The therapeutic potential of a calorie-restricted ketogenic diet for the management of Leber hereditary optic neuropathy.

Leber hereditary optic neuropathy (LHON) is a maternally inherited, bilateral, sequential optic neuropathy that usually affects young males. LHON arises from a defect in complex I of the oxidative phosphorylation chain that generates increased reactive oxygen species and causes a decline in cellular ATP production. There exists no cure at present for LHON. Asymptomatic LHON mutation carriers show signs of increased mitochondrial biogenesis that may compensate for the compromise in complex I activity. Partial recovery in LHON is associated with a wider optic disc diameter and a younger age at disease onset, which may allow for greater mitochondrial bioenergetic capacity. Rescuing a mitochondrial bioenergetic deficit soon after disease onset may improve the chances of recovery and reduce visual loss in the second eye. We here propose that a calorie-restricted ketogenic diet has the potential to enhance mitochondrial bioenergetic capacity and should be explored as a potential therapeutic option for treating LHON.

A review of mitochondrial optic neuropathies: from inherited to acquired forms / Revisión de las neuropatías ópticas mitocondriales: de las formas hereditarias a las adquiridas

In recent years, the term mitochondrial optic neuropathy (MON) has increasingly been used within the literature to describe a group of optic neuropathies that exhibit mitochondrial dysfunction in retinal ganglion cells (RGCs). Interestingly, MONs include genetic aetiologies, such as Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), as well as acquired aetiologies resulting from drugs, nutritional deficiencies, and mixed aetiologies. Regardless of an inherited or acquired cause, patients exhibit the same clinical manifestations with selective loss of the RGCs due to mitochondrial dysfunction. Various novel therapies are being explored to reverse or limit damage to the RGCs. Here we review the pathophysiology, clinical manifestations, differential diagnosis, current treatment, and promising therapeutic targets of MON (AU)

En los últimos años, se ha incrementado el uso en la literatura del término neuropatía óptica mitocondrial (MON), para describir un grupo de neuropatías ópticas que presentan una disfunción mitocondrial en las células ganglionares de la retina (RGC). De manera interesante, las MON incluyen etiologías genéticas, tales como Neuropatía Óptica Hereditaria de Leber (LHON) y Atrofia Óptica Dominante (DOA), así como etiologías adquiridas derivadas del consumo de drogas, deficiencias nutricionales y etiologías mixtas. Independientemente de que la causa sea hereditaria o adquirida, los pacientes presentan las mismas manifestaciones clínicas, con pérdida selectiva de RGCs debido a la disfunción mitocondrial. Se están explorando diversas terapias novedosas para revertir o limitar el daño a las RGC. En este documento revisamos la patofisiología, las manifestaciones clínicas, los diagnósticos diferenciales, el tratamiento actual y los prometedores objetivos terapéuticos de las MON (AU)