A Comparative Optical Coherence Tomography Study of Spinocerebellar Ataxia Types 3 and 10

Tensini, Fernando Spina; Sato, Mário Teruo; Shiokawa, Naoye; Ashizawa, Tetsuo; Teive, Hélio Afonso Ghizoni

doi:10.1007/s12311-017-0856-7

Cited by 16 publications

(20 citation statements)

References 26 publications

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“…These data suggest a role for atxn3 in retinal ciliogenesis and phagocytosis [ 52 ]. This could explain some cases of retinal alterations found in SCA3 patients [ 53 , 54 , 55 ].…”

Section: Resultsmentioning

confidence: 99%

Zebrafish Models of Autosomal Dominant Ataxias

Quelle-Regaldie

Sobrido‐Cameán

Barreiro‐Iglesias

et al. 2021

Cells

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Hereditary dominant ataxias are a heterogeneous group of neurodegenerative conditions causing cerebellar dysfunction and characterized by progressive motor incoordination. Despite many efforts put into the study of these diseases, there are no effective treatments yet. Zebrafish models are widely used to characterize neuronal disorders due to its conserved vertebrate genetics that easily support genetic edition and their optic transparency that allows observing the intact CNS and its connections. In addition, its small size and external fertilization help to develop high throughput assays of candidate drugs. Here, we discuss the contributions of zebrafish models to the study of dominant ataxias defining phenotypes, genetic function, behavior and possible treatments. In addition, we review the zebrafish models created for X-linked repeat expansion diseases X-fragile/fragile-X tremor ataxia. Most of the models reviewed here presented neuronal damage and locomotor deficits. However, there is a generalized lack of zebrafish adult heterozygous models and there are no knock-in zebrafish models available for these diseases. The models created for dominant ataxias helped to elucidate gene function and mechanisms that cause neuronal damage. In the future, the application of new genetic edition techniques would help to develop more accurate zebrafish models of dominant ataxias.

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“…These data suggest a role for atxn3 in retinal ciliogenesis and phagocytosis [ 52 ]. This could explain some cases of retinal alterations found in SCA3 patients [ 53 , 54 , 55 ].…”

Section: Resultsmentioning

confidence: 99%

Zebrafish Models of Autosomal Dominant Ataxias

Quelle-Regaldie

Sobrido‐Cameán

Barreiro‐Iglesias

et al. 2021

Cells

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“…These findings, together with structural changes in inner retinal layers detected using structural OCT imaging, enable new insights into mechanisms of neurodegeneration related to a possible coupling of neuronal damage in the retina and retinal microvascular changes in neurodegenerative ataxias. [4][5][6][7][8][9][10][11][12][13] Our results are particularly intriguing because retinal vascular alterations, so far documented in AD, in which FIG. 3.…”

Section: Discussionmentioning

confidence: 99%

Microvascular Breakdown Due to Retinal Neurodegeneration in Ataxias

Turski

Faber

et al. 2021

Movement Disorders

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A BS TRACT: Background: Neurodegenerative ataxias are devastating disorders of the cerebellum and spinal cord, accompanied by death of retinal ganglion cells, leading to relentlessly progressive decline of motor coordination and permanent disability. Retinal microvascular affection has not yet been determined. Objectives: The aim of this study is to assess whether retinal microvascular alterations occur and, if so, whether they are concurrent with or follow cell death in the retina in neurodegenerative diseases. Methods: This study involves the cross-sectional observational study of 43 patients with ataxia and 43 controls enrolled from August 1, 2018, to September 30, 2020. The extent of ataxia was determined by the Scale for the Assessment and Rating of Ataxia. Changes in retinal vasculature were examined by optical coherence tomography angiography (OCT-A) and retinal cell and fiber density by OCT in ataxias concurrently. Results: When comparing the ataxia cohort with healthy subjects, ataxia patients exhibited reduced vessel density in the radial peripapillary capillary (RPC) network (P = 0.005), capillary density inside the optic nerve head (cdONH) (P < 0.001), nasal superficial vascular plexus (P = 0.03) as well as reduced ganglion cell layer (GCL) volume (P = 0.04), and temporal peripapillary retinal nerve fiber layer thickness (P = 0.04). Mixed effect analysis modeling laterality confirmed these findings. Conclusions: These findings demonstrate a distinct pattern of concurrent changes in vessel density of the retinal superficial vascular complex, encompassing the superficial vascular plexus, RPC network and cdONH, and retinal GCL volume, providing new insights into the ongoing degeneration in ataxias. Our findings may have relevance for design of novel therapeutic approaches for ataxias and possibly other neurodegenerative diseases.

