Deconvoluting Wavelengths Leading to Fluorescent Light Induced Inflammation and Cellular Stress in Zebrafish (Danio rerio)

Abstract

Fluorescent light (FL) has been shown to induce a cellular immune and inflammatory response that is conserved over 450 MY of evolutionary divergence and among vertebrates having drastically different lifestyles such as Mus musculus, Danio rerio, Oryzias latipes and Xiphophorus maculatus. This surprising finding of an inflammation and immune response to FL not only holds for direct light receiving organs (skin) but is also observed within internal organs (brain and liver). Light responsive genetic circuitry initiated by the IL1B regulator induces a highly conserved acute phase response in each organ assessed for all of biological models surveyed to date; however, the specific light wavelengths triggering this response have yet to be determined so investigation of mechanisms and/or light specific molecule(s) leading to this response are difficult to assess. To understand how specific light wavelengths are received in both external and internal organs, zebrafish were exposed to specific 50 nm light wavebands spanning the visible spectrum from 300-600 nm and the genetic responses to each waveband exposure were assessed. Surprisingly, the induced cellular stress response previously observed following FL exposure is not triggered by the lower "damaging" wavelengths of light (UVB and UVA from 300-400 nm) but instead is maximally induced by higher wavelengths ranging from 450-500 nm in skin to 500-600 nm in both brain and liver). Although both research animals and humans are spending increasing amounts of time indoors and under commonly used fluorescent light bulbs, little is known about potential health and genetic effects due to use of this type of artificial light. Recently, the genetic effects of fluorescent light (FL, "cool" white, 4100 K) exposure were investigated and surprisingly this light source was found to induce a highly conserved inflammatory and cellular immune genetic response in three biomedical fish models and the hairless mouse 1,2. Thus, the conserved FL inflammatory/immune response spans ~450 MY of evolution, is observed in both a direct light receiving organ, skin, as well as in brain and liver. The skin and the brain showed up-regulation of the inflammation/immune response in all animals tested. However, in the liver, even though the same genetic pathways and upstream regulators were modulated in both aquatic and terrestrial vertebrates, the mouse liver exhibited a suppressed response rather than up-regulation as in the fishes. This may be due to the nocturnal lifestyle of the mouse and the liver's ability to adjust its gene expression patterns to metabolic cycles, rather than to light regulation. Regardless, the interesting genetic conservation of response to FL is reported in vertebrates spanning different environmental niches (new world tropical versus old world marsh lands), reproductive mechanism (oviparous versus viviparous), and lifestyle (diurnal versus nocturnal). Thus, we speculate this non-circadian based light response is deeply imbedded within the vertebrate genome. Fluorescent light (...