This web page was produced as an assignment for Genetics 564, a capstone course at UW-Madison.
What is optic atrophy? |
What are cataracts? |
Optic atrophy is the process of damage occurring to the optic nerve which carries information from the eye to the brain. The symptoms can include blurry vision, abnormal color vision or side vision, and dimness. The graphic above depicts a healthy retina and one with damage to the optic nerve. |
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Cataracts occur in the lens of the eye, which helps to focus light onto the back of the eye. Cataracts are associated with the clouding of the lens causing decreased vision and could result in gradual vision loss.
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What is Autosomal Dominant Optic Atrophy and Cataract?
This genetic condition is characterized by early symptoms of vision loss, typically in both eyes, that start as soon as infancy or develop in the first decade of life [1]. Optic atrophy and cataracts can occur due to the aging process, but the appearance of these conditions in young individuals is abnormal.
Disease Prevalence
The Autosomal Dominant Optic Atrophy Association (ADOA) is committed to fighting pediatric blindness and creating awareness for the disease. Find more information, ways to get involved, events, and more on their website.
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Diagnosis
Patients can be diagnosed in childhood due to vision loss. Typically, there is also family history with optic atrophy or cataracts that aids in diagnosis. Eye tests such as Optical Coherence Topography can be performed to assess eye health. Genetic testing is ultimately needed to identify the causal mutation in OPA3. Only ~1% of patients with optic atrophy will have the OPA3 mutation [4].
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Prognosis
Vision loss progresses through puberty and adulthood of individuals, although severity can greatly vary even within the same family. Members of the same family effected by optic atrophy and cataract could range from nearly normal vision to blindness. The majority of patients develop cataracts [5]. Patients can experience less common symptoms such as balance and coordination problems [5].
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Treatment
There are no treatments for optic atrophy. However, therapies for optic atrophy are currently in development. Patients may benefit from low vision aids and genetic counseling. Avoiding certain tobacco, alcohol and certain medications may be advised by a health professional [4].
What is OPA3?OPA3 is a protein-coding gene found on chromosome 19 (19q13.32) and is linked to a form of optic atrophy and cataracts [2]. Mutations in OPA3 causing optic atrophy and cataracts can be inherited via dominant transmission. A person with the OPA3 mutation has a 50% percent chance of passing the condition down to each of their children. |
Figure 1. Chromosome 19 with the location of the OPA3 gene shown by the red line.
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The common mutations associated with autosomal dominant optic atrophy and cataract include, NCBI Reference Sequence: NM_025136.3]: c.277G > A, p.(Gly93Ser); c.313C > G, p.(Gln105Glu) (recurrent mutation); c.10_11insCGCCCG, p.(Val3_Gly4insAlaPro) [6], [7]. However, more mutations are being discovered and this does not encompass every mutation associated with OPA3.
What does OPA3 do?
OPA3 encodes a protein that becomes part of the mitochondria's membrane [3]. The mitochondria are important organelles of the cell that produce energy and are found in animals, plants, and fungi. In humans, nearly every cell in the body contains mitochondria.
The OPA3 protein is associated with mitochondrial fission, where a mitochondrion undergoes division. Knockdowns of the protein have been shown to cause highly elongated mitochondria, while some OPA3 mutations induce mitochondrial fragmentation and increased sensitivity to apoptosis [3]. |
The Mitochondria
"The powerhouse of the cell" |
The gap in knowledge surrounding OPA3
Extensive research is still needed to understand the role of OPA3 in mitochondria, lipid metabolism and cell apoptosis. More studies must be completed to understand the protein domains of OPA3, its interactions with other proteins, and how specific mutations can cause altered function that can lead to optic atrophy and cataracts. |
World Map of Website Users
Created in January of 2024
Image References
1)https://www.researchgate.net/publication/332144652_Assessment_Genetics_Mutations_in_Genes_AMELX_ENAM_MMP20_and_FAM83H_in_Inducate_Amelogenesis_Imperfecta_Syndrome
2) Scientific Image and Illustration Software | BioRender
Figure 1. OPA3 Gene - GeneCards | OPA3 Protein | OPA3 Antibody
2) Scientific Image and Illustration Software | BioRender
Figure 1. OPA3 Gene - GeneCards | OPA3 Protein | OPA3 Antibody