Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

Zmysłowska, Agnieszka; Fendler, Wojciech; Waszczykowska, Arleta; Niwald, Anna; Borowiec, Maciej; Jurowski, Piotr; Młynarski, Wojciech

doi:10.1007/s00592-017-1042-6

Cited by 20 publications

(17 citation statements)

References 23 publications

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“…In order to confirm our observations and the fact that corneal changes in this case might depend on the gene and not the species, we carried out experimental tests on a mouse model [ 7 ]. Similarly, in our previous studies, we have documented that progressive retinal thinning is present among patients with Wolfram syndrome [ 2 ]. Thus, the number of mice we evaluated in the current study was low because the design of our project has only a confirmatory not an exploratory approach.…”

Section: Methodssupporting

confidence: 75%

“…We have previously described that the average retinal thickness in WFS patients decreases with the progression of the disease [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…They only differed in the exact target region and background of the strain. Ishihara et al traced the exon 2 gene, Kõks et al exon 8 [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Multiple Retinal Anomalies in Wfs1-Deficient Mice

et al. 2020

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Background: Wolfram syndrome (WFS, OMIM: #222300) is an ultrarare autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy and deafness. It has been reported that the average retinal thickness in WFS patients decreases with the progression of the disease. Aim: To investigate retinal thickness and wolframin expression disorders in Wolfram syndrome 1 gene knockout (Wfs1KO) mice compared to their wild-type (WT) littermates. Materials and methods: Both bulbs with optic nerves of three mice Wfs1WT and three Wfs1KO were taken for the histopathological examination. A strain of knockout mice with mutation in exon 8 was used. Results: No expression of wolframin protein in the retina and neurodegeneration of the optic nerve of Wfs1KO mice as compared among Wfs1WT mice was observed. The mean central retinal thickness was thinner and the retinal thickness/longitudinal diameter ratio was significantly lower in hte Wfs1KO as compared to the Wfs1WT mice. In four (67%) eyeballs of Wfs1KO mice, intra-retinal neovessels were observed. Conclusions: Wfs1KO mice retina with mutation in exon 8 present similar clinical features as patients with WFS in the form of reduced retinal thickness and neurodegeneration of the optic nerve. The presence of proliferative retinopathy observed in Wfs1KO mice requires further investigation.

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Section: Methodssupporting

confidence: 75%

“…We have previously described that the average retinal thickness in WFS patients decreases with the progression of the disease [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

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Multiple Retinal Anomalies in Wfs1-Deficient Mice

et al. 2020

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“…Zmysloska et al reported recently also decline of RNFL in patients with WFS followed on average 22 months. 29 …”

Section: Discussionmentioning

confidence: 99%

Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression

et al. 2018

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Background/aimsTo report alterations in visual acuity and visual pathway structure over an interval of 1–3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination.MethodsAnnual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA).ResultsMean age of the 23 patients with WFS in the study was 13.8 years (range 5–25 years). Mean log minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was subnormal in even the youngest patients with WFS. Average RNFL thickness in patients with WFS was 57±8 µ or ~40% thinner than that measured in normal (94±10 µ) children and adolescents (P<0.01). Lower OR FA correlated with worse visual acuity (P=0.006). Subsequent examinations showed declines (P<0.05) in visual acuity, RNFL thickness and OR FA at follow-up intervals of 12–36 months. However, a wide range of disease severity was evident across ages: some of the youngest patients at their first examination had deficits more severe than the oldest patients.ConclusionThe genetic mutation of WFS causes damage to both pregeniculate and postgeniculate regions of the visual pathway. The damage is progressive. The decline in visual pathway structure is accompanied by declines of visual function. Disease severity differs widely in individual patients and cannot be predicted from their age.

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“…Expression of miRNAs in patients with WFS and their changes over time were analyzed in relation to the results of simultaneous optical coherence tomography (OCT) and MRI tests of central nervous system, which are routinely performed in these patients in order to assess the progression of the disease, as described in detail previously. 12 21 …”

Section: Methodsmentioning

confidence: 99%

Serum microRNA as indicators of Wolfram syndrome’s progression in neuroimaging studies

Zmysłowska

Stańczak

Nowicka

et al. 2020

BMJ Open Diab Res Care

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IntroductionPatients with the ultra-rare Wolfram syndrome (WFS) develop insulin-dependent diabetes and progressive neurodegeneration. The aim of the study was to quantify microRNAs (miRNAs) in sera from patients with WFS, correlate their expression with neurological imaging over time and compare miRNA levels with those observed in patients with type 1 diabetes mellitus (T1DM).Research design and methodsWe quantified miRNA expression (Qiagen, Germany) in two groups of patients: with WFS at study entry (n=14) and after 2 years of follow-up and in 15 glycated hemoglobin-matched (p=0.72) patients with T1DM.ResultsWe observed dynamic changes in the expression of multiple miRNAs in patients with WFS parallel to disease progression and in comparison to the T1DM patients group. Among miRNAs that differed between baseline and follow-up WFS samples, the level of 5 increased over time (miR-375, miR-30d-5p, miR-30e-30, miR-145-5p and miR-193a-5p) and was inversely correlated with macular average thickness, while the expression of 2 (let-7g-5p and miR-22-3p) decreased and was directly correlated with neuroimaging indicators of neurodegeneration.ConclusionsOur findings show for the first time that serum miRNAs can be used as easily accessible indicators of disease progression in patients with WFS, potentially facilitating clinical trials on mitigating neurodegeneration.

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Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

Cited by 20 publications

References 23 publications

Multiple Retinal Anomalies in Wfs1-Deficient Mice

Multiple Retinal Anomalies in Wfs1-Deficient Mice

Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression

Serum microRNA as indicators of Wolfram syndrome’s progression in neuroimaging studies

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