Metabolomic and Biomarker Profiling in Mitochondrial Optic Neuropathies (video)

Mitochondrial optic neuropathies constitute an important cause of registrable blindness in both the paediatric and adult population. The two classical paradigms are Leber hereditary optic neuropathy (LHON), which is a primary mitochondrial DNA (mtDNA) disorder, and autosomal dominant optic atrophy (DOA) secondary to pathogenic mutations within the nuclear gene OPA1 (3q28-q29) that encodes for a mitochondrial inner membrane protein. Recessive and dominant WFS1 mutations have also emerged as an important cause of both isolated and syndromic optic atrophy. WFS1 (4p16.1) encodes for the transmembrane endoplasmic reticulum (ER) protein Wolframin that plays a critical role in calcium homeostasis and interorganellar cross-talk at areas of ER mitochondria; contacts. The defining neuropathological feature of all these mitochondrial optic neuropathies is the preferential loss of retinal ganglion cells (RGCs), but the marked phenotypic variability observed in this patient group and the disease mechanisms that ultimately contribute to RGC loss still need to be clarified further.