Hereditary Optic Neuropathies



Optic neuropathies of either hereditary or acquired origin are characterized by similar clinical manifestations due to a common underlying pathophysiology of mitochondrial dysfunction. These optic neuropathies demonstrate preferential involvement of the papillomacular bundle (PMB) fibers, which are most energy dependent and most susceptible to oxidative injury. The hallmark of a mitochondrial optic neuropathy (MON) is characterized by symmetric visual loss, loss of high spatial frequency contrast sensitivity, early and profound loss of color vision, central or cecocentral visual field defects, preferential loss of the PMB, and eventual temporal pallor of the optic disc.

MONs can be grouped into nonsyndromic and syndromic disease based on the presence of associated multisystemic mitochondrial disorders. Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA) are the paradigm of hereditary nonsyndromic MONs. Syndromic optic neuropathies can be further divided into mitochondrial DNA (mtDNA)-based disorders and nuclear DNA-based disorders.

While LHON is caused by point mutations in the mtDNA, DOA is caused by mutations in the nuclear gene OPA1, which encodes for a mitochondrial protein. Nevertheless, both conditions share strikingly similar presentations and outcomes as mitochondrial biogenesis requires coordinated interaction of both nuclear and mitochondrial genomes. Optical coherence tomography has become an important diagnostic tool, allowing us to visualize the natural history and characterize different stages of the disease.

Although there is no proven treatment for these diseases, some studies have demonstrated promising results with pharmaceutical agents such as idebenone and EPI-743. Exciting new advancements in gene therapy have also provided hope that the genetic, biochemical, and physiological relationships of this spectrum of disorders may be delineated, providing a new platform for therapeutic and prophylactic strategies. Genetically determined animal models have been created to help us better evaluate and manage these disorders.


Retinal Nerve Fiber Layer Optic Neuropathy Mitochondrial Permeability Transition Pore Retinal Nerve Fiber Layer Thickness Mitochondrial Permeability Transition Pore 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of OphthalmologyDoheny Eye InstituteLos AngelesUSA
  2. 2.Department of Neurology, Neuro-OphthalmologyUniversity of Nevada School of MedicineRenoUSA

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