PATHOGENIC MECHANISMS FOR DEGENERATION OF RETINAL GANGLION CELLS IN MITOCHONDRIAL OPTIC NEUROPATHIS

Mitochondrial optic neuropathies, which include Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), are a group of inherited blinding diseases characterized by the selective degeneration of only a specific subtype of cells in the retina, the retinal ganglion cells. Most patients loose their vision at early ages (before 10 years for DOA and in the adolescence for man in LHON). The genetic basis for these diseases are now known, in both LHON and DOA being involved proteins which function within the mitochondria. These are small organelles residing within the cell, which function as a powerhouse producing energy for cell life, but also producing poisoning compounds, as the reactive oxygen species, which are dangerous and may induce cell death. Thus, mitochondria exert an important regulatory function for programmed cell death (apoptosis). Despite the genetic origin of these diseases has been discovered, and a lot is known about mitochondrial function, we still do not know why only the retinal ganglion cells are damaged and why not all individuals carrying the genetic defect become affected. Overall, there is no cure for these patients at the moment. The research effort of our laboratories has been focused on mitochondrial optic neuropathies for more than ten years. Our current project is aimed to clarify the above-mentioned enigmas using different strategies, which include further genetic studies and cell modeling of the disease. In particular, we have preliminary results indicating that the cells are able to organize a compensatory strategy to counteract the malfunctioning mitochondria such that some individuals never develop the disease. We strongly believe that the detailed comprehension of these mechanisms will greatly help our understanding of these diseases and will provide tools for a therapy.