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Mutations in the KIF7 gene have been implicated in autosomal recessive conditions such as Joubert syndrome, acrocallosal syndrome, and fetal hydrolethalus, as well as in retinal degeneration and other ocular manifestations due to their effect on primary cilia. In this study, we report that the full-field electroretinogram (ERG) test showed non-recordable scotopic ERG responses, while photopic ERG responses were diminished bilaterally. This is a case report of a 62-year-old female patient with painless, progressive vision loss in both eyes. Fundus examination revealed a pale optic nerve head, vessel attenuation, and macular thinning without peripheral pigmentary changes. The full-field electroretinogram (ERG) test showed non-recordable scotopic ERG responses, while photopic ERG responses were diminished bilaterally. Based on these ocular findings, the patient was clinically diagnosed with retinitis pigmentosa (RP) sine pigmento. Genetic testing identified a pathogenic heterozygous mutation in the KIF7 gene with the variant c.61C>T (p.Arg21*). Our case suggests that this pathologic variant may be associated with RP sine pigmento. Further studies are warranted to better understand the role of the KIF7 gene in retinal dystrophies.
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The prevalence of retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, has been increasing globally and is linked to the aging population and improved life expectancy. These diseases are characterized by chronic, progressive neuronal damage or depletion of the photoreceptor cells in the retina, and limited effective treatment options are currently available. Mesenchymal stem cell-derived exosomes (MSC-EXOs) containing cytokines, growth factors, lipids, mRNA, and miRNA, which act as mediators of intercellular communication transferring bioactive molecules to recipient cells, offer an appealing, non-cellular nanotherapeutic approach for retinal degenerative diseases. However, treatment specificity is compromised due to their high heterogeneity in size, content, functional effects, and parental cellular source. To improve this, engineered MSC-EXOs with increased drug-loading capacity, targeting ability, and resistance to bodily degradation and elimination have been developed. This review summarizes the recent advances in miRNAs of MSC-EXOs as a treatment for retinal degeneration, discussing the strategies and methods for engineering therapeutic MSC-EXOs. Notably, to address the single functional role of engineered MSC-EXOs, we propose a novel concept called "Compound Engineered MSC-EXOs (Co-E-MSC-EXOs)" along with its derived potential therapeutic approaches. The advantages and challenges of employing Co-E-MSC-EXOs for retinal degeneration in clinical applications, as well as the strategies and issues related to them, are also highlighted.
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , Degeneración Retiniana , Humanos , Anciano , Exosomas/metabolismo , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Citocinas/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Retinitis Pigmentosa (RP) is an inherited retinal dystrophy (IRD) that causes progressive visual loss. Patients suffering from RP have a substantial influence on their everyday activities, social contacts, and jobs, lowering their quality of life. Frequent referral delays, as well as the lack of a standard therapy for the majority of patients, contribute to the significant unmet demand for RP. Any retinal injury has the potential to result in total blindness and visual impairment. Despite the fact that there is no cure for RP, people can manage it using rehabilitation programs and low-vision gadgets. The purpose of this research is to characterize the expanding treatment landscape for RP, as well as the justification for advanced therapy medicinal products (ATMPs). Vitamin A supplements can help prevent the sluggish visual loss caused by a prevalent kind of RP. The presence of visual purple in the rods and the underlying vascular choroid causes the retina to look purplish red. The major portion of the retina damaged is the rod photoreceptor electric cell; the development of diverse diseases is progressive. Because of the retina's accessibility, immunological privilege, and compartmentalization, hereditary retinal diseases are amenable to cell and gene therapy. Therapeutic techniques that attempt to rescue photoreceptors (gene therapies) require the existence of non-functional target cells, but other therapies (cell therapies) do not require the presence of live photoreceptors. To provide successful therapy choices for RP patients at all disease phases, the development pipeline must be continually diversified and advanced, as well as ongoing efforts to encourage early patient identification and quick diagnosis. Future research will focus on avoiding vision loss in genetic eye illnesses and assisting patients in regaining their eyesight. Retinal implants, cell therapies, supplementary medications, and gene therapies may become common treatments for reducing vision loss in the future.
