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New insights in the genetic and pathophysiology of dominant optic atrophy
Author(s) -
Lenaers Guy
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8015
Subject(s) - biology , mitochondrial dna , optic neuropathy , gene , atrophy , mitochondrion , mitochondrial disease , retinal ganglion cell , genetics , pathophysiology , neuroscience , bioinformatics , optic nerve , endocrinology
Inherited Optic Neuropathies are blinding diseases related to mitochondrial dysfunctions in retinal ganglion cell (RGC). There are two main forms: the Leber Hereditary Optic Neuropathy (LHON) related to mutations in the mitochondrial genome, and the Kjer dominant optic atrophy (DOA) related to mutations in nuclear genes. Since the initial discovery of the OPA1 gene as the major gene causing DOA, the use of NGS disclosed many novel genes responsible for DOA. Beyond the genes recently identified involved in mitochondrial dynamics, we identified novel genes involved in other mitochondrial functions that are crucial for RGC physiology. We report here the pathophysiological analyses of their involvement in mitochondrial physiology and metabolism. These data are shedding novel lights on DOA pathophysiology, beyond mitochondrial dynamics, as novel culprit mechanisms responsible for RGC degeneration, which will condition the design of future therapeutic approaches.