Mitochondrial DNA Plays an Important Role
In their paper on the pathogenesis of age-related macular degeneration (AMD), the authors (1) do not mention that mitochondrial DNA (mtDNA) plays an important role in the etiology of AMD. AMD is more than a possibly complement-associated disease accompanied by nuclear DNA (nDNA) dysfunction. While the article makes reference to the genetics of gene defects in the nucleus, the mitochondrial abnormalities associated with AMD are not discussed.
In the meantime, there is growing evidence that defects caused by oxidative stress along the respiratory chain in the mitochondria play a greater role by far in the pathogenesis of AMD than previously thought. Especially oxidative stress due to an apparently genetically determined reduced ability to inactivate highly reactive oxygen species (ROS) in the mitochondria seems to lead to significant mtDNA damage, above all in AMD patients (2). In addition, the DNA repair mechanisms in AMD patients appear to be significantly more affected on a mitochondrial level than on a nuclear DNA (nDNA) level (3). These insights may lead to new treatment options with the potential to prevent the deleterious symptoms in the late stages of AMD by improving metabolic processes on a mitochondrial level early in the disease, even prior to the possible activation of complement-associated pathomechanisms in full-blown late-stage AMD.
Taking mitochondrial processes into account is crucial to developing a deeper understanding of AMD in humans. Awareness of the role of mitochondrial dysfunction in the early stages of AMD is a prerequisite for establishing adequate treatments—before the manifestation of the deleterious symptoms of AMD in the patient.
Ophthalmologist, Düsseldorf, Germany
Conflict of interest statement
The author declares that no conflict of interest exists.
|1.||Weber BHF, Charbel Issa P, Pauly D, Herrmann P, Grassmann F, Holz FG:The role of the complement system in age-related macular degeneration. Dtsch Arztebl Int 2014; 111: 133–8. VOLLTEXT|
|2.||Blasiak J, Glowacki S, Kauppinen A, Kaarniranta K: Mitochondrial and nuclear DNA damage and repair in age-related macular degeneration. Int J Mol Sci 2013; 14: 2996–3010. CrossRef MEDLINE PubMed Central|
|3.||Jarrett SG, Lin H, Godley BF, Boulton ME: Mitochondrial DNA damage and its potential role in retinal degeneration. Prog Retin Eye Res 2008; 27: 596–607.|