Phototoxicity of low doses of light and influence of the spectral composition on human RPE cells.

Light is known to induce retinal damage affecting photoreceptors and retinal pigment epithelium. For polychromatic light, the blue part of the spectrum is thought to be the only responsible for photochemical damage, leading to the establishment of a phototoxicity threshold for blue light (445 nm). For humans it corresponds to a retinal dose of 22 J/cm2. Recent studies on rodents and non-human primates suggested that this value is overestimated. In this study, we aim at investigating the relevance of the current phototoxicity threshold and at providing new hints on the role of the different components of the white light spectrum on phototoxicity. We use an in vitro model of human induced pluripotent stem cells (hiPSC)-derived retinal pigment epithelial (iRPE) cells and exposed them to white, blue and red lights from LED devices at doses below 22 J/cm2. We show that exposure to white light at a dose of 3.6 J/cm2 induces an alteration of the global cellular structure, DNA damage and an activation of cellular stress pathways. The exposure to blue light triggers DNA damage and the activation of autophagy, while exposure to red light modulates the inflammatory response and inhibits autophagy.

The blue light hazard and its use on the evaluation of photochemical risk for domestic lighting. An in vivo study.

BACKGROUND: Nowadays artificial light highly increases human exposure to light leading to circadian rhythm and sleep perturbations. Moreover, excessive exposure of ocular structures to photons can induce irreversible retinal damage. Meta-analyses showed that sunlight exposure influences the age of onset and the progression of Age-related macular degeneration (AMD), the leading cause of blindness in people over fifty-year old. Currently, the blue-light hazard (BLH) curve is used in the evaluation of the phototoxicity of a light source for domestic lighting regulations. OBJECTIVES: Here, we analyze the phototoxicity threshold in rats and investigate the role played by the light spectrum, assessing the relevance of the use of the BLH-weighting to define phototoxicity. METHODS: We exposed albino rats to increasing doses of blue and white light, or to lights of different colors to evaluate the impact of each component of the white light spectrum on phototoxicity. Cellular mechanisms of cell death and cellular stress induced by light were analyzed. RESULTS: Our results show that the phototoxicity threshold currently accepted for rats is overestimated by a factor of 50 when considering blue light and by a factor of 550 concerning white light. This is the result of the toxicity induced by green light that increases white light toxicity by promoting an inflammatory response. The content of green in white light induces 8 fold more invasion of macrophages in the retina than the content of blue light. Moreover, the use of BLH-weighting does not evaluate the amount of red radiations contained in white light that mitigates damage by inhibiting the nuclear translocation of L-DNase II and reducing by 33% the number of TUNEL-positive cells. DISCUSSION: These findings question the current methods to determine the phototoxicity of a light source and show the necessity to take into account the entire emission spectrum. As current human phototoxicity thresholds were estimated with the same methods used for rats, our results suggest that they might need to be reconsidered.