Chronic retinal injury induced by white LED light with different correlated color temperatures as determined by microarray analyses of genome-wide expression patterns in mice

Abstract

Widely used white light-emitting diodes (LEDs) currently deliver higher levels of blue light than conventional domestic light sources. The high intensity of the blue component is the main source of concern regarding possible health risks of LED to chronic light toxicity to the retina. Therefore, we analyzed retinal injury and genome-wide changes in gene expression induced by white LED light with different correlated color temperatures (CCTs) in a mouse model. Balb/c mice (10 weeks old) were exposed to LED light with CCTs of 2954, 5624, and 7378 K, at different illuminance levels (250, 500, 1000, and 3000 lx) and for different exposure times (7, 14, and 28 days). Hematoxylin and eosin staining revealed that exposure to 7378 K light at 250 lx for 28 days resulted in a significant reduction of outer nuclear layer (ONL) nuclei, whereas 2954 K light at <3000 lx led to only a mild reduction in the number of ONL nuclei. In addition, 5624 and 7378 K light at 3000 lx resulted in a significant increase in TUNEL-positive apoptotic nuclei, which was not found at an illuminance of 1000 lx. Genome-wide expression analyses showed that, compared to a control group, there were 121 upregulated differentially expressed genes (DEGs) and 458 downregulated DEGs found in the 7378 K group, and 59 upregulated and only 4 downregulated DEGs in the 2954 K group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were involved in 341 GO terms and 16 related pathways for the 7378 K group and in 12 GO terms and 7 related pathways for the 2954 K group. Signal pathways related to ubiquitin potentially played an important role in light-induced retinal degeneration. Furthermore, retinal immunohistochemistry (IHC) indicated downregulation of ubiquitin and autophagy function caused by 7378 K light. Taken together, these results indicate that retinal injury in the mice induced by white LED light occurred in a CCT-dependent manner, and that light with a higher CCT was more likely to reduce ONL nuclei; however, the apoptosis pathway may not be the only mechanism involved. Based on genome-wide expression analyses and retinal IHC, the ubiquitin-mediated proteolysis signal pathway may have participated in the induction retinal degeneration.