Correspondence (reply): In Reply

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.