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Background: Radix Salviae (Danshen)-Angelicae Sinensis Radix (Danggui)-Lycii Fructus (Gouqizi)-Rehmanniae Radix Praeparata (Shudihuang)-Ginkgo Folium (Yinxinye) (RALRG) are commonly used herbs in China that have shown positive effects on retinitis pigmentosa (RP). However, little research has been performed on the impact of RALRG and RP. Herein, this study aimed to predict the mechanism and potential components of RALRG in treating RP. Methods: The ingredients of RALRG were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP); the potential targets of RP and RALRG were obtained from TCMSP, GeneCards, and the Online Mendelian Inheritance in Man (OMIM) database. A protein-protein interaction (PPI) network was constructed to visualize PPIs. The functional enrichment was performed with the R program. A visual RALRG-RP-pathway pharmacology network was established by Cytoscape 3.9.1. Molecular docking was used to perform molecular docking and calculate the binding affinity. Results: A total of 132 effective active ingredients in RALRG with 248 target genes were screened; 92 intersection target genes were acquired from the intersection of RP- and RALRG-related genes. Gene Ontology (GO) enrichment indicated that these intersection targets were mainly involved in oxidative stress, metal ion response, and chemical stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the PI3K-AKT, cellular senescence, and MAPK signaling pathways were closely related to the therapy of RP. In addition, a potential pharmacology network for RALRG-RP-pathway was constructed. AKT1 and JUN were considered the primary targets. Luteolin, quercetin, and kaempferol were identified as the vital three active ingredients. Conclusions: RALRG was found to be the main regulator for oxidative stress and PI3K/AKT signaling pathways. Luteolin, quercetin, and kaempferol were three promising complementary ingredients for RP treatment. This study may provide a theoretical basis for applying RALRG to screen potential drugs for RP.
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Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates the transmembrane peptides into lipid bilayers, and the function of its cytoplasmic carboxyl terminus remains to be elucidated. In this study, an insertional mutation c.768insT in the C-terminal coding region of EMC3 was identified and associated with dominant IRDs in a five-generation family. This mutation caused a frameshift in the coding sequence and a gain of an additional 16 amino acid residues (p.L256F-fs-ext21) to form a helix structure in the C-terminus of the EMC3 protein. The mutation is heterozygous with an incomplete penetrance, and cosegregates in all patients examined. This finding indicates that the C-terminus of EMC3 is essential for EMC functions and that EMC3 may be a novel candidate gene for retinal degenerative diseases.
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PURPOSE: Stem cell therapy is a promising therapeutic approach for inherited retinal diseases (IRDs). This study aims to quantitatively examine the effectiveness and safety of stem cell therapy for patients with IRDs, including retinitis pigmentosa and Stargardt disease (STGD). METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library databases, and the ClinicalTrials.gov website. The latest retrieval time was August 20, 2023. The primary outcomes were rates and mean difference (MD) of best-corrected visual acuity (BCVA) improvement. Subgroup analyses were conducted according to administration routes and stem cell types. This study was registered with PROSPERO (CRD42022349271). RESULTS: Twenty-one prospective studies, involving 496 eyes (404 RP and 92 STGD) of 382 patients (306 RP and 76 STGD), were included in this study. For RP, the rate of BCVA improvement was 49% and 30% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months post-treatment (MD = - 0.12 logMAR, 95% CI .17 to - 0.06 logMAR; P < 0.001), while there was no significant difference at 12 months post-treatment (MD = -0.06 logMAR; 95% CI - 0.13 to 0.01 logMAR; P = 0.10). For STGD, the rate of BCVA improvement was 60% and 55% at 6 months and 12 months, respectively, and the BCVA was significantly improved in the operative eyes at 6 months (MD = - 0.14 logMAR, 95% CI - 0.22 to - 0.07 logMAR; P = 0.0002) and 12 months (MD = - 0.17 logMAR, 95% CI - 0.29 to - 0.04 logMAR; P = 0.01). Subgroup analyses showed suprachoroidal space injection of stem cells may be more efficient for RP. Eleven treated-related ocular adverse events from three studies and no related systemic adverse events were reported. CONCLUSIONS: This study suggests stem cell therapy may be effective and safe for patients with RP or STGD. The long-term vision improvement may be limited for RP patients. Suprachoroidal space injection of stem cells may be a promising administration route for RP patients. Limited by the low grade of evidence, large sample size randomized clinical trials are required in the future.
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Efusiones Coroideas , Retinitis Pigmentosa , Humanos , Estudios Prospectivos , Agudeza Visual , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.
