Congenital Stationary Night Blindness: Mutation Update and Clinical Variability

Lodha, Nidhi; Loucks, Catrina M.; Beaulieu, Chandree L.; Bech-Hansen, N. Torben

doi:10.1007/978-1-4614-0631-0_48

Cited by 24 publications

(18 citation statements)

References 24 publications

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“…6B). Since rod PRs mediate vision in low-light conditions, our findings may help explain the night-blindness phenotype in some patients with loss-of function mutations in CACNA1F 1 and Cabp4 5 , 22 . On the other hand, we found that cone-mediated (light-adapted) b-wave responses are absent in Ca v 1.4 I756T mice (Fig.…”

Section: Discussionmentioning

confidence: 52%

“…Of multiple classes of Ca v 1 channels (Ca v 1.1–1.4), Ca v 1.4 is thought to be the major Ca v channel at PR synapses. More than 50 mutations in the CACNA1F gene encoding the pore-forming α 1 subunit of Ca v 1.4 are linked to multiple visual disorders including incomplete congenital stationary night blindness type 2 (CSNB2) 1 . The visual phenotypes associated with CSNB2 are heterogeneous and may include abnormal visual acuity, night blindness, myopia, and/or nystagmus 2 …”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

et al. 2013

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Mutations in the gene encoding Cav1.4, CACNA1F, are associated with visual disorders including X-linked incomplete congenital stationary night blindness type 2 (CSNB2). In mice lacking Cav1.4 channels, there are defects in the development of “ribbon” synapses formed between photoreceptors (PRs) and second-order neurons. However, many CSNB2 mutations disrupt the function rather than expression of Cav1.4 channels. Whether defects in PR synapse development due to altered Cav1.4 function are common features contributing to the pathogenesis of CSNB2 is unknown. To resolve this issue, we profiled changes in the subcellular distribution of Cav1.4 channels and synapse morphology during development in wild-type (WT) mice and mouse models of CSNB2. Using Cav1.4-selective antibodies, we found that Cav1.4 channels associate with ribbon precursors early in development and are concentrated at both rod and cone PR synapses in the mature retina. In mouse models of CSNB2 in which the voltage-dependence of Cav1.4 activation is either enhanced (Cav1.4I756T) or inhibited (CaBP4 KO), the initial stages of PR synaptic ribbon formation are largely unaffected. However, after postnatal day 13, many PR ribbons retain the immature morphology. This synaptic abnormality corresponds in severity to the defect in synaptic transmission in the adult mutant mice, suggesting that lack of sufficient mature synapses contributes to vision impairment in Cav1.4I756T and CaBP4 KO mice. Our results demonstrate the importance of proper Cav1.4 function for efficient PR synapse maturation, and that dysregulation of Cav1.4 channels in CSNB2 may have synaptopathic consequences.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

et al. 2013

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“…Indeed, most patients with cCSNB show high co-morbidity with myopia (Lodha et al 2012, Miyake et al 1986). Mutations in both mGluR6 (Wang et al 2016, Xu et al 2009) and NYX (Yip et al 2013, Zhang et al 2007, Zhou et al 2015) have also been associated with myopia.…”

Section: Deficits In On-bc Signaling At the Nexus Of Human Visual Dismentioning

confidence: 99%

The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease

Martemyanov

Sampath

2017

Annu. Rev. Vis. Sci.

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Our robust visual experience is based on the reliable transfer of information from our photoreceptor cells, the rods and cones, to higher brain centers. At the very first synapse of the visual system information is split into two separate pathways, ON and OFF, which encode increments and decrements in light intensity, respectively. The importance of this segregation is borne out in the fact that receptive fields in higher visual centers maintain a separation between ON and OFF regions. In the past decade the molecular mechanisms underlying the generation of ON signals have been identified, which is unique in its use of a G protein signaling cascade. In this review we consider advances in our understanding of G protein signaling in ON bipolar cell dendrites, and how insights about signaling have emerged from visual deficits, mostly night blindness. Studies of G protein signaling in ON-BCs reveal an intricate mechanism that permits the regulation of visual sensitivity over a wide dynamic range.

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“…7 Autosomal-recessive CSNB is estimated to be responsible for approximately 7% of all cases of CSNB, making its prevalence less than 1 in 100,000. 5 Clinical exam findings are very different for Stargardt disease and CSNB, with Stargardt disease having classic fundus findings and characterized by a progressive course that can lead to severe central vision loss as atrophy develops. CSNB, on the other hand, is a stationary disease associated with mild reduction in visual acuity but with minimal foveomacular changes.…”

Section: Introductionmentioning

confidence: 98%

Sorting out Co-occurrence of Rare Monogenic Retinopathies: Stargardt Disease Co-existing with Congenital Stationary Night Blindness

Huynh

Jeffrey

Turriff

et al. 2014

Ophthalmic Genetics

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Congenital Stationary Night Blindness: Mutation Update and Clinical Variability

Cited by 24 publications

References 24 publications

Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease

Sorting out Co-occurrence of Rare Monogenic Retinopathies: Stargardt Disease Co-existing with Congenital Stationary Night Blindness

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Congenital Stationary Night Blindness: Mutation Update and Clinical Variability

Cited by 24 publications

References 24 publications

Dysregulation of Cav1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

Dysregulation of Cav1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

The Transduction Cascade in Retinal ON-Bipolar Cells: Signal Processing and Disease

Sorting out Co-occurrence of Rare Monogenic Retinopathies: Stargardt Disease Co-existing with Congenital Stationary Night Blindness

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Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2

Dysregulation of Ca_v1.4 channels disrupts the maturation of photoreceptor synaptic ribbons in congenital stationary night blindness type 2