The Effect ofPolysaccharides on Pyroptosis-Associated AmyloidβOligomers-Induced Adult Retinal Pigment Epithelium 19 Cell Damage.
Int J Mol Sci. 2020 Jun 30 ;21(13). Epub 2020 Jun 30. PMID: 32629957
Age-related macular degeneration (AMD) is a sight-threatening disease with limited treatment options. We investigated whether amyloidβ(Aβ) could cause pyroptosis and evaluated the effects ofpolysaccharides (LBP) on Aβoligomers-induced retinal pigment epithelium 19 (ARPE-19) damage, which is an in vitro AMD model. Aβoligomers verified by Western blot were added to ARPE-19 cells with or without 24 h LBP treatment. Aβoligomers 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 Aβoligomerization in a dose-dependent manner. Furthermore, Aβoligomers 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 Aβoligomers-induced pyroptotic ARPE-19 cell damages by its anti-Aβoligomerization properties and its anti-pyroptotic effects.