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Distrofias de Conos y Bastones , Anomalías del Ojo , Amaurosis Congénita de Leber , Degeneración Macular , Distrofias Retinianas , Retinitis Pigmentosa , Humanos , Estudios Retrospectivos , Retina , Distrofias Retinianas/genética , Retinitis Pigmentosa/genética , Proteínas del Ojo/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
Purpose: This study aimed to develop a prediction model to classify RPE65-mediated inherited retinal disease (IRDs) based on protein secondary structure and to analyze phenotype-protein structure correlations of RPE65 missense variants in a Chinese cohort. Methods: Pathogenic or likely pathogenic missense variants of RPE65 were obtained from UniProt, ClinVar, and HGMD databases. The three-dimensional structure of RPE65 was retrieved from the Protein Data Bank (PDB) and modified with Pymol software. A novel prediction model was developed using LASSO regression and multivariate logistic regression to identify RPE65-associated IRDs. A total of 21 Chinese probands with RPE65 variants were collected to analyze phenotype-protein structure correlations of RPE65 missense variants. Results: The study found that both pathogenic and population missense variants were associated with structural features of RPE65. Pathogenic variants were linked to sheet, ß-sheet, strands, ß-hairpins, Fe2+ (iron center), and active site cavity, while population variants were related to helix, loop, helices, and helix-helix interactions. The novel prediction model showed accuracy and confidence in predicting the disease type of RPE65 variants (AUC = 0.7531). The study identified 25 missense variants in Chinese patients, accounting for 72.4% of total mutations. A significant correlation was observed between clinical characteristics of RPE65-associated IRDs and changes in amino acid type, specifically for missense variants of F8 (H68Y, P419S). Conclusion: The study developed a novel prediction model based on the protein structure of RPE65 and investigated phenotype-protein structure correlations of RPE65 missense variants in a Chinese cohort. The findings provide insights into the precise diagnosis of RPE65-mutated IRDs.
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Amaurosis Congénita de Leber , Enfermedades de la Retina , cis-trans-Isomerasas , Humanos , Amaurosis Congénita de Leber/genética , Linaje , Retina/patología , Enfermedades de la Retina/genética , Mutación Missense , cis-trans-Isomerasas/genética , Fenotipo , Conformación ProteicaRESUMEN
Retinal angiomatous proliferation (RAP) and other types of choroidal neovascularization (CNV) are very rarely reported in patients with retinitis pigmentosa (RP). We present a case report of a 91-year-old patient with an obvious RP phenotype, who presented with a sudden onset of vision worsening and metamorphopsia in the left eye. Genetic testing on the UK inherited retinal disease panel did not identify a pathogenic variant. Multimodal imaging comprising optical coherence tomography (OCT), OCT angiography, and fluorescein and indocyanine green angiography showed a RAP lesion in the left macula. The patient received three treatments of monthly injections of aflibercept, with excellent morphological and functional outcomes. Taking into account the patient's age at presentation of the RAP lesion, it is not clear whether the RAP was associated or coincidental with RP. This case report highlights the importance of possessing an awareness that RAP lesions can occur in RP. Moreover, due to a good response and potential safety concerns with continuous anti-VEGF injections in RP patients, a pro re nata (PRN) regimen might be the safest option.
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Degeneración Macular , Neovascularización Retiniana , Retinitis Pigmentosa , Humanos , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/genética , Angiografía con Fluoresceína/métodos , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/genética , Degeneración Macular/patología , Retina/patología , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Proliferación CelularRESUMEN
Prime editing (PE) is a novel, double-strand break (DSB)-independent gene editing technology that represents an exciting avenue for the treatment of inherited retinal diseases (IRDs). Given the extensive and heterogenous nature of the 280 genes associated with IRDs, genome editing has presented countless complications. However, recent advances in genome editing technologies have identified PE to have tremendous potential, with the capability to ameliorate small deletions and insertions in addition to all twelve possible transition and transversion mutations. The current PE system is based on the fusion of the Streptococcus pyogenes Cas9 (SpCas9) nickase H840A mutant and an optimized Moloney murine leukemia virus (MMLV) reverse-transcriptase (RT) in conjunction with a PE guide RNA (pegRNA). In this study, we developed a prime editor based on the avian myeloblastosis virus (AMV)-RT and showed its applicability for the installation of the PRPH2 c.828+1G>A mutation in HEK293 cells.
