X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

Molday, Robert S.; Kellner, Ulrich; Weber, Bernhard H. F.

doi:10.1016/j.preteyeres.2011.12.002

Cited by 271 publications

(299 citation statements)

References 189 publications

(311 reference statements)

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“…47,48 It is one of the most common inherited retinal disorders affecting macular function in males, with prevalence between 1 in 5000 to 20,000. 49 It is associated with mutations in the RS1 gene that encodes for retinoschisin, a secreted protein that is expressed in and tightly binds to the surface of photoreceptor and bipolar cells.…”

Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

“…It is present in both the inner and outer plexiform layers. 47,48 The foveal schisis is usually associated with moderate vision loss and is present in virtually all cases of the disease, 47 with only one recent case report describing an affected patient without this finding. 50 The peripheral schisis, which can predispose patients to more severe vision loss, is present in less than half of affected individuals.…”

Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

“…If inner retinal degeneration or breaks occur in conjunction with outer retina breaks, retinal detachment can occur. 47 Repair of these retinal detachments requires careful consideration of the detached inner retinal wall. Management options include performing an inner wall retinectomy or dissecting the posterior hyaloid off the inner retinal wall.…”

Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

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Evaluation and management of pediatric rhegmatogenous retinal detachment

Wenick¹,

Barañano²

2012

Saudi Journal of Ophthalmology

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Pediatric rhegmatogenous retinal detachments are rare, accounting for less than ten percent of all rhegmatogenous retinal detachments. While most retinal detachments in the adult population are related to posterior vitreous detachment, pediatric retinal detachment are often related to trauma or an underlying congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the often late presentation of the disease, and the high incidence of bilateral pathology in children all pose significant challenges in the management of these patients. We discuss the epidemiology of pediatric rhegmatogenous retinal detachment, review the genetic syndromes associated with a high incidence of retinal detachment, and examine other common causes of retinal detachment in this age group. We then outline an approach to evaluation and management and describe the expected outcomes of repair of retinal detachment in the pediatric population.

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Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

Section: X-linked Juvenile Retinoschisismentioning

confidence: 99%

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Evaluation and management of pediatric rhegmatogenous retinal detachment

Wenick¹,

Barañano²

2012

Saudi Journal of Ophthalmology

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“…The clinical manifestation is a pathological separation of retinal layers, leading to structural splitting and cavity (or "schisis") formation (10). Additionally, the bipolar cells show disorganization (11) and failure to maintain synaptic organization (9). Both XLRS patients and RS1 gene knockout mouse models (Rs1-KO) show similar phenotypes: schisis/splitting through retinal layers and synaptic transmission defects manifested as reduced b-wave amplitudes on the clinical electroretinogram ( Fig.…”

mentioning

confidence: 99%

Paired octamer rings of retinoschisin suggest a junctional model for cell–cell adhesion in the retina

Tolun

Vijayasarathy

Huang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Retinoschisin (RS1) is involved in cell-cell junctions in the retina, but is unique among known cell-adhesion proteins in that it is a soluble secreted protein. Loss-of-function mutations in RS1 lead to early vision impairment in young males, called X-linked retinoschisis. The disease is characterized by separation of inner retinal layers and disruption of synaptic signaling. Using cryo-electron microscopy, we report the structure at 4.1 Å, revealing double octamer rings not observed before. Each subunit is composed of a discoidin domain and a small N-terminal (RS1) domain. The RS1 domains occupy the centers of the rings, but are not required for ring formation and are less clearly defined, suggesting mobility. We determined the structure of the discoidin rings, consistent with known intramolecular and intermolecular disulfides. The interfaces internal to and between rings feature residues implicated in X-linked retinoschisis, indicating the importance of correct assembly. Based on this structure, we propose that RS1 couples neighboring membranes together through octamer-octamer contacts, perhaps modulated by interactions with other membrane components.retinoschisin | X-linked retinoschisis | discoidin domain | cryo-electron microscopy | single particle analysis T he structural integrity and functioning of tissues are highly dependent on cell-cell junctions. These are typically composed of two similar opposing layers of interacting proteins embedded as oligomers or arrays in the cellular membranes. For example, paired arrays of cadherins are found in adherens junctions and desmosomes (1); of claudins and occludins in tight junctions (2, 3); and of connexin channels in gap junctions (4). The back-to-back architecture of these junctions is fundamental to their adhesive function.The retina features another protein implicated in cell-cell adhesion, retinoschisin (RS1). RS1 is a 24-kDa protein expressed exclusively by photoreceptors and bipolar cells in the retina (5) and pineal gland (6). Loss-of-function mutants of RS1 lead to progressive visual impairment in a disease called X-linked retinoschisis (XLRS) (7-9). The clinical manifestation is a pathological separation of retinal layers, leading to structural splitting and cavity (or "schisis") formation (10). Additionally, the bipolar cells show disorganization (11) and failure to maintain synaptic organization (9). Both XLRS patients and RS1 gene knockout mouse models (Rs1-KO) show similar phenotypes: schisis/splitting through retinal layers and synaptic transmission defects manifested as reduced b-wave amplitudes on the clinical electroretinogram ( Fig. S1) (8, 12). RS1 gene therapy rescues the XLRS mouse phenotype (9, 13) and human RS1 gene therapy trials are underway (ClinicalTrials.gov: NCT02317887; NCT02416622).RS1 is secreted as a soluble disulfide bond-stabilized octamer (14, 15). Most of the monomer comprises a discoidin (DS) domain, a globular fold that is highly conserved over many proteins with diverse functions (16). Little progress has been made toward...

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“…This disease is caused by mutation(s) of the RS1 gene, which encodes for a protein (retinoschisin) that binds to the external membrane of photoreceptor and bipolar cells and plays a role in the structural integrity of the retinal layers. 1 In the first few decades of life cysticappearing (schitic) lesions are found in the macula, and central visual acuity is decreased. Clinically detectable peripheral retinoschisis, most commonly observed bilaterally in the inferior-temporal retina, is often found in XLRS.…”

mentioning

confidence: 99%