Electrophysiology in pigment epithelial changes

Nilsson, Sven Erik G.

doi:10.1111/j.1755-3768.1985.tb06831.x

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…More importantly, we did not detect any obvious apoptosis of RPE cells in either the heterozygous or the homozygous KI mice, suggesting that the RPE is largely healthy. We also examined the ionic channel activity of RPE plasma membrane in our KI mouse models by measuring the slow ocular potentials of the ERG c ‐wave after a full dark adaptation (Nilsson, ; Steinberg, ). The c ‐wave amplitudes of the 4‐month‐old KI/KI and WT/KI mice are comparable to those of their WT siblings (Supporting Information ), indicative of a grossly physiologically functional RPE in heterozygous and homozygous KI mice.…”

Section: Resultsmentioning

confidence: 99%

Aberrant RNA splicing is the major pathogenic effect in a knock‐in mouse model of the dominantly inherited c.1430A>G humanRPE65mutation

Furhang

Ray

et al. 2019

Human Mutation

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Human RPE65 mutations cause a spectrum of retinal dystrophies that result in blindness. While RPE65 mutations have been almost invariably recessively inherited, a c.1430A>G (p.(D477G)) mutation has been reported to cause autosomal dominant retinitis pigmentosa (adRP). To study the pathogenesis of this human mutation, we have replicated the mutation in a knock‐in (KI) mouse model using CRISPR/Cas9‐mediated genome editing. Significantly, in contrast to human patients, heterozygous KI mice do not exhibit any phenotypes in visual function tests. When raised in regular vivarium conditions, homozygous KI mice display relatively undisturbed visual functions with minimal retinal structural changes. However, KI/KI mouse retinae are more sensitive to light exposure and exhibit signs of degenerative features when subjected to light stress. We find that instead of merely producing a missense mutant protein, the A>G nucleotide substitution greatly affects appropriate splicing of Rpe65 mRNA by generating an ectopic splice site in comparable context to the canonical one, thereby disrupting RPE65 protein expression. Similar splicing defects were also confirmed for the human RPE65 c.1430G mutant in an in vitro Exontrap assay. Our data demonstrate that a splicing defect is associated with c.1430G pathogenesis, and therefore provide insights in the therapeutic strategy for human patients.

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Section: Resultsmentioning

confidence: 99%

Aberrant RNA splicing is the major pathogenic effect in a knock‐in mouse model of the dominantly inherited c.1430A>G humanRPE65mutation

Furhang

Ray

et al. 2019

Human Mutation

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show abstract

“…The ERG will be delt with in more detail in a following paper, also published in the present issue of Acta Ophtalmol. (Nilsson 1985). The SP is generated across the apical surface of the pigment epithelium, where the cells are connected by tight junctions which constitute a substantial barrier against ion movements.…”

mentioning

confidence: 99%

“…The experimental and clinical aspects of the SP will be dealt with in more detail in a following paper, also published in the present issue of Acta Ophtalmol. (Nilsson 1985). It ought to be pointed out that several hereditary degenerative retinal diseases, e.g.…”

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confidence: 99%

The retinal photoreceptors and the pigment epithelium. Structure and function. Transduction

Nilsson¹

1985

Acta Ophthalmologica

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Retinal Pigment Epithelial Dysfunction in Patients With Pigment Dispersion Syndrome

Greenstein

Seiple²,

Liebmann³

et al. 2001

Arch Ophthalmol

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To test the hypothesis that the retinal pigment epithelial/photoreceptor complex is affected in patients with pigment dispersion syndrome and/or in patients with pigmentary glaucoma.Methods: Electro-oculograms were recorded from patients with pigment dispersion syndrome, pigmentary glaucoma, ocular hypertension, and primary openangle glaucoma and from control subjects. Electrooculograms were recorded during 15 minutes of dark adaptation followed by 15 minutes of light adaptation. For each subject, dark-trough amplitudes, dark-trough latencies, light-peak amplitudes, light-peak latencies, and ratios of the light-peak amplitude to the dark-trough amplitude (Arden ratios) were calculated.Results: A 1-way analysis of variance of the Arden ratios indicated significant differences among the groups of subjects. Results of a post hoc Newman-Keuls test revealed that the mean Arden ratios of patients with pigment dispersion syndrome and patients with pigmentary glaucoma were significantly lower than the mean ratios of the controls, the patients with primary open-angle glaucoma, and those with ocular hypertension. Conclusions:The results provide support for the hypothesis that the integrity of the retinal pigment epithelial/ photoreceptor complex is affected in patients with pigment dispersion syndrome and in those with pigmentary glaucoma. Congenital and/or structural abnormalities of the retinal pigment epithelial/photoreceptor complex should be considered when models of the etiology of pigment dispersion syndrome are proposed.

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Electrophysiology in pigment epithelial changes

Cited by 6 publications

References 37 publications

Aberrant RNA splicing is the major pathogenic effect in a knock‐in mouse model of the dominantly inherited c.1430A>G humanRPE65mutation

Aberrant RNA splicing is the major pathogenic effect in a knock‐in mouse model of the dominantly inherited c.1430A>G humanRPE65mutation

The retinal photoreceptors and the pigment epithelium. Structure and function. Transduction

Retinal Pigment Epithelial Dysfunction in Patients With Pigment Dispersion Syndrome

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