Altered retinal structure and function in Spinocerebellar ataxia type 3

Toulis, Vasileios; Casaroli-Marano, Ricardo P.; Camós-Carreras, Anna; Figueras‐Roca, Marc; Sánchez-Dalmau, Bernardo; Muñoz, Esteban; Ashraf, Naila S.; Ferreira, Ana F.; Khan, Naheed W.; Marfany, Gemma; Costa, Maria do Carmo

doi:10.1016/j.nbd.2022.105774

Cited by 4 publications

(2 citation statements)

References 54 publications

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“…An increasing number of reports about the role of the ubiquitin-proteasome system in ciliogenesis, retina development, and homeostasis have been published of late, thus hinting at the importance of proteostasis in these finely-tuned pathways [ 44 , 45 , 46 , 47 ]. As such, mutations in genes encoding DUB enzymes have been identified as causative of IRDs and ciliopathies (with or without retinal involvement) [ 16 , 17 , 18 , 20 ]. However, as happens with other rare diseases, there are still patients without a positive genetic diagnosis and the waiting time to reach diagnosis can exceed half a decade [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

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The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Sánchez-Bellver

Férriz-Gordillo

Carrillo-Pz

et al. 2022

IJMS

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Proteins related to the ubiquitin-proteasome system play an important role during the differentiation and ciliogenesis of photoreceptor cells. Mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of inherited retinal dystrophies (IRDs) and ciliopathies. USP48 is a deubiquitinating enzyme whose role in the retina is still unexplored although previous studies indicate its relevance for neurosensory organs. In this work, we describe that a pool of endogenous USP48 localises to the basal body in retinal cells and provide data that supports the function of USP48 in the photoreceptor cilium. We also demonstrate that USP48 interacts with the IRD-associated proteins ARL3 and UNC119a, and stabilise their protein levels using different mechanisms. Our results suggest that USP48 may act in the regulation/stabilisation of key ciliary proteins for photoreceptor function, in the modulation of intracellular protein transport, and in ciliary trafficking to the photoreceptor outer segment.

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Section: Discussionmentioning

confidence: 99%

“…In fact, post-translational ubiquitin and ubiquitin-like modifications play an important role during photoreceptor differentiation and ciliogenesis. Indeed, mutations in several genes involved in ubiquitination and proteostasis have been identified as causative of IRDs and retinal ciliopathies [ 16 , 17 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Sánchez-Bellver

Férriz-Gordillo

Carrillo-Pz

et al. 2022

IJMS

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Seeking Therapies for Spinocerebellar Ataxia: From Gene Silencing to Systems-Based Approaches

Powers

Paulson

Srinivasan

2023

Contemporary Clinical Neuroscience

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NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment

Sone

Ueno

Akagi

et al. 2023

acta neuropathol commun

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The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87–134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.

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Altered retinal structure and function in Spinocerebellar ataxia type 3

Cited by 4 publications

References 54 publications

The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3

Seeking Therapies for Spinocerebellar Ataxia: From Gene Silencing to Systems-Based Approaches

NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment

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