARPE-19 cells with or without 24 h LBP treatment. Aβ1-40 oligomers significantly decreased ARPE-19 cell viability with obvious morphological changes under light microscopy. SEM revealed swollen cells with a bubbling appearance and ruptured cell membrane, which are morphological characteristics of pyroptosis. ELISA results showed increased expression of IL-1β and IL-18, which are the final products of pyroptosis. LBP administration for 24 h had no toxic effects on ARPE-19 cells and improved cell viability and morphology while disrupting Aβ1-40 oligomerization in a dose-dependent manner. Furthermore, Aβ1-40 oligomers up-regulated the cellular immunoreactivity of pyroptosis markers including NOD-like receptors protein 3 (NLRP3), caspase-1, and membrane N-terminal cleavage product of GSDMD (GSDMD-N), which could be reversed by LBP treatment. Taken together, this study showed that LBP effectively protects the Aβ1-40 oligomers-induced pyroptotic ARPE-19 cell damages by its anti-Aβ1-40 oligomerization properties and its anti-pyroptotic effects.

Highlights

Age-related macular degeneration (AMD) is a leading cause of blindness and irreversible visual impairment in the rising aging population
There was an increased expression of membrane GSDMD-N compared with the control group (F = 42.063, p < 0.001) (Figure 5E) with an increase of the average immunofluorescence intensity (Figure 5F). All these results demonstrated that Amyloid β1-40 (Aβ1-40) activated the pyroptosis pathway in Aβ1-40 oligomers-induced retinal pigment epithelium 19 (ARPE-19) cells
Our data suggested that pyroptosis is involved in retinal pigment epithelium (RPE) cell damage upon exposure to Aβ1-40 oligomers, which is a major constituent of drusen, and possibly AMD development (Figure 6A)

Summary

Introduction

Age-related macular degeneration (AMD) is a leading cause of blindness and irreversible visual impairment in the rising aging population. Intervention of AMD is essential for preventing the aggravation of the disease [2,3,4]. The current therapies for the early stage of AMD are not satisfactory [5]. In the early stage of AMD, drusen formation and accumulation, and retinal pigment epithelium (RPE) cell damage are two prominent pathological features. Amyloid β1-40 (Aβ1-40) is often found in drusen, while amyloid β1-42 (Aβ1-42) is the major constituent of plaques, which is a prominent feature in the brains of Alzheimer’s disease patients [6,7]. Aβ1-40 oligomers have been shown to be the predominant component of drusen in the postmortem eye of a 72-year-old AMD patient [8]. Previous studies showed that exposure to Aβ1-40 oligomers resulted in a decrease in RPE cell viability [9,10]

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Conclusion