Fucoxanthin protects retinal ganglion cells and promotes parkin-mediated mitophagy against glutamate excitotoxicity

Abstract

Objective To clarify whether fucoxanthin plays a protective role and regulates parkin-mediated mitophagy on retinal ganglion cells (RGCs) against glutamate excitotoxicity. MethodsThe excitotoxicity model of primary RGCs was carried out with glutamate. Mitochondrial membrane potential was measured by JC-1 kit (Abcam, USA). The apoptotic rate and cytotoxicity were detected by Hoechst staining and lactate dehydrogenase (LDH) kit (Takara, Japan). Mitochondria was assessed by MitoTracker staining and confocal microscopy. The mRNA levels and protein expression levels of Bax, Bcl-2, parkin, optineurin, LC3, and LAMP1 in RGCs were analyzed by quantitative PCR and immunoblotting. Finally, the mitochondrial health score and mitophagy were assessed by transmission electron microscopy. ResultsFucoxanthin increased the mitochondrial membrane potential of RGCs, reduced cytotoxicity, and decreased apoptosis in RGCs under glutamate excitotoxicity. It also enhanced expression levels of parkin, optineurin, and LAMP1, and upgraded the ratio of LC3-II to LC3-I. Meanwhile, fucoxanthin increased LC3 and MitoTracker co-localization staining. In addition, up-regulated mitochondrial health score, and the number of autophagosomes and mitophagosomes were observed in fucoxanthin-treated RGCs under glutamate excitotoxicity. ConclusionFucoxanthin may exert its neuroprotective effect on RGCs via promoting parkin-mediated mitophagy under glutamate excitotoxicity. The neuroprotective effect of fucoxanthin in glaucomatous neurodegeneration and ocular diseases characterized by impaired mitophagy warrants further investigation.

Mitochondrial protective potential of fucoxanthin in brain disorders

“…The direct role of fucoxanthin on mitochondrial quality control in the PD brain is unknown. Lian et al showed that treatment with fucoxanthin increased the ratio of LC3-II to LC3-I, the protein level of Parkin, and the number of autophagosomes and mitophagosomes in retinal ganglion cells challenged with excitotoxicity, (75) suggesting that fucoxanthin has a role in regulating mitophagy. Those authors further showed that fucoxanthin prevented the loss of mitochondrial membrane potential during excitotoxicity and helped protect from apoptotic death by lowering Bax and increasing Bcl-2.…”

The Role of Mitophagy in Glaucomatous Neurodegeneration

“…In a rat glaucoma model, adeno-associated virus 2-PARKIN (AAV2-PARKIN), which was used to overexpress PARKIN, led to a significant decrease in RGC loss and partial restoration of mitophagy levels under elevated IOP conditions, suggesting that clearance of impaired mitochondria through mitophagy is directly linked to better RGC survival [22]. Fucoxanthin, a carotenoid of the xanthophyll family with antioxidant and anti-inflammatory properties, also exerts protective effects on RGCs by enhancing PARKIN-mediated mitophagy under glutamate excitotoxicity [231]. Interestingly, a chronic ocular hypertension rat glaucoma model showed that during short-term IOP elevations, fucoxanthin decreases PARKIN expression and reduces the number of mitophagosomes and autophagosomes to prevent excessive damage caused by unrestrained mitophagy, while during long-term IOP elevations, fucoxanthin protects RGCs, improves mitochondrial health, increases PARKIN expression and enhances the PARKIN-mediated mitophagy pathway [232].A recent study by Zhuang et al [233] showed that the small natural molecule S3 derived from diterpenoids could protect RGCs by enhancing PARKIN-mediated mitophagy under NMDA-induced excitotoxicity.…”

Fucoxanthin protects retinal ganglion cells and promotes parkin-mediated mitophagy against glutamate excitotoxicity: Erratum

“…The correspondence was incorrectly listed in this article [1]. It should have been listed as follows:…”