A topical combination of vitamin C, vitamin E and ferulic acid (CE Ferulic, SkinCeuticals) appears to provide protection against skin damage induced by infrared A (IR-A) radiation, said Jean T. Krutmann, M.D., professor of dermatology and environmental medicine and director at the IUF – Leibniz Research Institute for Environmental Medicine, D?sseldorf, Germany, at the 70th annual meeting of the American Academy of Dermatology.
San Diego - A topical combination of vitamin C, vitamin E and ferulic acid (CE Ferulic, SkinCeuticals) appears to provide protection against skin damage induced by infrared A (IR-A) radiation, said Jean T. Krutmann, M.D., professor of dermatology and environmental medicine and director at the IUF – Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany, at the 70th annual meeting of the American Academy of Dermatology.
About 31 percent of the solar energy reaching the earth's surface falls into the near-infrared or IR-A (765 nm to 1,440 nm) wavelength, Dr. Krutmann says.
IR-A penetrates skin much more deeply than UV radiation does, he says, and it directly affects dermal fibroblasts, by upregulating matrix metalloproteinase-1 (MMP-1) expression, for example, which leads to rarefication of collagen fibers and skin wrinkling.
In the first prospective clinical trial to investigate the effect of IR-A in human skin, two-thirds of subjects exposed to IR-A experienced upregulation of MMP-1, specifically within the dermis, but not the epidermis (Schroeder P, Lademann J, Darvin ME, et al. J Invest Dermatol. 2008;128(10):2491-2497. Epub 2008 May 1). This trial also showed that IR-A radiation significantly decreased the antioxidant content of human skin, and that topically applying appropriate antioxidants prevented IR-A radiation-induced MMP-1 expression.
However, Dr. Krutmann says, the effects of IR-A go beyond MMP-1 expression and potentially include development of skin cancer. A team of investigators including Dr. Krutmann exposed primary dermal fibroblasts taken from three healthy volunteers to IR-A (860 J/cm2) and compared changes to unirradiated control samples. Ultimately, this trial showed that IR-A exposure resulted in upregulation of 250 genes and downregulation of 349 genes (Calles C, Schneider M, Macaluso F, et al. J Invest Dermatol. 2010;130(6):1524-1536. Epub 2010 Feb 4).
Mechanism of action
The mechanism by which IR-A damages skin cells differs from the mechanisms of UVA and UVB radiation, Dr. Krutmann says. In terms of chromophores, "Most of the IR-A radiation is absorbed in the mitochondria; in particular, certain components of the mitochondrial respiratory chain (Karu T. J Photochem Photobiol B. 1999;49(1):1-17). We wondered whether this absorption in the mitochondria was, in fact, functionally relevant for IR-A radiation-induced gene regulation."
To explore this question, Dr. Krutmann and colleagues chemically inhibited the respiratory function of mitochondria by using rotenone, antimycin A and thenoyltrifluoroacetone (TTFA). "In all three cases, when we interfered with the electron transport chain and then irradiated the (samples) with IR-A, interrupting the electron transport chain completely abrogated the capacity of these fibroblasts to upregulate MMP-1 expression (Schroeder P, Pohl C, Calles C, et al. Free Radic Biol Med. 2007;43(1):128-135. Epub 2007 Apr 10)," he says, adding that this effect was highly specific to IR-A (p<0.05) because investigators did not see the same inhibitory effect when they irradiated samples with UVA or UVB.
"We did many other experiments," he says. "For example, we overexpressed a protein to increase the number of mitochondria, and by doing so we could make the cells more sensitive to IR-A radiation. We could also show that the initiating event is an increased production of reactive oxygen species (ROS) within the mitochondria. This can be done by using specific fluorescent probes which can only detect ROS that are being produced within the mitochondria."
Dr. Krutmann and colleagues developed a signaling model for IR-A radiation in which IR-A is absorbed within the mitochondria. Subsequently, "The first measurable event is an increase in intramitochondrial ROS production - in other words, oxidative stress," he says.
The signal then leaves the mitochondria, and the next measurable event is an increase in cytoplasmic calcium concentration, Dr. Krutmann says. "This calcium is not coming from outside. It's coming from intracellular calcium stores." Ultimately, "The response reaches the nucleus, and there is increased mRNA expression of MMP-1. Such a response, which is not being initiated in the nucleus but in ordinals such as the mitochondria, and then goes to the nucleus, is called a retrograde signaling response."
This model led Dr. Krutmann and colleagues to theorize that to protect the skin against IR-A damage, "You just have to find antioxidants which preferentially localize with the mitochondria and can stop the signal cascade at the very beginning," he says.