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Virus de la Mieloblastosis Aviar , ADN Polimerasa Dirigida por ARN , Humanos , Animales , Ratones , ADN Polimerasa Dirigida por ARN/genética , ADN Polimerasa Dirigida por ARN/metabolismo , Virus de la Mieloblastosis Aviar/genética , Virus de la Mieloblastosis Aviar/metabolismo , Células HEK293 , Edición Génica , Virus de la Leucemia Murina de Moloney/genética , Virus de la Leucemia Murina de Moloney/metabolismo , Sistemas CRISPR-CasRESUMEN
The mouse and human retina contain three major Crumbs homologue-1 (CRB1) isoforms. CRB1-A and CRB1-B have cell-type-specific expression patterns making the choice of gene augmentation strategy unclear. Gene editing may be a viable alternative for the amelioration of CRB1-associated retinal degenerations. To assess the prevalence and spectrum of CRB1-associated pathogenic variants amenable to base and prime editing, we carried out an analysis of the Leiden Open Variation Database. Editable variants accounted for 54.5% for base editing and 99.8% for prime editing of all CRB1 pathogenic variants in the Leiden Open Variation Database. The 10 most common editable pathogenic variants for CRB1 accounted for 34.95% of all pathogenic variants, with the c.2843G>A, p.(Cys948Tyr) being the most common editable CRB1 variant. These findings outline the next step toward developing base and prime editing therapeutics as an alternative to gene augmentation for the amelioration of CRB1-associated retinal degenerations.
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Degeneración Retiniana , Humanos , Animales , Ratones , Degeneración Retiniana/genética , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Mutación , Retina/metabolismo , Isoformas de Proteínas/genética , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismoRESUMEN
Mutations in the Crumbs-homologue-1 (CRB1) gene lead to a spectrum of severe inherited retinal diseases, including retinitis pigmentosa (RP). The establishment of a genotype-phenotype correlation in CRB1 patients has been difficult due to the substantial variability and phenotypic overlap between CRB1-associated diseases. This phenotypic modulation may be due to several factors, including genetic modifiers, deep intronic mutations, isoform diversity, and copy number variations. Induced pluripotent stem cell (iPSC)-derived patient retinal organoids are novel tools that can provide sensitive, quantitative, and scalable phenotypic assays. CRB1 RP patient iPSC-derived retinal organoids have shown reproducible phenotypes compared to healthy retinal organoids. However, having genetically defined iPSC isogenic controls that take into account potential phenotypic modulation is crucial. In this study, we generated iPSC from an early-onset CRB1 patient and developed a correction strategy for the c.2480G>T, p.(Gly827Val) CRB1 mutation using CRISPR/Cas9-mediated homology-directed repair.
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Células Madre Pluripotentes Inducidas , Retinitis Pigmentosa , Humanos , Sistemas CRISPR-Cas/genética , Variaciones en el Número de Copia de ADN , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/terapia , Mutación , Proteínas del Ojo/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genéticaRESUMEN
Purpose: To describe the phenotypic variations in family members of patients with retinitis pigmentosa (RP) with different modes of inheritance and to assess the ocular abnormalities in RP families. Methods: A descriptive analysis of three types of inheritance of RP was carried out, where 64 family members were examined at a tertiary eye care center, South India. They underwent comprehensive eye examination, fundus photography, fundus autofluorescence (FAF), full-field electroretinogram (FFERG), and spectral domain optical coherence tomography (SD-OCT). Analysis was performed between mild and severe forms of abnormalities to delineate retinal structural and functional defects in RP families. Results: The mean age was 38.55 ± 17.95 years. Males were 48.4%. In autosomal recessive and X-linked recessive groups, 74.2% and 77.3%, respectively, were asymptomatic, whereas in autosomal dominant group, 27.3% were asymptomatic. The proportion of the cases with abnormalities in all three groups was higher on ERG (59.6%), followed by OCT (57.5%), visual acuity (43.7%), peripheral FAF (23.5%), and macular FAF (11.8%). However, these abnormalities and the clinical pictures of the family members had no statistical difference across the three groups of inheritance. Conclusion: Structural and functional retinal alterations were noted in four out of five asymptomatic members, suggesting the need for careful screening of RP families and the pressing need for pre-test (genetic) counseling.
