Gene Therapy for Color Blindness.
Authors: Hassall MM, Barnard AR, MacLaren RE
Abstract
Achromatopsia is a rare congenital cause of vision loss due to isolated cone photoreceptor dysfunction. The most common underlying genetic mutations are autosomal recessive changes in CNGA3, CNGB3, GNAT2, PDE6H, PDE6C, or ATF6. Animal models of Cnga3, Cngb3, and Gnat2 have been rescued using AAV gene therapy; showing partial restoration of cone electrophysiology and integration of this new photopic vision in reflexive and behavioral visual tests. Three gene therapy phase I/II trials are currently being conducted in human patients in the USA, the UK, and...
Source: The Yale Journal of Biology and Medicine - December 22, 2017 Category: Universities & Medical Training Tags: Yale J Biol Med Source Type: research
Diagnosis and Treatment Options for Achromatopsia: A Review of the Literature
Achromatopsia is an inherited retinal disease that affects the cone cell function. It is a genetic dysfunction of all types of cones1 and is usually an autosomal-recessive disease that affects 1:30,000 to 1:50,000 births. It is characterized by presentation at birth or early infancy with pendular nystagmus, poor visual acuity, lack of color vision, and marked photophobia.2,3 The clinical signs and symptoms of achromatopsia vary. Typical clinical presentation includes photophobia, pendular nystagmus, poor visual acuity, and color vision deficiency, among others. These symptoms usually start at (Source: Journal of Pediatric ...
Source: Journal of Pediatric Ophthalmology and Strabismus - December 19, 2017 Category: Opthalmology Authors: Isabel Pascual-Camps, MD, PhD Source Type: research
Case of Cone Dystrophy with Normal Fundus Appearance Associated with Biallelic POC1B Variants.
CONCLUSIONS: The cone dystrophy associated with POC1B variants has features similar to achromatopsia, and genetic analyses is useful in discriminating these two diseases.
PMID: 29220607 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - December 10, 2017 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
Ophthalmic features of cone ‐rod dystrophy caused by pathogenic variants in the ALMS1 gene
ConclusionIn summary, we can report that most of our ALMS patients primarily presented with nystagmus and severe photophobia since early childhood interestingly without night blindness in the absence of systemic symptoms. Only genetic testing analysing both nonsyndromic retinal disease (RD) genes and syndromic ciliopathy genes by comprehensive panel sequencing can result in the correct diagnosis, genetically and clinically, with important implication for the physical health of the individual. (Source: Acta Ophthalmologica)
Source: Acta Ophthalmologica - November 30, 2017 Category: Opthalmology Authors: Fadi Nasser, Nicole Weisschuh, Pietro Maffei, Gabriella Milan, Corina Heller, Eberhart Zrenner, Susanne Kohl, Laura Kuehlewein Tags: Original Article Source Type: research
Gene Therapy And Retinal Diseases.
Conclusion Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies.
PMID: 29149824 [PubMed - as supplied by publisher] (Source: Current Gene Therapy)
Source: Current Gene Therapy - November 16, 2017 Category: Genetics & Stem Cells Authors: Campa C, Gallenga CE, Bolletta E, Perri P Tags: Curr Gene Ther Source Type: research
Adaptive optics imaging of inherited retinal diseases.
Abstract
Adaptive optics (AO) ophthalmoscopy allows for non-invasive retinal phenotyping on a microscopic scale, thereby helping to improve our understanding of retinal diseases. An increasing number of natural history studies and ongoing/planned interventional clinical trials exploit AO ophthalmoscopy both for participant selection, stratification and monitoring treatment safety and efficacy. In this review, we briefly discuss the evolution of AO ophthalmoscopy, recent developments and its application to a broad range of inherited retinal diseases, including Stargardt disease, retinitis pigmentosa and ach...
