Mitochondrial DNA common deletion in the human eye: A relation with corneal aging

The most frequent mitochondrial DNA (mtDNA) mutation is a 4977 bp deletion known as the common deletion (mtDNACD4977). mtDNACD4977 is related to skin photo-aging and to chronological aging of cells with high-energy demands such as neurons and muscle cells. The human eye contains both sun-exposed (cornea, iris) and high-energy demand structures (retina). In this study, we employed a highly sensitive quantitative PCR technique to determine mtDNACD4977 occurrence in different structures of the human eye. We found that the cornea, the most anterior structure of the eye, contains the highest amount of mtDNACD4977 (2.6%, 0.25% and 0.06% for the cornea, iris and retina, respectively). Within the cornea, mtDNACD4977 is almost exclusively found in the stroma, the cellular layer conferring transparency and rigidity to the human cornea (8.59%, 0.13% and 0.05% in the stroma, endothelium and epithelium, respectively). Moreover, we show that mtDNACD4977 accumulates with age in the corneal stroma. Taken together, our results suggest that mtDNACD4977 is related to photo-aging rather than chronological aging in the human eye. Similar to the involvement of mtDNACD4977 in skin photo-aging phenotypes, we believe that the clinical manifestations of corneal aging, including clouding and stiffening, are associated with the accumulation of mtDNACD4977 in the corneal stroma.

► In the human eye, the mtDNA common deletion level is concentrated in the cornea.
► Within the human cornea, mtDNA common deletion is concentrated in the stroma.
► mtDNA common deletion is concentrated in the central region of the cornea
► mtDNA common deletion accumulates during human corneal aging.