Date Published: July 19, 2017
Publisher: John Wiley and Sons Inc.
Author(s): Xiu‐Fen Liu, Ji‐Long Hao, Tian Xie, Tayyab Hamid Malik, Cheng‐Bo Lu, Cong Liu, Chang Shu, Cheng‐Wei Lu, Dan‐Dan Zhou.
Cataract is one of the most important causes of blindness worldwide, with age‐related cataract being the most common one. Agents preventing cataract formation are urgently required. Substantial evidences point out aggravated oxidative stress as a vital factor for cataract formation. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/Kelch‐like erythroid‐cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1) system is considered as one of the main cellular defense mechanisms against oxidative stresses. This review discusses the role of Nrf2 pathway in the prevention of cataracts and highlights that Nrf2 suppressors may augment oxidative stress of the lens, and Nrf2 inducers may decrease the oxidative stress and prevent the cataract formation. Thus, Nrf2 may serve as a promising therapeutic target for cataract treatment.
Accumulating evidence indicates that oxidative stress increases the injuries in the lens cell through oxidation of proteins, DNA damage, membrane lipid peroxidation, ER stress, UPR activation, and imbalance in calcium homeostasis, etc., all of which contribute to cataractogensis. The Nrf2/Keap1/ARE signaling system is now regarded as one of the major cell defense mechanisms against oxidative stresses. Hence, the stimulation of the Nrf2‐ARE signaling pathway has been evaluated as a crucial target for the design and synthesis of new agents for cataracts. Recently, natural compounds are a key source of Nrf2 inducers, which have been extensively studied. Agents in this article reviewed have illustrated most remarkable effects in vitro and in vivo models, protecting HLECs against oxidative stress, reducing the aberrant proteins and preventing the formation of cataract (Fig. 2). All those promising effects have been associated with the antioxidant and Nrf2 inducing effects of the compounds studied. In conclusion, the Nrf2/Keap1/ARE signaling pathway is a promising preventive and therapeutic target against oxidative stress for cataracts. Nrf2 inducers should be considered as an excellent target to start clinical trials.
The topic was conceptualized by CWL. XFL, and DDZ, and JLH contributed to the literature database search, and writing of the manuscript. TX, CBL, CL, and CS contributed to vital revising. THM contributes to English Polishing.
It was funded by Development and Reform Commission of Jilin Province [2015Y031‐1] and The First Hospital of Jilin University Grant [JDYY72016055].