Lycium barbarum polysaccharide relieves diabetes mellitus-induced cataract by activating Sirtuin 6

Abstract

Cataract is a vision-threatening complication of diabetes mellitus (DM), which has reached epidemic proportions globally with the rising prevalence of DM. Emerging evidence suggests Lycium barbarum polysaccharide (LBP), extracted from Lycium barbarum, is a potential medicine with protective effects on DM-induced cataract. However, the underlying molecular mechanisms involving epigenetic regulators such as Sirtuin 6 (SIRT6) require systematic investigation. In this study, we evaluated the therapeutic efficacy of LBP in the progression of DM-induced cataract in vivo and lens epithelial cells cultured under high glucose in vitro, and investigated the SIRT6-mediated autophagy-apoptosis regulatory axis. LBP significantly enhanced the transparency of the lens in DM rats, improved the pathological injury of the lens tissue, upregulated the expression of Sirt6, Beclin1, Atg5, Atg12, LC3A/B, and Bcl2; and downregulated the expression of Bax in the lens tissue of rats. The same effect was achieved by injection of AAV-SIRT6 into the anterior chamber. In vitro, the number of lens epithelial cells was increased and their arrangement was neat after LBP treatment in high glucose. Moreover, SIRT6 overexpression ameliorates high glucose-induced lens epithelial cellular damage, whereas SIRT6 knockdown exacerbates such injury. Mechanistically, LBP attenuate cellular damage by upregulating SIRT6 expression, thereby enhancing autophagy and suppressing apoptosis. Overall, LBP is identified as a protective drug that delays the occurrence and development of DM-induced cataract, and enhances autophagy, and inhibits apoptosis by activating the expression of SIRT6.

Keywords: Apoptosis; Autophagy; Diabetes mellitus–induced cataract; Lycium barbarum polysaccharide; SIRT6.