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International Journal of Molecular... Apr 2022Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in... (Review)
Review
Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in blindness in bilateral eyes. Various photoreceptor cell death types and pathological phenotypic changes that have been disclosed in RP demand in-depth research of its pathogenic mechanism that may account for inter-patient heterogeneous responses to mainstream drug treatment. As the primary method for studying the genetic characteristics of RP, molecular biology has been widely used in disease diagnosis and clinical trials. Current technology iterations, such as gene therapy, stem cell therapy, and optogenetics, are advancing towards precise diagnosis and clinical applications. Specifically, technologies, such as effective delivery vectors, CRISPR/Cas9 technology, and iPSC-based cell transplantation, hasten the pace of personalized precision medicine in RP. The combination of conventional therapy and state-of-the-art medication is promising in revolutionizing RP treatment strategies. This article provides an overview of the latest research on the pathogenesis, diagnosis, and treatment of retinitis pigmentosa, aiming for a convenient reference of what has been achieved so far.
Topics: Genetic Therapy; Humans; Induced Pluripotent Stem Cells; Pathology, Molecular; Photoreceptor Cells; Retinitis Pigmentosa
PubMed: 35563274
DOI: 10.3390/ijms23094883 -
Medecine Sciences : M/S 2020Retinitis pigmentosa is the most common blinding inherited retinal dystrophy. Gene therapy is a burgeoning revolutionary approach that paves the way to treatment of... (Review)
Review
Retinitis pigmentosa is the most common blinding inherited retinal dystrophy. Gene therapy is a burgeoning revolutionary approach that paves the way to treatment of previously incurable diseases. At the end of 2017 and 2018, a gene therapy, Luxturna, obtained a marketing authorization by respectively the FDA (Food and Drug Administration) and the EMA (European Medicines Agency). This treatment, with proven efficacy, is available to patients with Leber congenital amaurosis and retinitis pigmentosa associated with bi-allelic mutations of the RPE 65 gene. In this paper, we present the current advances in gene therapy for retinitis pigmentosa and discuss the technological, economic and ethical challenges to overcome for gene therapy to improve medical practices.
Topics: Genetic Association Studies; Genetic Therapy; Humans; Mutation; Practice Patterns, Physicians'; Quality Improvement; Retinitis Pigmentosa
PubMed: 32614312
DOI: 10.1051/medsci/2020095 -
Clinical Genetics Aug 2013Retinitis pigmentosa (RP) is a heterogeneous set of inherited retinopathies with many disease-causing genes, many known mutations, and highly varied clinical... (Review)
Review
Retinitis pigmentosa (RP) is a heterogeneous set of inherited retinopathies with many disease-causing genes, many known mutations, and highly varied clinical consequences. Progress in finding treatments is dependent on determining the genes and mutations causing these diseases, which includes both gene discovery and mutation screening in affected individuals and families. Despite the complexity, substantial progress has been made in finding RP genes and mutations. Depending on the type of RP, and the technology used, it is possible to detect mutations in 30-80% of cases. One of the most powerful approaches to genetic testing is high-throughput 'deep sequencing', that is, next-generation sequencing (NGS). NGS has identified several novel RP genes but a substantial fraction of previously unsolved cases have mutations in genes that are known causes of retinal disease but not necessarily RP. Apparent discrepancy between the molecular defect and clinical findings may warrant reevaluation of patients and families. In this review, we summarize the current approaches to gene discovery and mutation detection for RP, and indicate pitfalls and unsolved problems. Similar considerations apply to other forms of inherited retinal disease.
Topics: Genetic Association Studies; Genomics; Humans; Mutation; Retinitis Pigmentosa
PubMed: 23701314
DOI: 10.1111/cge.12203 -
Progress in Retinal and Eye Research Sep 2018Retinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading... (Review)
Review
Retinitis pigmentosa (RP) encompasses a group of inherited retinal dystrophies characterized by the primary degeneration of rod and cone photoreceptors. RP is a leading cause of visual disability, with a worldwide prevalence of 1:4000. Although the majority of RP cases are non-syndromic, 20-30% of patients with RP also have an associated non-ocular condition. RP typically manifests with night blindness in adolescence, followed by concentric visual field loss, reflecting the principal dysfunction of rod photoreceptors; central vision loss occurs later in life due to cone dysfunction. Photoreceptor function measured with an electroretinogram is markedly reduced or even absent. Optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging show a progressive loss of outer retinal layers and altered lipofuscin distribution in a characteristic pattern. Over the past three decades, a vast number of disease-causing variants in more than 80 genes have been associated with non-syndromic RP. The wide heterogeneity of RP makes it challenging to describe the clinical findings and pathogenesis. In this review, we provide a comprehensive overview of the clinical characteristics of RP specific to genetically defined patient subsets. We supply a unique atlas with color fundus photographs of most RP subtypes, and we discuss the relevant considerations with respect to differential diagnoses. In addition, we discuss the genes involved in the pathogenesis of RP, as well as the retinal processes that are affected by pathogenic mutations in these genes. Finally, we review management strategies for patients with RP, including counseling, visual rehabilitation, and current and emerging therapeutic options.
