Instability in X chromosome inactivation patterns in AMD: a new risk factor?

Years ago, it was thought that a genetic component was the fundamental cause of a number retinopathy diseases including age related macular degeneration (AMD). Since then, information has emerged about novel genes that contribute to various forms of AMD and other retinopathies that have been eluding researchers for years. In the genetic sense, only the APOE 2 and 4 genes have been found to be a risk factor for sporadic AMD. But, a recent Genome wide association study (GWAS) revealed that an alteration of five SNIPs on the X chromosome in a gene named DIAPH2 may be a susceptibility gene for AMD. Furthermore, the gene DIAPH2 showed to have a polygenic pleiotropy for premature ovarian failure (POF) and AMD in a cohort of women. POF is highly associated with X chromosome skewing, an epigenetic alteration of the inactivation process of the X chromosome. These findings suggest a hypothesis that an epigenetic alteration on the inactivation centres of the X chromosome (or skewing) relates not only to aging, but might be a novel property that affects women with AMD more often than men.

Melatonin and abeta, macular degeneration and alzheimers disease: same disease, different outcomes?

Aging is the common denominator and the highest risk factor for macular degeneration and Alzheimers Disease (AD). Important pathological hallmarks common to both diseases are the presence of amyloid ß (Aß) in the senile plaques of the AD brain and in the drusen of age-related macular degeneration (AMD) patients, oxidative stress, and apoptotic cell death. Data suggest that a common pathogenic mechanism might exist between AMD and AD. Brain and eye depend on redox electrons from pyridinic and flavinic nucleotides to produce ATP, and reactive oxygen intermediates (ROI). Disorganization of mitochondrial structure and decline in mitochondrial oxidative phosphorylation (OXPHOS) functioning, as well as hypometabolism and alterations in mitochondrial DNA are aging features. Because ROI damage and mitochondrial dysregulation are prominent in AMD and AD and their relationship to the redox state is unclear we addressed a new hypothesis according to which the interaction of melatonin vs Aß are intertwined to balance of the intra- and extra-mitochondrial energy production. This balance would be impaired by the ageing process and environmental/genetic factors, ultimately leading to AD and /or AMD.