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“…RNFL thickness correlated inversely with ataxia rating scale scores, which implies RNFL thickness could be considered as a biomarker of the disease severity (Alvarez et al, 2013). On the other hand, no significant association between RNFL thickness and disease duration was observed (Jardim et al, 2001;Spina Tensini et al, 2017).…”

Section: Spinocerebellar Ataxia Typementioning

confidence: 99%

“…The protein encoded by the ataxin gene is ubiquitously expressed. It has been postulated in that many SCAs also affect the retina and/or optic nerve, and other regions of the central and peripheral nervous systems, which can be one of the explanations by the fact that they share the identical embryological origin (neuroectoderm) ( Spina Tensini et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

2020

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Spinocerebellar ataxia (SCA) is a part of the cerebellar neurodegenerative disease group that is diverse in genetics and phenotypes. It usually shows autosomal dominant inheritance. SCAs, always together with the cerebellar degeneration, may exhibit clinical deficits in brainstem or eye, especially retina or optic nerve. Interestingly, autosomal dominant SCAs share a common genetic mechanism; the length of the glutamine chain is abnormally expanded due to the increase in the cytosine-adenine-guanine (CAG) repeats of the disease causing gene. Studies have suggested that the mutant ataxin induces alteration of protein conformation and abnormal aggregation resulting in nuclear inclusions, and causes cellular loss of photoreceptors through a toxic effect. As a result, these pathologic changes induce a downregulation of genes involved in the phototransduction, development, and differentiation of photoreceptors such as CRX, one of the photoreceptor transcription factors. However, the exact mechanism of neuronal degeneration by mutant ataxin restricted to only certain type of neuronal cell including cerebellar Purkinje neurons and photoreceptor is still unclear. The most common SCAs are types 1, 2, 3, 6, 7, and 17 which contain about 80% of autosomal dominant SCA cases. Various aspects of eye movement abnormalities are evident depending on the degree of cerebellar and brainstem degeneration in SCAs. In addition, certain types of SCAs such as SCA7 are characterized by both cerebellar ataxia and visual loss mainly due to retinal degeneration. The severity of the retinopathy can vary from occult macular photoreceptor disruption to extensive retinal atrophy and is correlated with the number of CAG repeats. The value of using optical coherence tomography in conjunction with electrodiagnostic and genetic testing is emphasized as the combination of these tests can provide critical information regarding the etiology, morphological evaluation, and functional significances. Therefore, ophthalmologists need to recognize and differentiate SCAs in order to properly diagnose and evaluate the disease. In this review, we have described and discussed SCAs showing ophthalmic abnormalities with particular attention to their ophthalmic features, neurodegenerative mechanisms, genetics, and future perspectives.

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A Comparative Optical Coherence Tomography Study of Spinocerebellar Ataxia Types 3 and 10

Cited by 16 publications

References 26 publications

Zebrafish Models of Autosomal Dominant Ataxias

Zebrafish Models of Autosomal Dominant Ataxias

Microvascular Breakdown Due to Retinal Neurodegeneration in Ataxias

Ophthalmic Manifestations and Genetics of the Polyglutamine Autosomal Dominant Spinocerebellar Ataxias: A Review

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