bims-mideyd 2024-11-10 papers

Heliyon. 2024 Oct 30. 10(20): e38151

Cigarette smoke extract induces ferroptosis in human retinal pigment epithelial cells.

Long Zhao, Ping Wu, Jing Lu, Yuxia He, Qinxin Shu, Fuying Pan, Hao Xie, Xing Wang, Huan Ju, Yong Du, Hui Peng.

Background: Age-related macular degeneration (AMD) is a common blindness diseases. Retinal pigment epithelium (RPE) dysfunction due to smoking is an essential environmental factor in the pathogenesis of AMD. Ferroptosis is a novel type of iron-dependent programmed cell death (PCD). However, the relationship between cigarette smoke extract (CSE)-induced RPE damage and ferroptosis remains unclear.
Methods: In our study, we extracted CSE using a modified device to explore the optimal concentration of CSE, and observed the expression of proteins and molecules after CSE exposure for ARPE-19 cells by protein immunoblotting and assay kits for iron ions and mitochondrial membrane potential (MMP). At the same time, CSE was injected into the vitreous cavity of mice with a microsyringe for AMD modeling to observe the morphology of the retina-RPE-choroid complex and the differences expression of proteins. In addition, the protective effects of ferroptosis inhibitors on CSE-induced RPE cell damage were also investigated by in vivo and in vitro experiments.
Results: In this study, we observed that CSE induced cellular damage in a human retinal pigment epithelial cell line (ARPE-19), resulting in ferrous ion (Fe2+) accumulation, an increas in reactive oxygen species (ROS) and lipid peroxidation (LP), a reduction in GSH levels, and the inhibition of Gpx4 expression. In addition, transmission electron microscopy (TEM) of in vivo and in vitro samples showed that after exposure to CSE, the mitochondria of RPE cells were wrinkled, the membrane density was increased, and the number of cristae decreased or cristae were not observed.
Conclusions: The results of this study indicate that the ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) protect RPE cells from CSE-induced ferroptosis, and this evidence paves the way for AMD studies.

Keywords: Age-related macular degeneration; Cigarette smoke extract; Ferroptosis; Retinal pigment epithelium

DOI: https://doi.org/10.1016/j.heliyon.2024.e38151

Food Sci Biotechnol. 2024 Dec;33(15): 3607-3616

The protective effect of 20(S)-ginsenoside Rg3 on the human retinal pigment epithelial cells against hydrogen peroxide-induced oxidative stress.

Bo Kyeong Kim, Ki-Uk Kim, Jisu Kim, Hyunjun Jang, Hyeyoung Min.

Ginsenosides, constituting 2-3% of Panax ginseng Meyer, are noteworthy for their anticancer and antioxidant effects. Despite demonstrating promise in various diseases, their specific impact on age-related macular degeneration (AMD) remains unclear. This research investigates whether ginsenosides can inhibit the progression of dry AMD and explores the mechanisms by which they influence apoptosis, providing insight into their regulatory role in programmed cell death. Human retinal pigment epithelial (ARPE-19) cells were pre-treated with ginsenosides, followed by induction of oxidative stress using hydrogen peroxide. Pre-treatment with 20(S)-ginsenoside Rg3 significantly increased cell viability and reduced apoptotic markers, including Annexin V, Bax, Bim S, cleaved caspase 3, cleaved caspase 9, and cleaved PARP. Furthermore, 20(S)-ginsenoside Rg3 effectively diminished the activation of the ERK and NF-κB signaling pathways. 20(S)-ginsenoside Rg3 could be a good prevention for AMD by modulating apoptosis, offering valuable therapeutic insights for AMD.

Keywords: 20(S)-ginsenoside Rg3; Age-related macular degeneration (AMD); Apoptosis; Human retinal pigment epithelial cell; Oxidative stress

DOI: https://doi.org/10.1007/s10068-024-01617-w

Free Radic Biol Med. 2024 Nov 02. pii: S0891-5849(24)01015-3. [Epub ahead of print]225 833-845

The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium.

Peng Shang, Helena Ambrosino, Johnson Hoang, Zhaohui Geng, Xiaoyu Zhu, Shichen Shen, Mark Eminhizer, Elise Hong, Ming Zhang, Jun Qu, Jianhai Du, Sandra R Montezuma, James R Dutton, Deborah A Ferrington.

Age-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype. Chronic CSE altered the metabolic profile in both LR and HR iPSC-RPE and caused a dose-dependent reduction in mitochondrial function despite an increase in mitochondrial content. Notably, cells with the HR CFH SNP showed a greater reduction in maximal respiration and ATP production. Significant genotype-dependent changes in the proteome were observed for HR RPE at baseline (cytoskeleton, MAPK signaling) and after CSE exposure, where a less robust upregulation of the antioxidants and significant downregulation in proteins involved in nucleic acid metabolism and membrane trafficking were noted compared to LR cells. In LR cells, uniquely upregulated proteins were involved in lipid metabolism and chemical detoxification. These genotype-dependent differences at baseline and in response to chronic CSE exposure suggest a broader role for CFH in modulating the response to oxidative stress in RPE and provides insight into the interaction between environmental and genetic factors in AMD pathogenesis.

Keywords: Bioinformatics; Cigarette smoke extract; Metabolomics; Proteomics; iPSC-RPE

DOI: https://doi.org/10.1016/j.freeradbiomed.2024.10.307