The Optic Nerve at Stake: Update on Environmental Factors Modulating Expression of Leber’s Hereditary Optic Neuropathy

Abstract

Optic neuropathies are characterized by the degeneration of the optic nerves and represent a considerable individual and societal burden. Notably, Leber’s hereditary optic neuropathy (LHON) is a devastating vision disease caused by mitochondrial gene mutations that hinder oxidative phosphorylation and increase oxidative stress, leading to the loss of retinal ganglion neurons and axons. Loss of vision is rapid and severe, predominantly in young adults. Penetrance is incomplete, and the time of onset is unpredictable. Recent findings revealed that the incidence of genetic LHON susceptibility is around 1 in 1000, much higher than believed till now. Environmental factors are critical in LHON triggering or severity. Families at risk have a very strong demand for how to prevent the onset or limit the severity of the disease. Here, we review recent knowledge of the extrinsic determinants of LHON expression, including lifestyle, dietary supplements, common chemicals, and drugs.

Optimised, Broad NGS Panel for Inherited Eye Diseases to Diagnose 1000 Patients in Poland

“…For nine patients with RPE65 mutations (almost 1% of our cohort), there is already a gene therapy available, even if it is not fully efficient. Idebenone treatment seems a promising option for LHON/LHONAR patients not only with mtDNA but also with DNAJC30 variants and the type of mutation has a prognostic significance [ 65 ]. For other patients with positive genetic results, involving pathogenic variants in most frequently mutated genes (such as ABCA4 and RPGR ), there will likely be new therapies available soon, with genome editing as the most plausible option.…”