Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

Votruba, Marcela; Moore, Anthony T.; Bhattacharya, Shom Shanker

doi:10.1136/jmg.35.10.793

Cited by 116 publications

(82 citation statements)

References 65 publications

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“…Retina degeneration limited to RGC is also rarely observed in human and is associated with optic atrophy (36). It might have been unnoticed in the only reported case of TR␤ deletion in human who suffered from very low visual acuity and color blindness (37).…”

Section: Retina Degeneration As An Indirect Consequence Of Opc Persismentioning

confidence: 99%

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Baas

Legrand

Samarut

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Thyroid hormone (3,5,3-triiodo-L-thyronine or T3) exerts a pleiotropic activity during central nervous system development. Hypothyroidism during the fetal and postnatal life results in an irreversible mental retardation syndrome. At the cellular level, T3 is known to act on neuronal and glial lineages and to control cell proliferation, apoptosis, migration, and differentiation. Oligodendrocyte precursor cells (OPC) found at birth in the optic nerves are self-renewing cells that normally differentiate during the first 3 weeks of rodent postnatal life into postmitotic myelinating oligodendrocytes. In vitro, the addition of T3 to OPC is sufficient to trigger their terminal differentiation. The present analysis of T3 receptor knockout mice reveals that the absence of all T3 receptor results in the persistence of OPC proliferation in adult optic nerves, in a default in myelination, and sometimes in the degeneration of the retinal ganglion neurons. Thus, T3 signaling is necessary in vivo to promote the complete differentiation of OPC. T hyroid hormone (3,5,3Ј-triiodo-L-thyronine, T3) acts directly at the transcription level by binding to nuclear receptors (TR␣1 and TR␤1, TR␤2, TR␤3) encoded by both TR␣ and TR␤ genes to control a number of physiological and developmental processes. During the late embryonic postnatal period, T3 action is critical for brain development. However, although both hyperthyroidism and hypothyroidism are known to affect directly or indirectly the proliferation, apoptosis, migration, and differentiation of several neuronal and glial cell types (1, 2), only subtle brain defects have been reported to date in the nervous system of TR knockout mice (3, 4). Moreover, knock-in point mutations recently led to contrasting results that are difficult to interpret (5-7). In the rodent optic nerves, oligodendrocyte precursor cells (OPC) differentiate during the first postnatal weeks to give rise to the oligodendrocytes that synthesize myelin around the axons of the retinal ganglion cells (RGC). The in vitro culture of newborn optic nerve OPC (8-10) has offered a unique opportunity to study the precise influence of T3 on the differentiation of this category of glial cells (reviewed in ref. 10). This in vitro model has been extensively investigated, and a number of studies confirmed the direct effect of T3 on OPC differentiation. However, the fact that retinoic acid or glucocorticoids can substitute to T3 to trigger in vitro OPC differentiation (9, 11) raises the question of the respective importance of these factors in vivo. The respective contribution of TR␣ and TR␤ in OPC hormonal response is also unclear (8,10,12). TR␣ is expressed at all stages of oligodendrocyte differentiation, whereas the status for TR␤ remains controversial. Based on RNA and protein analysis, TR␤ expression has been reported to be restricted to differentiated oligodendrocytes (13-16) or to occur in both OPC and oligodendrocytes (9, 17). To clarify the importance of T3 action in vivo and the respective functions of TR␣ and TR␤ in OPC...

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Section: Retina Degeneration As An Indirect Consequence Of Opc Persismentioning

confidence: 99%

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Baas

Legrand

Samarut

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…This disease is characterized by the insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, abnormalities of color vision and caecocentral visual field scotoma (3)(4)(5). Electrophysiological and histopathological studies have suggested that the underlying defect is retinal ganglion cell (RGC) degeneration leading to atrophy of the optic nerve (3,6), as observed in Leber hereditary optic atrophy (LHON) a maternally transmitted disease caused by mtDNA mutations (7).…”

mentioning

confidence: 99%

Effects of OPA1 mutations on mitochondrial morphology and apoptosis: Relevance to ADOA pathogenesis

Olichon

Landes

Arnauné-Pelloquin

et al. 2006

Journal Cellular Physiology

129

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“…17 When the growth is complete, mitochondria then redistribute throughout the neuron. 18 The critical importance of mitochondria to the survival of retinal ganglion cells is emphasised in diseases such as Lebers optic neuropathy or autosomal dominant optic neuropathy, 19,20 where mitochondrial dysfunction results in retinal ganglion cell death and profound vision loss.…”

Section: Modifications For Metabolic Demandmentioning

confidence: 99%

Circulation and axonal transport in the optic nerve

Morgan

2004

Eye

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Retinal ganglion cells are the output cells of the retina whose axons are under considerable metabolic stress in both health and disease states. They are highly polarised to ensure that mitochondria and enzymes involved in the generation of ATP are strategically concentrated to meet the local energy demands of the cell. In passing from the eye to the brain, axons are protected and supported by glial tissues and the blood supply of the optic nerve head is regulated to maintain the supply of oxygen and nutrients to the axons.In spite of this, the optic nerve head remains the point at which retinal ganglion cell axons are most vulnerable to the effects of increased intraocular pressure or ischaemia. Considerable work has been undertaken in this area to advance our understanding on the pathophysiology of axon damage and to develop new strategies for the prevention of retinal ganglion cell death.

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Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy.

Cited by 116 publications

References 65 publications

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Persistence of oligodendrocyte precursor cells and altered myelination in optic nerve associated to retina degeneration in mice devoid of all thyroid hormone receptors

Effects of OPA1 mutations on mitochondrial morphology and apoptosis: Relevance to ADOA pathogenesis

Circulation and axonal transport in the optic nerve

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