Treatment strategies for mitochondrial optic neuropathies

Abstract

AbstractThree decades have elapsed since the first reports of human disease being directly caused by defects within the mitochondrial genome, including the identification of the m.11778G > A mitochondrial DNA (mtDNA) mutation in patients with Leber hereditary optic neuropathy (LHON). LHON causes severe bilateral visual loss among young adults with an estimated prevalence of 1 in 30 000 in the general population. Most patients carry point mutations in mtDNA with the three most common pathogenic variants being m.3460G > A (MT‐ND1), m.11778G > A (MT‐ND4) and m.14484 T > G (MT‐ND6). LHON carries a poor visual prognosis and patient management remains largely supportive. However, major advances in our understanding of the mechanisms underpinning retinal ganglion cell loss in this mitochondrial disorder are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. The eye is an ideal target organ for gene therapy given its relative ease of anatomical access, but some key issues need to be explored further, in particular, the most efficient gene delivery systems and the optimal window for therapeutic intervention in LHON.