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Retinitis Pigmentosa , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genética , Retina/diagnóstico por imagen , Electrorretinografía , Técnicas de Diagnóstico Oftalmológico , Familia , Tomografía de Coherencia ÓpticaRESUMEN
To report the spectrum of Leber congenital amaurosis (LCA) associated genes in a large German cohort and to delineate their associated phenotype. Local databases were screened for patients with a clinical diagnosis of LCA and for patients with disease-causing variants in known LCA-associated genes independent of their clinical diagnosis. Patients with a mere clinical diagnosis were invited for genetic testing. Genomic DNA was either analyzed in a diagnostic-genetic or research setup using various capture panels for syndromic and non-syndromic IRD (inherited retinal dystrophy) genes. Clinical data was obtained mainly retrospectively. Patients with genetic and phenotypic information were eventually included. Descriptive statistical data analysis was performed. A total of 105 patients (53 female, 52 male, age 3-76 years at the time of data collection) with disease-causing variants in 16 LCA-associated genes were included. The genetic spectrum displayed variants in the following genes: CEP290 (21%), CRB1 (21%), RPE65 (14%), RDH12 (13%), AIPL1 (6%), TULP1 (6%), and IQCB1 (5%), and few cases harbored pathogenic variants in LRAT, CABP4, NMNAT1, RPGRIP1, SPATA7, CRX, IFT140, LCA5, and RD3 (altogether accounting for 14%). The most common clinical diagnosis was LCA (53%, 56/105) followed by retinitis pigmentosa (RP, 40%, 42/105), but also other IRDs were seen (cone-rod dystrophy, 5%; congenital stationary night blindness, 2%). Among LCA patients, 50% were caused by variants in CEP290 (29%) and RPE65 (21%), whereas variants in other genes were much less frequent (CRB1 11%, AIPL1 11%, IQCB1 9%, and RDH12 7%, and sporadically LRAT, NMNAT1, CRX, RD3, and RPGRIP1). In general, the patients showed a severe phenotype hallmarked by severely reduced visual acuity, concentric narrowing of the visual field, and extinguished electroretinograms. However, there were also exceptional cases with best corrected visual acuity as high as 0.8 (Snellen), well-preserved visual fields, and preserved photoreceptors in spectral domain optical coherence tomography. Phenotypic variability was seen between and within genetic subgroups. The study we are presenting pertains to a considerable LCA group, furnishing valuable comprehension of the genetic and phenotypic spectrum. This knowledge holds significance for impending gene therapeutic trials. In this German cohort, CEP290 and CRB1 are the most frequently mutated genes. However, LCA is genetically highly heterogeneous and exhibits clinical variability, showing overlap with other IRDs. For any therapeutic gene intervention, the disease-causing genotype is the primary criterion for treatment access, but the clinical diagnosis, state of the retina, number of to be treated target cells, and the time point of treatment will be crucial.
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Amaurosis Congénita de Leber , Nicotinamida-Nucleótido Adenililtransferasa , Masculino , Femenino , Humanos , Amaurosis Congénita de Leber/genética , Estudios Retrospectivos , Mutación , Proteínas del Ojo/genética , Genotipo , Análisis Mutacional de ADN , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Nicotinamida-Nucleótido Adenililtransferasa/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Oxidorreductasas de Alcohol/genéticaRESUMEN
Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of disorders with progressive loss of photoreceptor and pigment epithelial function. Nineteen unrelated Polish probands clinically diagnosed with nonsyndromic RP were recruited to this study. We used whole-exome sequencing (WES) to identify potential pathogenic gene variants in molecularly undiagnosed RP patients, as a molecular re-diagnosis after having performed targeted NGS in the past. Targeted NGS allowed for identification of the molecular background in only 5 out of 19 patients. Fourteen patients who remained unsolved despite the targeted NGS were subjected to WES. WES revealed potentially causative variants in RP-related genes in another 12 patients. Together, NGS methods revealed the coexistence of causal variants affecting distinct RP genes in 17 out of 19 RP families, with a very high efficiency of 89%. With the improvement of NGS methods, including higher sequencing depth, broader target enrichment, and better bioinformatic analysis capabilities, the ratio of identified causal gene variants has significantly increased. Therefore, it is important to consider repeating high-throughput sequencing analysis in those patients in whom the previously performed NGS did not reveal any pathogenic variants. The study confirmed the efficiency and clinical utility of re-diagnosis with WES in molecularly undiagnosed RP patients.
