This report describes optic atrophy 1 (OPA1), which is a subtype of optic atrophy; OPA1 exhibits autosomal dominant inheritance. The human gene implicated in this disease is also designated OPA1; it encodes encodes a protein that localizes to the inner mitochondrial membrane and regulates several important cellular processes including stability of the mitochondrial network and mitochondrial bioenergetic output. There is a single orthologous gene in Drosophila, Dmel\Opa1. The human OPA1 gene is implicated in multiple other diseases; see MIM:605290. For information on fly models of disease using the fly gene, see 'optic atrophy syndromes, OPA1-related' (FBhh0000642).
Multiple UAS constructs of the human Hsap\OPA1 gene, including wild-type and variants implicated in disease, have been introduced into flies. See the 'Disease-Implicated Variants' table below. Partial heterologous rescue (functional complementation) has been demonstrated. Variants of Hsap\OPA1 implicated in disease fail to rescue or exhibit a lower degree of rescue. More severe mutations are associated with optic atrophy plus syndrome (FBhh0000645) and less severe with this disease, optic atrophy 1. This analysis allows quantitative evaluation of loss-of-function severity by comparing the rescue capabilities of known or newly identified variants, thus allowing rapid determination of the disease subtype.
[updated Oct. 2024 by FlyBase; FBrf0222196]
Optic atrophy refers to the death of the retinal ganglion cell axons that comprise the optic nerve. Optic atrophy is an end stage that arises from myriad causes of optic nerve damage anywhere along the path from the retina to the lateral geniculate. Since the optic nerve transmits retinal information to the brain, optic atrophy is associated with vision loss. Optic atrophy is somewhat of a misnomer as atrophy implies disuse and optic nerve damage is better termed optic neuropathy. [http://eyewiki.aao.org/Optic_Atrophy]
[OPTIC ATROPHY 1; OPA1](https://omim.org/entry/165500)
[OPA1 MITOCHONDRIAL DYNAMIN-LIKE GTPase; OPA1](https://omim.org/entry/605290)
Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998; pubmed:9514489). [from MIM:165500; 2017.10.02]
Optic atrophy-1 (OPA1) is caused by heterozygous mutation in the OPA1 gene. [from MIM:165500; 2017.10.02]
The OPA1 gene encodes a protein that localizes to the inner mitochondrial membrane and regulates several important cellular processes including stability of the mitochondrial network, mitochondrial bioenergetic output, and sequestration of proapoptotic cytochrome c oxidase molecules within the mitochondrial cristae spaces (summary by Yu-Wai-Man et al., 2010; pubmed:20157015). [from MIM:605290; 2017.10.02]
One to one (1 human to 1 Drosophila).
