We would like to thank Mr. Uebermuth for highlighting the importance of mitochondrial dysfunction in the pathogenesis of AMD. To understand this multifactorial disease it is, of course, essential to take its complex etiology into consideration which is characterized by so far poorly understood interactions between multiple genetic and non-genetic factors contributing to the transition from a healthy to a diseased retina. Such factors include, among others, polymorphisms of the mitochondrial DNA occurring as defined haplogroups in the population; their modifying effects on nuclear genetic factors are being discussed at present (1). Interestingly, these new studies are finding that such factors also have effects on the expression of the nuclear genes of the alternative complement cascade, leading to a paradigm change in our understanding of mitochondrial-nuclear interactions and, at the same time, are highlighting the key role of the innate immune system in AMD.
Due to the topic’s complexity, we had to focus our article (2) to one aspect of AMD research, which, however, has already opened the way to first therapeutic interventions being evaluated in clinical studies. However, we are aware that recent scientific findings point towards further promising aspects of AMD pathogenesis (such as oxidative damage, lipofuscin accumulation, chronic inflammation), adding new important target structures for the development of future therapies.
On behalf of the authors:
Prof. Dr. rer. nat. H. F. Bernhard
Weber Institute of Human Genetics
University of Regensburg, Germany
Prof. Dr. med. Frank G. Holz
Department of Ophthalmology
University of Bonn, Germany
Conflict of interest statement
Prof. Weber has received fees for consultancy and presentations, as well as reimbursements for travel costs by Alcon and Novartis.
Prof. Holz has received fees for consultancy and presentations by Acucela, Alcon, Allergan, Genentech, Novartis, Roche, Merz, Heidelberg Engineering, and Bayer. He has received reimbursements for travel costs from Roche, Novartis, Genentech, Acuela, and Pfizer.
|1.||Cristina Kenney M, Chwa M, Atilano SR, et al.: Inherited mitochondrial DNA variants can affect complement, inflammation and apoptosis pathways: insights into mitochondrial-nuclear interactions. Hum Mol Genet 2014; 4: [Epub ahead of print]. MEDLINE|
|2.||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.|