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Inherited mitochondrial optic neuropathies.

Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF - J. Med. Genet. (2008)

Bottom Line: Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults.Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation.The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited.

View Article: PubMed Central - PubMed

Affiliation: Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, UK.

ABSTRACT
Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited.

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Related in: MedlinePlus

Secondary factors interacting with the primary mtDNA Leber hereditary optic neuropathy mutation to precipitate visual loss. ATP, adenosine triphosphate; ROS, reactive oxygen species.
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jmg-46-03-0145-f02: Secondary factors interacting with the primary mtDNA Leber hereditary optic neuropathy mutation to precipitate visual loss. ATP, adenosine triphosphate; ROS, reactive oxygen species.

Mentions: An intriguing feature of LHON is that only ∼50% of males and ∼10% of females who harbour one of the three primary mutations actually develop the optic neuropathy. This incomplete penetrance and predilection for males to lose vision imply that additional genetic and/or environmental factors must modulate the phenotypic expression of LHON (fig 2). Alternatively, the gender bias could also result from a combination of subtle anatomical, hormonal and physiological variations between males and females.


Inherited mitochondrial optic neuropathies.

Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF - J. Med. Genet. (2008)

Secondary factors interacting with the primary mtDNA Leber hereditary optic neuropathy mutation to precipitate visual loss. ATP, adenosine triphosphate; ROS, reactive oxygen species.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2643051&req=5

jmg-46-03-0145-f02: Secondary factors interacting with the primary mtDNA Leber hereditary optic neuropathy mutation to precipitate visual loss. ATP, adenosine triphosphate; ROS, reactive oxygen species.
Mentions: An intriguing feature of LHON is that only ∼50% of males and ∼10% of females who harbour one of the three primary mutations actually develop the optic neuropathy. This incomplete penetrance and predilection for males to lose vision imply that additional genetic and/or environmental factors must modulate the phenotypic expression of LHON (fig 2). Alternatively, the gender bias could also result from a combination of subtle anatomical, hormonal and physiological variations between males and females.

Bottom Line: Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults.Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation.The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited.

View Article: PubMed Central - PubMed

Affiliation: Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, UK.

ABSTRACT
Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited.

Show MeSH
Related in: MedlinePlus