The T414G mitochondrial DNA mutation: a biomarker of aging in human eye
Abstract The mitochondrial mutation T414G (mtDNA T414G) has been shown to accumulate in aged and sun-exposed skin. The human eye is also exposed to solar harmful rays. More precisely, the anterior structures of the eye (cornea, iris) filter UV rays and the posterior portion of the eye (retina) is exposed to visible light. These rays can catalyze mutations in mitochondrial DNA such as the mtDNA T414G, but the latter has never been investigated in the human ocular structures. In this study, we have developed a technique to precisely assess the occurrence of mtDNA T414G. Using this technique, we have quantified mtDNA T414G in different human ocular structures. We found an age-dependent accumulation of mtDNA T414G in the corneal stroma, the cellular layer conferring transparency and rigidity to the human cornea, and in the iris. Since cornea and iris are 2 anterior ocular structures exposed to solar UV rays, this suggests that the mtDNA T414G mutation is resulting from cumulative solar exposure and this could make the mtDNA T414G a good marker of solar exposure. We have previously shown that the mtDNA CD4977 and mtDNA 3895 deletions accumulate over time in photo-exposed ocular structures. With the addition of mtDNA T414G mutation, it becomes feasible to combine the levels of these different mtDNA mutations to obtain an accurate assessment of the solar exposure that an individual has accumulated during his/her lifetime.