Role of nuclear factor (erythroid-derived 2)-like 2 in the age-resistant properties of the glaucoma trabecular meshwork

Oxidative Medicine and Cellular Longevity

et al. 2022

Choline is a precursor of the major neurotransmitter acetylcholine and has been demonstrated beneficial in diverse models of cardiovascular disease. Here, we sought to verify that choline protects the heart from DOX-induced cardiotoxicity and the underlying mechanisms. The results showed that DOX treatment decreased left ventricular ejection fraction and fractional shortening and increased serum cardiac markers and myocardial fibrosis, which were alleviated by cotreatment with choline. DOX-induced cardiotoxicity was accompanied by increases in oxidative stress, inflammation, and apoptosis, which were rectified by choline cotreatment. Levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase-1 (HO-1), which are antioxidant markers, were lowered by DOX and upregulated by choline. Moreover, DOX significantly decreased serum acetylcholine levels and the high-frequency component of heart rate variability and increased serum norepinephrine levels and the low-frequency component; these effects were rescued by choline administration. Interestingly, the protective effects of choline could be partially reversed by administration of the muscarinic receptor antagonist atropine. This suggests that choline might be a promising adjunct therapeutic agent to alleviate DOX-induced cardiotoxicity.

Section: Discussionmentioning

confidence: 99%

Choline Protects the Heart from Doxorubicin-Induced Cardiotoxicity through Vagal Activation and Nrf2/HO-1 Pathway

Guo

Oxidative Medicine and Cellular Longevity

et al. 2022

“…The reduction of total reactive antioxidant capacity in patients with POAG is reduced by 60-70%, which indicates that these patients might be more susceptible to damage from oxidative stress [6,43]. In 2017, Cheng et al found that compared with normal human trabecular meshwork cells, Nrf2 expression was down-regulated in glaucomatous trabecular meshwork cells, e921514-2 and in both cell types, the overexpression of Nrf2 promoted cell viability and reduced cell apoptosis [44]. Also, in 2016, Wang et al showed that microRNA-93 (miRNA-93) inhibited the cell viability and induced apoptosis of the glaucomatous trabecular meshwork cells via the suppression of Nrf2 [45].…”

Section: Oxidative Stress Glaucoma Trabecular Meshwork Cells and Nrf2mentioning

confidence: 99%

The Potential Role of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) in Glaucoma: A Review

Zheng

2020

Med Sci Monit

Departmental sources Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a regulator of many biological processes and plays an essential role in preventing oxidation, inflammation, and fibrosis. In the past 20 years, there has been increasing research on the role of Nrf2 and oxidative stress in human glaucoma, including the roles of inflammation, trabecular meshwork cells, retinal ganglion cells, Tenon's capsule, antioxidants, fibrosis, and noncoding RNAs. Studies have shown that the upregulation of Nrf2 can reduce damage from oxidative stress in the trabecular meshwork cells and the retinal ganglion cells, reduce fibrosis in Tenon's capsule fibroblasts, which may reduce the progression of fibrosis after surgery for glaucoma. The regulatory roles of Nrf2, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and exogenous compounds on trabecular meshwork cells (TMCs) and retinal ganglion cells have also been studied. The use of Nrf2 agonists, including noncoding RNAs, control the expression of Nrf2 through signaling pathways that continue to be investigated to identify effective treatments to improve clinical outcome following surgery for glaucoma. This review of publications between 1999 and 2019 aims to focus on the potential mechanisms of Nrf2 in the occurrence and development of glaucoma and the prognosis following surgical treatment. Also, several factors that induce the expression of Nrf2 in trabecular meshwork cells, retinal ganglion cells, and human Tenon's capsule fibroblasts are discussed.

“…TMCs under OS present typical changes observed in POAG, including extracellular matrix (ECM) accumulation, cell apoptosis, cell death, changes in the structure and function of the cytoplasm as well as lysosomes [102], and cytoskeletal disruption [103]. Cheng et al found that Nrf2 expression was downregulated in glaucomatous TMCs compared to human TMCs and that in both cell types, the overexpression of Nrf2 could promote viability and reduce apoptosis [104].…”

Section: Fuchs' Endothelial Corneal Dystrophy (Fecd)mentioning

confidence: 99%

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

Oxidative Medicine and Cellular Longevity

Zhao

Zhang

et al. 2020

Nuclear factor- (erythroid-derived 2-) like 2 (Nrf2) is a regulator of many processes of life, and it plays an important role in antioxidant, anti-inflammatory, and antifibrotic responses and in cancer. This review is focused on the potential mechanism of Nrf2 in the occurrence and development of ocular diseases. Also, several Nrf2 inducers, including noncoding RNAs and exogenous compounds, which control the expression of Nrf2 through different pathways, are discussed in ocular disease models and ocular cells, protecting them from dysfunctional changes. Therefore, Nrf2 might be a potential target of protecting ocular cells from various stresses and preventing ocular diseases.