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

Abstract

<jats:p>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.</jats:p>

Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

“…As LPS is not associated with AMD, this in vitro model is possibly invalid to mimic AMD. Instead, Amyloid beta 1-40 oligomers-exposed non-LPS-primed RPE cell [ 53 ] may more likely mimic AMD. Another study showed that amyloid beta 1-40 oligomers at a high concentration (25 μM) lowered ARPE-19 cell viability after 24 hours of stimulation [ 38 ].…”

“…Programmed cell death (PCD) plays an important role in response to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent basic science studies also discovered novel PCD such as pyroptosis [ 53 ], necroptosis [ 88 ] and ferroptosis [ 57 ], which may contribute to the RPE cell death in AMD ( Figure 2 ). A comparison of the three novel programmed cell deaths has been listed in Table 1 .…”

“…Pyroptotic activity was firstly discovered in a Long Evans rats AMD model [ 113 ]. In 2020, a subsequent study also found pyroptosis involved in amyloid β 1-40 oligomers-induced human RPE cells, an in vitro AMD model [ 53 ]. More importantly, the observed increased expression of NLRP3 inflammasome, membrane GSDMD-N, as well as secretion of IL-1β and IL-18 could be significantly suppressed by Lycium barbarum polysaccharides (LBP) treatment, accompanied by a noticeable morphological recovery, suggesting a protective effect of LBP on an AMD in vitro model by suppressing pyroptosis [ 53 ].…”

“…In 2020, a subsequent study also found pyroptosis involved in amyloid β 1-40 oligomers-induced human RPE cells, an in vitro AMD model [ 53 ]. More importantly, the observed increased expression of NLRP3 inflammasome, membrane GSDMD-N, as well as secretion of IL-1β and IL-18 could be significantly suppressed by Lycium barbarum polysaccharides (LBP) treatment, accompanied by a noticeable morphological recovery, suggesting a protective effect of LBP on an AMD in vitro model by suppressing pyroptosis [ 53 ]. Another study [ 121 ] demonstrated that Baicalin, an active component of the radix of Scutellaria baicalensis [ 122 ], alleviated amyloid β 1-42 oligomers-induced ARPE-19 cell pyroptosis.…”

Polysaccharide-Based Nanomaterials for Ocular Drug Delivery: A Perspective

“…Many studies have suggested that certain natural polysaccharides, particularly those from plants, possess unique biological activities for the ocular system. Lycium barbarum polysaccharides have been reported to ameliorate dry eye disease, prevent oxidative damage in human trabecular meshwork cells, and preserve the function, ganglion cells, and pigment epithelium cells of the retina ( Yang et al, 2017 ; Yang M. et al, 2020 ; Chien et al, 2018 ; Lakshmanan et al, 2019 ; Liu and Zhang, 2019 ; Liu L. et al, 2020 ). Carboxymethyl Terminalia catappa polysaccharides show therapeutic effects in the cornea from blue light-emitting diodes.…”