Ching-Hao Li , Tsung-Min Yang , Ida Fitriana , Te-Chao Fang , Liang-Huan Wu , George Hsiao , Yu-Wen Cheng
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引用次数: 0
Abstract
Exposure to artificial blue light, one of the most energetic forms of visible light, can increase oxidative stress in retinal cells, potentially enhancing the risk of macular degeneration. Retinal pigment epithelial (RPE) cells play a crucial role in this process; the loss of RPE cells is the primary pathway through which retinal degeneration occurs. In RPE cells, Kelch-like ECH-associated protein 1 (KEAP1) is located in both the nucleus and cytosol, where it binds to nuclear factor erythroid 2-related factor 2 (NRF2) and p62 (sequestosome-1), respectively. Blue light exposure activates the NRF2-heme oxygenase 1 (HMOX1) axis through both canonical and noncanonical p62 pathways thereby reducing oxidative damage, and initiates autophagy, which helps remove damaged proteins. These protective responses may support the survival of RPE cells. However, extended exposure to blue light drastically decreases the viability of RPE cells. This exposure diminishes the ability of KEAP1 to bind to p62 and reduces the level of KEAP1. Inhibition of autophagy does not prevent KEAP1 degradation, the NRF2-HMOX1 axis, or blue-light-induced cytotoxicity. However, proteasome inhibitor along with a transient increase in the amount of KEAP1 in RPE cells, partially restores the p62-KEAP1 complex and reduces blue-light-induced cytotoxicity. In vivo studies confirmed the downregulation of KEAP1 in damaged RPE cells. Mice subjected to periodic blue light exposure exhibited significant atrophy in the outer retina, particularly in the peripheral areas. Additionally, there was a significant decrease in c-wave electroretinography and pupillary light reflex, indicating functional impairments in both visual and nonvisual physiological processes. These data underscore the essential role of KEAP1 in managing oxidative defense and autophagy pathways triggered by blue light exposure in RPE cells.
期刊介绍:
The Journal of Photochemistry and Photobiology B: Biology provides a forum for the publication of papers relating to the various aspects of photobiology, as well as a means for communication in this multidisciplinary field.
The scope includes:
- Bioluminescence
- Chronobiology
- DNA repair
- Environmental photobiology
- Nanotechnology in photobiology
- Photocarcinogenesis
- Photochemistry of biomolecules
- Photodynamic therapy
- Photomedicine
- Photomorphogenesis
- Photomovement
- Photoreception
- Photosensitization
- Photosynthesis
- Phototechnology
- Spectroscopy of biological systems
- UV and visible radiation effects and vision.