Functional observations in vitamin A deficiency: diagnosis and time course of recovery

McBain, Vikki A.; Egan, Catherine; Pieris, S.; Supramaniam, G; Webster, Andrew R.; Bird, Alan C.; Holder, Graham E.

doi:10.1038/sj.eye.6702212

Cited by 55 publications

(51 citation statements)

References 19 publications

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“…It is intriguing that cone function persists so well despite low serum vitamin A, whether from Fenretinide or nutritional deprivation [14]. An explanation may lie in the existence of other mechanisms besides retinol binding protein that can support the cellular uptake of vitamin A in the eye, [15][16][17][18] and perhaps provide sufficient retinoid for cone function.…”

Section: Discussionmentioning

confidence: 99%

Total rod ERG suppression with high dose compassionate Fenretinide usage

2008

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Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.

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Section: Discussionmentioning

confidence: 99%

Total rod ERG suppression with high dose compassionate Fenretinide usage

2008

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“…This should be distinguished from the Schubert-Bornschein type of ERG abnormalities in which scotopic a-wave amplitude is normal or minimally subnormal. In cases of Riggs-type CSNB, an electronegative waveform likely represents the dark-adapted cone system contribution to the bright flash ERG, exposed in the absence of rod function, similar to ERGs associated with sub-acute vitamin A deficiency (McBain et al, 2007). A similar ERG characteristic to bright flashes may be seen in healthy subjects under LA conditions (photopic hill phenomenon) (Rufiange et al, 2003;Wali and Leguire, 1992); the b-wave attenuates relative to the a-wave at high flash intensities due to progressive reduction of the ONcomponent and delay in the OFF-component (Ueno et al, 2004).…”

Section: Riggs-type Of Csnb (Riggs 1954) (Csnb With Photoreceptor Dymentioning

confidence: 97%

“…However, in spite of ERG recovery following extended DA, the rod and cone-mediated ERGs had worsened since childhood. It is noted that (McBain et al, 2007;Sergouniotis et al, 2011a). After overnight dark adaptation of the right eye, ERGs showed partial recovery but a second bright flash (DA 3.0; inter-stimulus interval 60s) resulted in marked ERG reduction.…”

Section: Fundus Albipunctatusmentioning

confidence: 99%

Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

Zeitz

Robson

Audo

2015

Progress in Retinal and Eye Research

280

382

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“…Those patients homozygous for the p.Met454Thr allele demonstrated a reduction in the photopic b to a ratio, a feature not typically associated with primary photoreceptor degeneration. Although a reduced b-to a-wave ratio can occur in the bright flash dark-adapted ERG in cone isolated retinas due to vitamin A deficiency, 20 or RDH5 mutation, 21 when rod loss is so severe that all remaining signals arise in dark-adapted cones, the photopic ERGs do not exhibit such a phenomenon. The reduced photopic b to a ratio in the present series thus indicates dysfunction after phototransduction beyond the photoreceptor outer segment.…”

Section: Figurementioning

confidence: 99%

Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

Khan¹,

El‐Asrag

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Khan KN, El-Asrag ME, Ku CA, et al.; for NIHR BioResource-Rare Diseases and UK Inherited Retinal Disease Consortium. Specific alleles of CLN7/ MFSD8, a protein that localizes to photoreceptor synaptic terminals, cause a spectrum of nonsyndromic retinal dystrophy. Invest Ophthalmol Vis Sci. 2017;58:290658: -291458: . DOI:10.1167 PURPOSE. Recessive mutations in CLN7/MFSD8 usually cause variant late-infantile onset neuronal ceroid lipofuscinosis (vLINCL), a poorly understood neurodegenerative condition, though mutations may also cause nonsyndromic maculopathy. A series of 12 patients with nonsyndromic retinopathy due to novel CLN7/MFSD8 mutation combinations were investigated in this study. METHODS.Affected patients and their family members were recruited in ophthalmic clinics at each center where they were examined by retinal imaging and detailed electrophysiology. Whole exome or genome next generation sequencing was performed on genomic DNA from at least one affected family member. Immunofluorescence confocal microscopy of murine retina cross-sections were used to localize the protein. RESULTS.Compound heterozygous alleles were identified in six cases, one of which was always p.Glu336Gln. Such combinations resulted in isolated macular disease. Six further cases were homozygous for the variant p.Met454Thr, identified as a founder mutation of South Asian origin. Those patients had widespread generalized retinal disease, characterized by electroretinography as a rod-cone dystrophy with severe macular involvement. In addition, the photopic single flash electroretinograms demonstrated a reduced b-to a-wave amplitude ratio, suggesting dysfunction occurring after phototransduction. Immunohistology identified MFSD8 in the outer plexiform layer of the retina, a site rich in photoreceptor synapses.CONCLUSIONS. This study highlights a hierarchy of MFSD8 variant severity, predicting three consequences of mutation: (1) nonsyndromic localized maculopathy, (2) nonsyndromic widespread retinopathy, or (3) syndromic neurological disease. The data also shed light on the underlying pathogenesis by implicating the photoreceptor synaptic terminals as the major site of retinal disease.

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Functional observations in vitamin A deficiency: diagnosis and time course of recovery

Abstract: Aims To describe the effects of vitamin A deficiency (VAD) on retinal function and the subsequent recovery following treatment in

Cited by 55 publications

References 19 publications

Total rod ERG suppression with high dose compassionate Fenretinide usage

Total rod ERG suppression with high dose compassionate Fenretinide usage

Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms

Specific Alleles of CLN7/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy

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