Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17

Yen Ju Chan, George Hsiao, Wang Nok Wan, Tsung Min Yang, Chi Hao Tsai, Jaw Jou Kang, Yu Cheng Lee, Te Chao Fang, Yu Wen Cheng*, Ching Hao Li*

*此作品的通信作者

研究成果: Article同行評審

摘要

Blue light is part of the natural light spectrum that emits high energy. Currently, people are frequently exposed to blue light from 3C devices, resulting in a growing incidence of retinopathy. The retinal vasculature is complex, and retinal vessels not only serve the metabolic needs of the retinal sublayers, but also maintain electrolyte homeostasis by forming the inner blood-retinal barrier (iBRB). The iBRB, which is primarily composed of endothelial cells, has well-developed tight junctions. However, with exposure to blue light, the risks of targeting retinal endothelial cells are currently unknown. We found that endothelial claudin-5 (CLDN5) was rapidly degraded under blue light, coinciding with the activation of a disintegrin and metalloprotease 17 (ADAM17), even at non-cytotoxic lighting. An apparently broken tight junction and a permeable paracellular cleft were observed. Mice exposed to blue light displayed iBRB leakage, conferring attenuation of the electroretinogram b-wave and oscillatory potentials. Both pharmacological and genetic inhibition of ADAM17 remarkably alleviated CLDN5 degradation induced by blue light. Under untreated condition, ADAM17 is sequestered by GNAZ (a circadian-responsive, retina-enriched inhibitory G protein), whereas ADAM17 escapes from GNAZ by blue light illuminance. GNAZ knockdown led to ADAM17 hyperactivation, CLDN5 downregulation, and paracellular permeability in vitro, and retinal damage mimicked blue light exposure in vivo. These data demonstrate that blue light exposure might impair the iBRB by accelerating CLDN5 degradation through the disturbance of the GNAZ-ADAM17 axis.

原文English
文章編號31
期刊Fluids and Barriers of the CNS
20
發行號1
DOIs
出版狀態Published - 12月 2023

指紋

深入研究「Blue light exposure collapses the inner blood-retinal barrier by accelerating endothelial CLDN5 degradation through the disturbance of GNAZ and the activation of ADAM17」主題。共同形成了獨特的指紋。

引用此