7-Ketocholesterol disturbs RPE cells phagocytosis of the outer segment of photoreceptor and induces inflammation through ERK signaling pathway.

7-Ketocholesterol (7KCh), an oxidized form of cholesterol, is present at a high level in drusen and has been believed to play a role in the pathogenesis of age-related macular degeneration (AMD). Therefore, we developed a rat model to study the direct impact of 7KCh on retina. We delivered 7KCh to the rat retina by intravitreal injection using hydroxypropyl-ß-cyclodextrin as a vehicle. We observed that 7KCh mainly deposited in the retinal pigment epithelial (RPE) cells and induced marked photoreceptor apoptosis. Transmission electron microscope examination demonstrated cytoplasmic vacuoles in RPE cells and the microvilli detached from the outer segment after 7KCh treatment. In vitro experiments also revealed that RPE cells could take up 7KCh in culture. Moreover, 7KCh up-regulated IL-1ßmRNA, TNF-αmRNA, IL-6 mRNA, and IL-1ß secretion of RPE. U0126, a MEK1/2 inhibitor, down regulated the expression of these inflammation factors. Our findings may help elucidate the potential role of 7KCh in the pathogenesis of AMD.

Activation of LXRs Reduces Oxysterol Lipotoxicity in RPE Cells by Promoting Mitochondrial Function.

Effective treatments for age-related macular degeneration (AMD), the most prevalent neurodegenerative form of blindness in older adults, are lacking. Genome-wide association studies have identified lipid metabolism and inflammation as AMD-associated pathogenic changes. Liver X receptors (LXRs) play a critical role in intracellular homeostases, such as lipid metabolism, glucose homeostasis, inflammation, and mitochondrial function. However, its specific role in AMD and its underlying molecular mechanisms remain unknown. In this study, we investigated the effects of lipotoxicity in human retinal pigmental epithelial (ARPE-19) cells and evaluated how LXRs reduce 7-ketocholesterol (7KCh) lipotoxicity in RPE cells using models, both in vivo and in vitro. A decrease in oxidative lipid accumulation was observed in mouse retinas following the activation of the LXRs; this result was also confirmed in cell experiments. At the same time, LXRs activation reduced RPE cell apoptosis induced by oxysterols. We found that oxysterols decreased the mitochondrial membrane potential in ARPE-19 cells, while LXR agonists counteracted these effects. In cultured ARPE-19 cells, activating LXRs reduced p62, mTOR, and LC3I/II levels, and the knockdown of LXRs elevated the expression of these proteins, indicating that activating LXRs could boost mitophagy. The findings of this study suggest LXR-active pharmaceuticals as a potential therapeutic target for dry AMD.

A Self-Powered Wearable Sensor for Continuous Wireless Sweat Monitoring.

Wireless wearable sweat analysis devices can monitor biomarkers at the molecular level continuously and in situ, which is highly desired for personalized health care. The miniaturization, integration, and wireless operation of sweat sensors improve the comfort and convenience while also bringing forward new challenges for power supply technology. Herein, a wireless self-powered wearable sweat analysis system (SWSAS) is designed that effectively converts the mechanical energy of human motion into electricity through hybrid nanogenerator modules (HNGMs). The HNGM shows stable output characteristics at low frequency with a current of 15 mA and a voltage of 60 V. Through real-time on-body sweat analysis powered by HNGM, the SWSAS is demonstrated to selectively monitor biomarkers (Na+ and K+ ) in sweat and wirelessly transmit the sensing data to the user interface via Bluetooth.