-
Cold Spring Harbor Perspectives in... Sep 2023X-linked retinoschisis (XLRS) is an inherited vitreoretinal dystrophy causing visual impairment in males starting at a young age with an estimated prevalence of 1:5000... (Review)
Review
X-linked retinoschisis (XLRS) is an inherited vitreoretinal dystrophy causing visual impairment in males starting at a young age with an estimated prevalence of 1:5000 to 1:25,000. The condition was first observed in two affected brothers by Josef Haas in 1898 and is clinically diagnosed by characteristic intraretinal cysts arranged in a petaloid "spoke-wheel" pattern centered in the macula. When clinical electroretinogram (ERG) testing began in the 1960s, XLRS was noted to have a characteristic reduction of the dark-adapted b-wave amplitude despite normal or usually nearly normal a-wave amplitudes, which became known as the "electronegative ERG response" of XLRS disease. The causative gene, , was identified on the X-chromosome in 1997 and led to understanding the molecular and cellular basis of the condition, discerning the structure and function of the retinoschisin protein, and generating XLRS murine models. Along with parallel development of gene delivery vectors suitable for targeting retinal diseases, successful gene augmentation therapy was demonstrated by rescuing the XLRS phenotype in mouse. Two human phase I/II therapeutic XLRS gene augmentation studies were initiated; and although these did not yield definitive improvement in visual function, they gave significant new knowledge and experience, which positions the field for further near-term clinical testing with enhanced, next-generation gene therapy for XLRS patients.
Topics: Male; Humans; Animals; Mice; Retinoschisis; Mutation; Electroretinography; Phenotype; Genetic Therapy; Eye Proteins; Retina
PubMed: 36690462
DOI: 10.1101/cshperspect.a041288 -
Seminars in Pediatric Neurology May 2017In this article, we review the following 3 common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy.... (Review)
Review
In this article, we review the following 3 common juvenile macular degenerations: Stargardt disease, X-linked retinoschisis, and Best vitelliform macular dystrophy. These are inherited disorders that typically present during childhood, when vision is still developing. They are sufficiently common that they should be included in the differential diagnosis of visual loss in pediatric patients. Diagnosis is secured by a combination of clinical findings, optical coherence tomography imaging, and genetic testing. Early diagnosis promotes optimal management. Although there is currently no definitive cure for these conditions, therapeutic modalities under investigation include pharmacologic treatment, gene therapy, and stem cell transplantation.
Topics: Child; Humans; Macula Lutea; Macular Degeneration; Retinoschisis; Stargardt Disease; Vitelliform Macular Dystrophy
PubMed: 28941524
DOI: 10.1016/j.spen.2017.05.005 -
Advances in Experimental Medicine and... 2018X-linked juvenile retinoschisis (XLRS) occurs exclusively in males and is characterized by visual loss that begins in early childhood; patients are usually school-age... (Review)
Review
X-linked juvenile retinoschisis (XLRS) occurs exclusively in males and is characterized by visual loss that begins in early childhood; patients are usually school-age and are experiencing visual disturbances, especially in reading. The prevalence is estimated to be 1 in 5000-25,000 men, worldwide. XLRS has complete penetrance but variable expressivity. Carrier females generally remain asymptomatic.
Topics: Child; Child, Preschool; Female; Genetic Diseases, X-Linked; Humans; Male; Retinoschisis
PubMed: 30578483
DOI: 10.1007/978-3-319-95046-4_10 -
Clinical & Experimental Optometry Sep 2020Retinoschisis can be found in the fovea or the retinal periphery, either of which may be present in isolation, or in conjunction with each other. Foveal schisis may be... (Review)
Review
Retinoschisis can be found in the fovea or the retinal periphery, either of which may be present in isolation, or in conjunction with each other. Foveal schisis may be congenital, acquired, or secondary to an associated ocular pathology such as optic pit, glaucoma, or pathological myopia. The visual acuity is dependent on the cause of the schisis and appropriate treatment is variable based on likelihood for progression and visual impact. There are many useful considerations and tools for evaluation and monitoring that can be used to determine the aetiology and prognosis of these retinal findings. Retinoschisis is a diagnosis of exclusion, and pathology must be ruled out to accurately make the diagnosis. A review of two cases and following discussion summarises the various types, manifestations, presentations, and complications of retinoschisis and their evaluation, management, and appropriate monitoring or treatment. These cases lead a dialogue on the presentation and aetiology of retinoschisis, important considerations for differential diagnoses, and appropriate management.