Source: The British Journal of Ophthalmology - November 15, 2017 Category: Opthalmology Authors: Georgiou M, Kalitzeos A, Patterson EJ, Dubra A, Carroll J, Michaelides M Tags: Br J Ophthalmol Source Type: research
Genes, Vol. 8, Pages 280: Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe Inherited Retinal Dystrophies
This study provides the first detailed clinical-genetic assessment of severe IRDs with infantile onset and lays the foundation of a standardized protocol for the selection of patients that are more likely to benefit from gene replacement therapeutic approaches. (Source: Genes)
Source: Genes - October 20, 2017 Category: Genetics & Stem Cells Authors: Valentina Di Iorio Marianthi Karali Raffaella Brunetti-Pierri Mariaelena Filippelli Giuseppina Di Fruscio Mariateresa Pizzo Margherita Mutarelli Vincenzo Nigro Francesco Testa Sandro Banfi Francesca Simonelli Tags: Article Source Type: research
Repeatability and longitudinal assessment of foveal cone structure in cngb3-associated achromatopsia
Conclusion: Foveal cone structure showed little or no change in this group of subjects with CNGB3-associated achromatopsia. Over the time scales investigated (6–26 months), achromatopsia seems to be a structurally stable condition, although longer-term follow-up is needed. These data will be useful in assessing foveal cone structure after therapeutic intervention. (Source: RETINA)
Source: RETINA - September 27, 2017 Category: Opthalmology Tags: Original Study Source Type: research
CNGB3 mutations cause severe rod dysfunction.
CONCLUSION: Although the defect that causes achromatopsia is primarily in the cone photoreceptors, our results reveal an accompanying disruption of rod function that is more severe than has previously been reported. The differential effects on the b-wave relative to the a-wave points to an inner-retinal locus for the disruption of rod function in these patients.
PMID: 28929832 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - September 21, 2017 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
CNGB3 mutation spectrum including copy number variations in 552 achromatopsia patients
Abstract
Achromatopsia is a rare autosomal recessive cone disorder characterized by color vision defects, photophobia, nystagmus, and severely reduced visual acuity. The disease is caused by mutations in genes encoding crucial components of the cone phototransduction cascade (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) or in ATF6, involved in the unfolded protein response. CNGB3 encoding the beta subunit of the cyclic nucleotide‐gated ion channel in cone photoreceptors is the major achromatopsia gene. Here, we present a comprehensive spectrum of CNGB3 mutations and their prevalence in a cohort of 1074 independent families cli...
Source: Human Mutation - August 28, 2017 Category: Genetics & Stem Cells Authors: Anja K. Mayer, Caroline Cauwenbergh, Christine Rother, Britta Baumann, Peggy Reuter, Elfride Baere, Bernd Wissinger, Susanne Kohl, Tags: RESEARCH ARTICLE Source Type: research
Genes, Vol. 8, Pages 208: A Rare Form of Retinal Dystrophy Caused by Hypomorphic Nonsense Mutations in CEP290
Conclusions: Compound heterozygous hypomorphic mutations in CEP290 may lead to a rare form of cone-dominated retinal dystrophy, a novel phenotype belonging to the CEP290-associated spectrum of ciliopathies. These findings provide insight into the effect of CEP290 mutations on the clinical phenotype. (Source: Genes)
Source: Genes - August 22, 2017 Category: Genetics & Stem Cells Authors: Susanne Roosing Frans Cremers Frans Riemslag Marijke Zonneveld-Vrieling Herman Talsma Francoise Klessens-Godfroy Anneke den Hollander L. van den Born Tags: Article Source Type: research
CNGB3 mutation spectrum including copy number variations in 485 achromatopsia patients
This article is protected by copyright. All rights reserved (Source: Human Mutation)
Source: Human Mutation - August 1, 2017 Category: Genetics & Stem Cells Authors: Anja Kathrin Mayer, Caroline Cauwenbergh, Christine Rother, Britta Baumann, Peggy Reuter, , Elfride Baere, Bernd Wissinger, Susanne Kohl Tags: RESEARCH ARTICLE Source Type: research
Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration [Research]
Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB, encode TRs; THRB2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we exami...
Source: FASEB Journal - August 1, 2017 Category: Biology Authors: Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Tags: Research Source Type: research
Colour vision abnormality as the only manifestation of normal pressure hydrocephalus.
DISCUSSION: Achromatopsia may be the first or only NPH symptom. It may be prudent to ask patients with NPH regarding colour vision.
PMID: 28743415 [PubMed - as supplied by publisher] (Source: Archivos de la Sociedad Espanola de Oftalmologia)
Source: Archivos de la Sociedad Espanola de Oftalmologia - July 28, 2017 Category: Opthalmology Tags: Arch Soc Esp Oftalmol Source Type: research
