ABSTRACT
Aging is a leading cause of vision loss globally, directly resulting from numerous metabolic, nutritional, or environmental insults or an indirect development of ocular or systemic diseases. Nrf2 is the key controller of the redox homeostatic gene regulatory network, and the Nrf2-Keap1 complex is known as one of the main cellular defense mechanisms against oxidative stress. Nrf2 is localized to many cell types, including numerous ocular cells, as a crucial regulator of cellular redox homeostasis. Nrf2 has been implicated in protecting against oxidative stress in lens epithelia. The Nrf2/Keap1/ARE signaling pathway has been implicated as a significant cell defense mechanism against oxidative stresses. Nrf2-dependent antioxidant protection by overproduction of ROS and/or DNA damage and subsequent demethylation of Keap1 is suppressed by chronic stress, which leads to Nrf2 loss and age-related eye disease development. Numerous natural compounds containing polyphenols have been shown to target directly or indirectly the Nrf2/Keap1/ARE signaling pathway.
