Nutrigenetic reprogramming of oxidative stress.

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Retinal disorders cause irreversible vision loss due to unclear mechanisms, but oxidative stress is a common pathological contributor.
• Nuclear factor erythroid-2-related factor (Nrf2) and its regulator Kelch-like ECH-associated protein 1 (Keap1) are key players in cellular defense against oxidative stress.
• The Nrf2-Keap1 pathway is a promising therapeutic target for mitigating oxidative damage in the retina.

Purpose of the Study:

• To review the protective role of the Nrf2-Keap1 pathway in various retinal tissues.
• To elucidate the complex mechanisms by which Nrf2 protects against retinal degeneration.
• To highlight the potential of targeting the Nrf2-Keap1 pathway for treating inherited and environmental retinal disorders.

Main Methods:

• Literature review focusing on studies investigating the Nrf2-Keap1 pathway in retinal cells.
• Analysis of Nrf2's function in photoreceptors, retinal pigment epithelium, endothelial cells, and retinal ganglion cells.
• Correlation of Nrf2-mediated protection with preservation of functional vision.

Main Results:

• Nrf2 activation preserves photoreceptor survival and function by maintaining oxidation homeostasis.
• In the retinal pigment epithelium, Nrf2 stabilizes oxidation and supports mitochondrial motility and autophagy-related lipid metabolism.
• Nrf2 promotes vascularization in endothelial cells by activating antioxidative and angiogenic factors while inhibiting inflammation, and protects retinal ganglion cells from apoptosis.

Conclusions:

• The Nrf2-Keap1 pathway is a critical endogenous defense mechanism against oxidative stress in the retina.
• Targeting the Nrf2-Keap1 pathway demonstrates significant potential for preserving vision and treating diverse retinal degenerations.
• Understanding this pathway offers a promising avenue for developing universal therapies for vision loss.