Blinded by the light: Retinal phototoxicity in the context of safety studies

摘要

In a seminal study published in 1966, Werner K. Noell and associates reported that the "retina of laboratory rats is affected irreversibly by intense light applied for less than an hour or for up to 2 days depending on the experimental conditions." (Noell et al. 1966). They found this effect when the retinas of "normal unanesthetized and unrestrained rats were maintained continuously for 24 hours in an environment illuminated by ordinary fluorescent light bulbs." In an insightful introductory comment, the authors indicated that the "interest in this effect rests mainly on the assumption that any unusual vulnerability of the retina to physical or chemical agents may relate to the cellular abnormalities which lead to retinal degeneration on a hereditary basis." This ushered in an era of intense investigation of the interactions between light and photoreceptor degeneration that has helped unravel the mechanisms of this effect, identify potential consequences to human patients, and develop therapies that could be translated to the clinic (e.g., studies on neuroprotection from light damage by ciliary neurotrophic factor and its eventual use in human clinical trials; LaVail et al. 1992; Tao et al. 2002; Sieving et al. 2006). From 1966 to August 2012, over 184 papers have been published on retinal light damage in rats. In mice, where the same finding was first reported in 1971 (Aoyagi 1971), there have been >134 publications (search: light damage/retina/rat and light damage/retina/mouse with manual review of the search results to eliminate references that are not pertinent).