Topics: Diagnosis, Differential; Diagnostic Techniques, Ophthalmological; Electroretinography; Eye Proteins; Genotype; Humans; Mutation; Night Blindness; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Tomography, Optical Coherence; Vision Disorders
PubMed: 29597005
DOI: 10.1016/j.preteyeres.2018.03.005 -
Revue Medicale de Liege Feb 2020Retinitis pigmentosa is the most frequent hereditary dystrophy of the retina, with a global prevalence of 1/4.000. The underlying mechanism involves progressive loss,...
Retinitis pigmentosa is the most frequent hereditary dystrophy of the retina, with a global prevalence of 1/4.000. The underlying mechanism involves progressive loss, first of the rod photoreceptor cells, followed by the cone photoreceptor cells. Finally, complete blindness may occur. Genetic transmission is known but most cases are sporadic. Few effective treatments exist nowadays and hence regular follow-up is required in a revalidation center.
Topics: Humans; Retina; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa
PubMed: 32030928
DOI: No ID Found -
Orphanet Journal of Rare Diseases Oct 2006Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus... (Review)
Review
Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis).
Topics: Adolescent; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Metabolic Diseases; Nervous System Diseases; Night Blindness; Pregnancy; Prenatal Diagnosis; Prognosis; Retinal Rod Photoreceptor Cells; Retinitis Pigmentosa; Rhodopsin; Sensation Disorders; Syndrome
PubMed: 17032466
DOI: 10.1186/1750-1172-1-40 -
Nature Medicine Mar 2020Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people....
Retinal gene therapy has shown great promise in treating retinitis pigmentosa (RP), a primary photoreceptor degeneration that leads to severe sight loss in young people. In the present study, we report the first-in-human phase 1/2, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 patients over up to 6 months of follow-up (https://clinicaltrials.gov/: NCT03116113). The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness. Apart from steroid-responsive subretinal inflammation in patients at the higher doses, there were no notable safety concerns after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. Visual field improvements beginning at 1 month and maintained to the last point of follow-up were observed in six patients.
Topics: Adult; Eye Proteins; Genetic Diseases, X-Linked; Genetic Therapy; Humans; Middle Aged; Mutation; Retina; Retinitis Pigmentosa; Young Adult
PubMed: 32094925
DOI: 10.1038/s41591-020-0763-1 -
Molecular Genetics & Genomic Medicine Mar 2020This study aimed to identify the gene variants and molecular etiologies in 76 unrelated Chinese families with retinitis pigmentosa (RP).
BACKGROUND
This study aimed to identify the gene variants and molecular etiologies in 76 unrelated Chinese families with retinitis pigmentosa (RP).
METHODS
In total, 76 families with syndromic or nonsyndromic RP, diagnosed on the basis of clinical manifestations, were recruited for this study. Genomic DNA samples from probands were analyzed by targeted panels or whole exome sequencing. Bioinformatics analysis, Sanger sequencing, and available family member segregation were used to validate sequencing data and confirm the identities of disease-causing genes.
RESULTS
The participants enrolled in the study included 62 families that exhibited nonsyndromic RP, 13 that exhibited Usher syndrome, and one that exhibited Bardet-Biedl syndrome. We found that 43 families (56.6%) had disease-causing variants in 15 genes, including RHO, PRPF31, USH2A, CLRN1, BBS2, CYP4V2, EYS, RPE65, CNGA1, CNGB1, PDE6B, MERTK, RP1, RP2, and RPGR; moreover, 12 families (15.8%) had only one heterozygous variant in seven autosomal recessive RP genes, including USH2A, EYS, CLRN1, CERKL, RP1, CRB1, and SLC7A14. We did not detect any variants in the remaining 21 families (27.6%). We also identified 67 potential pathogenic gene variants, of which 24 were novel.
CONCLUSION
The gene variants identified in this study expand the variant frequency and spectrum of RP genes; moreover, the identification of these variants supplies foundational clues for future RP diagnosis and therapy.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Genetic Testing; Humans; Male; Middle Aged; Retinitis Pigmentosa; Exome Sequencing
PubMed: 31960602
DOI: 10.1002/mgg3.1131 -
Indian Journal of Ophthalmology Mar 2013
Topics: Adult; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; India; Male; Morbidity; Retinitis Pigmentosa
PubMed: 23514641
DOI: 10.4103/0301-4738.109372 -
Asia-Pacific Journal of Ophthalmology... 2016Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative... (Review)
Review
Retinitis pigmentosa is the most common form of hereditary retinal degeneration causing blindness. Great progress has been made in the identification of the causative genes. Gene diagnosis will soon become an affordable routine clinical test because of the wide application of next-generation sequencing. Gene-based therapy provides hope for curing the disease. Investigation into the molecular pathways from mutation to rod cell death may reveal targets for developing new treatment. Related progress with existing systematic review is briefly summarized so that readers may find the relevant references for in-depth reading. Future trends in the study of retinitis pigmentosa are also discussed.
Topics: Animals; Clinical Trials as Topic; Cone-Rod Dystrophies; Disease Management; Disease Models, Animal; Gene Expression Profiling; Genetic Therapy; High-Throughput Nucleotide Sequencing; Humans; Mutation; Retinal Degeneration; Retinitis Pigmentosa; Stem Cell Transplantation
PubMed: 27488069
DOI: 10.1097/APO.0000000000000227