Genotype–phenotype correlations in mitochondrial optic neuropathies

Abstract

Metabolic optic neuropathies present in a very similar fashion but yet show some distinct variations. Investigations have revealed that the common pathologic basis of these optic neuropathies is a dysfunction of oxidative phosphorylation in mitochondria leading to retinal ganglion cell degeneration. This impairment can be genetic or acquired. Leber’s hereditary optic neuropathy and dominant optic atrophy are the two primary inherited optic neuropathies, whereas acquired metabolic optic neuropathies can be due to toxins or nutritional deficiencies. Mitochondria are remarkable cytoplasmic organelles carrying their own DNA and are also influenced by nuclear DNA. The genetic background is pivotal in understanding the molecular mechanisms and the wide spectrum of clinical phenotypes of these disorders. Understanding the genetic, environmental and epigenetic interplays will be important for the development of therapeutic strategies aimed to protect against retinal ganglion cell death.

Keywords::

• autosomal dominant optic atrophy
• Cuban epidemic of optic neuropathy
• Leber’s hereditary optic neuropathy
• mitochondria
• nutritional optic neuropathy
• optic nerve
• oxidative phosphorylation
• retinal ganglion cell
• tobacco–alcohol amblyopia
• toxic optic neuropathy

Financial & competing interests disclosure

Research on optic neuropathies was supported by Telethon-Italy, grant #GGP06233 (VC), IFOND (AS and VC), and Struggling with Leber’s F. (AS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.