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PURPOSE: To analyze publication trends for the past 20 years and identify potential research trends in the retinitis pigmentosa (RP) research field. METHODS: We extracted data from the Web of Science Core Collection and conducted a bibliometric analysis. All records related to RP from 2002 to 2021 were analyzed. The co-occurrence maps of keywords were generated by VOSviewer v.1.6.17 to identify knowledge structure and research trends in the RP research field. RESULTS: Totally 1976 publications from 2002 to 2021 were included in this study. The United States ranked first in the number of publications, citations and H-index. INVESTIGATIVE OPHTHALMOLOGY VISUAL SCIENCE was the most prolific journal in the RP research field. LEAGUE OF EUROPEAN RESEARCH UNIVERSITIES LERU had the greatest output in the RP research field. Tsang SH contributed to the highest number of publications in the RP research field. All keywords were divided into three clusters: (1) gene mutations, (2) pathophysiological changes, and (3) diagnosis and management in the RP research field. Average appearing years of keywords were evaluated and most of the recently appearing keywords focused on the pathophysiological changes. CONCLUSIONS: By bibliometric analysis, the knowledge structure of RP research field was identified. It may help clinicians to comprehensively understand the hotspots and guide the research trends in the RP research field.
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Oftalmología , Retinitis Pigmentosa , Humanos , Bibliometría , Mutación , UniversidadesRESUMEN
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy. There are three main characteristics of RP: night blindness, retinal pigmentation, and visual field constriction. Among these three features, night blindness was the first to be discovered, which could be dated back to the ancient Egyptians at around 1500 BC. However, the night blindness described at that time was most likely associated with vitamin A deficiency rather than RP. Retinitis pigmentosa was first described in cadaver anatomic dissection before the invention of the ophthalmoscope. However, it was not linked to RP or night blindness. It was not until the invention of the ophthalmoscope that ophthalmologists could truly look into the eye and correlate the retinal pigmentation with clinical symptoms, such as night blindness and visual field constriction. In 1983, at a RP workshop that gathered together many experts, a consensus was reached regarding the terminology and guidelines for the diagnosis of RP. In this chapter, we will introduce the history and discovery of RP along with its characteristics.
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Ceguera Nocturna , Retinitis Pigmentosa , Humanos , Retinitis Pigmentosa/diagnósticoRESUMEN
Electroretinogram (ERG) captures the electrical responses of photoreceptors, the summation of action potentials from all neurons in the retina elicited by illumination. ERG testing is an incredibly useful tool in obtaining more specific information regarding a retinal dystrophy. Specifically, ERGs are typically used to test photoreceptors and inner retinal function in humans and animals, to diagnose retinal dystrophies, and to monitor disease progression. In this chapter, we will introduce the components of ERGs and the standard ERG protocols for clinical examination. We will also introduce the various specialized ERG tests, which can help to differentiate retinitis pigmentosa (RP) from other retinal disorders. Lastly, we will elaborate on how to use ERGs to predict visual prognosis in RP.
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Retinitis Pigmentosa , Humanos , Retinitis Pigmentosa/diagnóstico , Regulador Transcripcional ERG , ElectrorretinografíaRESUMEN
Inherited retinal diseases (IRDs) encompass a large heterogeneous group of rare blinding disorders whose etiology originates from mutations in the 280 genes identified to date. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems represent a promising avenue for the treatment of IRDs, as exemplified by FDA clinical trial approval of EDIT-101 (AGN-151587), which removes a deep intronic variant in the CEP290 gene that causes Leber congenital amaurosis (LCA) type 10. Prime editing is a novel double-strand break (DSB) independent CRISPR/Cas system which has the potential to correct all 12 possible transition and transversion mutations in addition to small deletions and insertions. Here, as a proof-of-concept study, we describe a methodology using prime editing for the in vitro installation and correction of the classical Pde6brd10 c.1678C > T (p.Arg560Cys) mutation which causes autosomal recessive retinitis pigmentosa (RP) in mice.
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Enfermedades de la Retina , Ratones , Animales , Prueba de Estudio Conceptual , MutaciónRESUMEN
MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.