Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

Sarzi, Emmanuelle; Seveno, Marie; Angebault, Claire; Miléa, Dan; Rönnbäck, Cecilia; Quilès, Mélanie; Adrian, Mathias; Grenier, Joanna; Caignard, Angélique; Lacroux, Annie; Lavergne, Christian; Reynier, Pascal; Larsen, Michael; Hamel, Christian; Delettre, Cécile; Lenaers, Guy; Müller, Agnès

doi:10.1093/hmg/ddx376

Cited by 10 publications

(18 citation statements)

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“…121 ). Indeed, mutations in optic atrophy protein 1 (OPA1) (which cause optic atrophy) have been shown to dysregulate mitochondrial steroid production in the retina, promoting apoptosis of retinal ganglion cells 122 .…”

Section: Biosynthesis Of Macromoleculesmentioning

confidence: 99%

“…Genetic links between mitochondria and disease are well established: mutations in many genes that encode proteins critical to mitochondrial function give rise to multisystem hereditary diseases known collectively as the mitochondrial cytopathies. Furthermore, impaired mitochondrial fusion resulting from mutations in OPA1 causes optic atrophy 122 , and from mutations in MFN2 can cause Charcot-Marie-Tooth disease type 2A (a familial neuropathy) 120 . Defective haem biosynthesis can lead to porphyria, deleterious to neuronal function 126 .…”

Section: Role In Disease Pathogenesismentioning

confidence: 99%

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Mitochondria at the neuronal presynapse in health and disease

2018

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Synapses enable neurons to communicate with each other and are therefore a prerequisite for normal brain function. Presynaptically, this communication requires energy and generates large fluctuations in calcium concentrations. Mitochondria are optimized for supplying energy and buffering calcium, and they are actively recruited to presynapses. However, not all presynapses contain mitochondria; thus, how might synapses with and without mitochondria differ? Mitochondria are also increasingly recognized to serve additional functions at the presynapse. Here, we discuss the importance of presynaptic mitochondria in maintaining neuronal homeostasis and how dysfunctional presynaptic mitochondria might contribute to the development of disease.

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Section: Biosynthesis Of Macromoleculesmentioning

confidence: 99%

Section: Role In Disease Pathogenesismentioning

confidence: 99%

Mitochondria at the neuronal presynapse in health and disease

2018

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“…33 Three different Opa1 þ/À mouse models have been characterized. [34][35][36] They all present at~50% reduction of Opa1 protein expression and replicate the human clinical condition, that is, a slowly progressive bilateral optic neuropathy associated with the loss of RGCs. One of these mouse models presents a DOA phenotype with mild extraocular features, including subtle neurologic and metabolic abnormalities, 37 late-onset cardiomyopathy, 38 and increased endurance.…”

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confidence: 79%

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1^delTTAG/+ Mice

Barca

Simard

Sarzi

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Moreover, it is more time-consuming and costly, considering the increased number of animals in studies with several time points. In fact, SD-OCT paved the way to incriminate a new retinal cell type in DOA, the Müller cell 9 . This was done despite the fact that neither single-cell resolution nor specific cell identifications are possible with the system.…”

Section: Discussionmentioning

confidence: 99%

“…This manuscript describes the imaging and quantification of retinal layer thickness, using the example of the Opa1 delTTAG mouse line 8,9 , a model of dominant optic atrophy (DOA)…”

Section: Introductionmentioning

confidence: 99%

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells <em>In Vivo</em>

Jagodzinska

Sarzi

Cavalier

et al. 2017

JoVE

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Structural changes in the retina are common manifestations of ophthalmic diseases. Optical coherence tomography (OCT) enables their identification in vivo-rapidly, repetitively, and at a high resolution. This protocol describes OCT imaging in the mouse retina as a powerful tool to study optic neuropathies (OPN). The OCT system is an interferometry-based, non-invasive alternative to common post mortem histological assays. It provides a fast and accurate assessment of retinal thickness, allowing the possibility to track changes, such as retinal thinning or thickening. We present the imaging process and analysis with the example of the Opa1 mouse line. Three types of scans are proposed, with two quantification methods: standard and homemade calipers. The latter is best for use on the peripapillary retina during radial scans; being more precise, is preferable for analyzing thinner structures. All approaches described here are designed for retinal ganglion cells (RGC) but are easily adaptable to other cell populations. In conclusion, OCT is efficient in mouse model phenotyping and has the potential to be used for the reliable evaluation of therapeutic interventions.

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Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

Cited by 10 publications

References 0 publications

Mitochondria at the neuronal presynapse in health and disease

Mitochondria at the neuronal presynapse in health and disease

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1^delTTAG/+ Mice

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells <em>In Vivo</em>

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Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy

Cited by 10 publications

References 0 publications

Mitochondria at the neuronal presynapse in health and disease

Mitochondria at the neuronal presynapse in health and disease

Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1delTTAG/+ Mice

Optical Coherence Tomography: Imaging Mouse Retinal Ganglion Cells <em>In Vivo</em>

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Targeted Metabolomics Reveals Early Dominant Optic Atrophy Signature in Optic Nerves of Opa1^delTTAG/+ Mice