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

Abstract

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.

Cashew (Anacardium occidentale L.) Nuts Modulate the Nrf2 and NLRP3 Pathways in Pancreas and Lung after Induction of Acute Pancreatitis by Cerulein

“…Nrf2 is a master regulator of protective antioxidant and anti-inflammatory responses. It coordinates the expression of several genes, including not only genes encoding antioxidant enzymes but also a series of genes involved in various processes including respiratory, cardiovascular, cerebrovascular, neurodegenerative and ocular diseases, as well as in tumorigenesis [ 15 , 16 , 17 ]. Under physiological conditions, Nrf2 is sequestered in the cytoplasm by its inhibitor Kelch-like ECH-associated protein 1 (Keap1), which mediates the proteasomal degradation of Nrf2 [ 18 ].…”

1‐O‐Hexyl‐2,3,5‐Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis

“…Nrf2 is a transcription factor and protects cells against oxidative stress, electrophiles, and carcinogenic substances [ 43 , 44 ]. Under regular conditions, Nrf2 is bound to Kelch-like ECH-associated protein 1 (Keap1) in the cytosol and forms an E3 ubiquitin ligase complex, which leads to ubiquitination and proteasomal degradation of Nrf2 [ 45 , 46 ]. However, when cells are exposed to oxidative and electrophilic challenges, Nrf2 is activated, released from Keap1, and binds to the ARE sequences then recruits the transcription of antioxidant defence genes [ 47 – 49 ].…”

Lactobacillus sakei Pro-Bio65 Reduces TNF-α Expression and Upregulates GSH Content and Antioxidant Enzymatic Activities in Human Conjunctival Cells

“…15,16 Such observations may be significant in considering the critical role of oxidative stress in inflammatory processes and, consequently, in the pathogenesis of ocular disorders, such as dry eye disease, cataracts, and pterygium, macular degeneration, keratoconus, diabetic retinopathy, and glaucoma. 17,18 Although several health benefits are associated with probiotics, many concerns arose about shelf-life and safety problems. 19 To reduce the possibility of risk of bacterial translocation and infection, the use of paraprobiotics, nonviable bacteria cells or bacterial components, is a valuable alternative.…”

“… 15 , 16 Such observations may be significant in considering the critical role of oxidative stress in inflammatory processes and, consequently, in the pathogenesis of ocular disorders, such as dry eye disease, cataracts, and pterygium, macular degeneration, keratoconus, diabetic retinopathy, and glaucoma. 17 , 18 …”