Childhood macular dystrophies

Moore, Anthony T.

doi:10.1097/icu.0b013e32832f8002

Cited by 4 publications

(4 citation statements)

References 74 publications

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“…Devastating and untreatable vision loss of children and young adults are caused by certain gene mutations affecting the photoreceptors of the fovea and the surrounding region called the macula [46]. In addition, foveas in the elderly are commonly affected with age-related macular degeneration (AMD), a multifactorial disease with a strong genetic component [47].…”

Section: Resultsmentioning

confidence: 99%

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

et al. 2014

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Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations.

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Section: Resultsmentioning

confidence: 99%

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

et al. 2014

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“…The inherited macular dystrophies are a clinically and genetically heterogeneous group of disorders in which there are structural and functional abnormalities of the central retina [1], [2]. These disorders usually occur in isolation, but they may be associated with a variety of systemic abnormalities.…”

Section: Introductionmentioning

confidence: 99%

Benign Yellow Dot Maculopathy

et al. 2017

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Objective To describe a novel macular phenotype that is associated with normal visual function. Design Retrospective observational case series. Participants 36 affected individuals from 23 unrelated families. Methods This was a retrospective study of patients who had a characteristic macular phenotype. Subjects underwent a full ocular examination, electrophysiological studies, spectral domain optical coherence tomography (OCT) and fundus autofluorescence imaging. Genomic analyses were performed using haplotype sharing analysis and whole-exome sequencing. Main Outcome Measures Visual acuity; Retinal features; Electroretinography; Whole-exome sequencing; Haplotype sharing analysis. Results Twenty-six of 36 subjects were female. The median age at presentation was 15 years, range 5-59 years. The majority of subjects were asymptomatic and either presented following a routine eye examination (22/36 subjects), following screening due to a positive family history (13/36 subjects) or from another ophthalmologist (1/36 subjects). Of the three symptomatic subjects, 2 had reduced visual acuity. Reduced vision was attributed to diagnoses of non-organic visual loss and bilateral ametropic amblyopia with strabismus. Visual acuity was 0.18 LogMAR or better in 30/33 subjects. Color vision was normal in all subjects tested, except for the subject with non-organic visual loss. All subjects had bilateral symmetric multiple yellow dots at the macula. In the majority these were evenly distributed throughout the fovea, but in nine subjects they were concentrated in the nasal parafoveal area. The dots were hyperautofluorescent on fundus autofluorescence imaging. OCT imaging was generally normal, but in 6 subjects subtle irregularities at the inner segment ellipsoid band were seen. Electrophysiological studies identified normal macular function in 17/19 subjects and normal full-field retinal function in all subjects. Whole-exome analysis across 3 unrelated families found no pathogenic variants in known macular dystrophy genes. Haplotype sharing analysis in one family excluded linkage with the North Carolina macular dystrophy (MCDR1) locus. Conclusions A new retinal phenotype is described, which is characterised by bilateral multiple early onset yellow dots at the macula. Visual function is normal and the condition is non-progressive. In familial cases, the phenotype appears to be inherited in an autosomal dominant manner, but a causative gene is yet to be ascertained.

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“…Postnatal degeneration of photoreceptors underlies the most common causes of irreversible blindness. Rod-cone photoreceptor dystrophy is a group of congenital retinal degenerative disorders characterized by postnatal onset of progressive photoreceptor cell loss 1 2 , leading to severe visual impairment and deterioration. Molecular genetic studies have revealed the underlying causes in only ∼50% of these patients.…”

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confidence: 99%

Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

Yan

Cheng

Cho

et al. 2016

Sci Rep

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Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2, although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2-mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.

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Childhood macular dystrophies

Cited by 4 publications

References 74 publications

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

Benign Yellow Dot Maculopathy

Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

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