Topics: Fovea Centralis; Humans; Retinoschisis; Tomography, Optical Coherence; Visual Acuity
PubMed: 31663163
DOI: 10.1111/cxo.12977 -
Retina (Philadelphia, Pa.) Jan 2016
Topics: Endotamponade; Epiretinal Membrane; Female; Fluorocarbons; Humans; Male; Myopia, Degenerative; Retinoschisis; Vitrectomy
PubMed: 26702607
DOI: 10.1097/IAE.0000000000000915 -
Indian Journal of Ophthalmology Oct 2019
Topics: Humans; Male; Middle Aged; Ophthalmoscopy; Retina; Retinoschisis; Visual Acuity
PubMed: 31546543
DOI: 10.4103/ijo.IJO_193_19 -
Journal of Forensic Sciences Nov 2017
Topics: Algorithms; Craniocerebral Trauma; Humans; Infant; Retinal Hemorrhage; Retinoschisis
PubMed: 29152800
DOI: 10.1111/1556-4029.13630 -
Asia-Pacific Journal of Ophthalmology... 2018We present an updated clinical review of the pathophysiology, progression, and current treatments in pediatric patients with congenital X-linked retinoschisis (CXLRS).... (Review)
Review
We present an updated clinical review of the pathophysiology, progression, and current treatments in pediatric patients with congenital X-linked retinoschisis (CXLRS). CXLRS is an X-linked inherited retinal degeneration characterized by splitting of the superficial layers of the retina. Most recent classification divides CXLRS into 4 distinct clinical phenotypes: type 1, foveal; type 2, foveolamellar; type 3, complex; and type 4, foveoperipheral. The majority of retinoschisis cavities remain stable throughout life and may spontaneously collapse. However, a select number of patients progress to macula-involving peripheral retinoschisis, rhegmatogenous, and combined tractional-rhegmatogenous detachments that require further intervention. Although several advances have been made over the past several decades, medical therapy remains limited to case series‒based carbonic anhydrase therapy and prophylactic laser retinopexy. Recent advances in genetic-based clinical trials with the retinoschisis gene are promising. Vitreoretinal surgical approaches remain complex, case-based, and require careful planning depending on the configuration and location of the retinoschisis cavity.
Topics: Diagnostic Imaging; Disease Management; Genetic Testing; Genetic Therapy; Humans; Retinoschisis
PubMed: 29633586
DOI: 10.22608/APO.201803 -
Survey of Ophthalmology 2022Degenerative retinoschisis is a common condition characterized by elevation of the inner layers of the peripheral retina. While uncomplicated retinoschisis (i.e., with... (Review)
Review
Degenerative retinoschisis is a common condition characterized by elevation of the inner layers of the peripheral retina. While uncomplicated retinoschisis (i.e., with no associated retinal layer breaks) is almost invariably a benign process, retinal detachment associated with isolated outer layer breaks (termed schisis-detachment) is fairly common. Historically, schisis-detachment has been treated with a variety of interventions, ranging from retinopexy to intraocular surgery. Based on published descriptions of the natural history of the disease, these interventions are likely unnecessary in many cases and may place the patient's vision at unnecessary risk. Progressive symptomatic schisis-related retinal detachment, on the other hand, is a vision threatening condition that requires intervention. While clinical examination remains the mainstay of diagnosis, recent advances in multimodal imaging can provide supplemental information in subtle cases and may prove valuable for long-term disease monitoring. When evaluating patients with peripheral retinal elevation, it is important for ophthalmologists to make an accurate diagnosis and to understand the risk-benefit ratio associated with intervention. Thus, we summarize the current literature on the natural history, clinical and imaging diagnosis, and surgical management of degenerative retinoschisis and its related complications.
Topics: Humans; Retina; Retinal Detachment; Retinal Perforations; Retinoschisis
PubMed: 34896193
DOI: 10.1016/j.survophthal.2021.12.004 -
BMC Research Notes May 2021Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no...
OBJECTIVE
Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein-protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship.
RESULT
Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.
Topics: Animals; Blindness; Eye Proteins; Genetic Diseases, X-Linked; Humans; Mice; Mutation; Nervous System Diseases; Retina; Retinal Degeneration; Retinoschisis; Spasms, Infantile
PubMed: 34039417
DOI: 10.1186/s13104-021-05617-5