Impact of gene therapy for canine monogenic diseases on the progress of preclinical studies.
Abstract Rapid progress in knowledge of the organization of the dog genome has facilitated the identification of the mutations responsible for numerous monogenic diseases, which usually present a breed-specific distribution. The majority of these diseases have clinical and molecular counterparts in humans. The affected dogs have thus become valuable models for preclinical studies of gene therapy for problems such as eye diseases, immunodeficiency, lysosomal storage diseases, hemophilia, and muscular dystrophy. Successful gene therapies in dogs have significantly contributed to decisions to run clinical trials for ...
Source: J Appl Genet - March 18, 2020 Category: Genetics & Stem Cells Authors: Switonski M Tags: J Appl Genet Source Type: research

Nystagmus and optical coherence tomography findings in CNGB3-associated achromatopsia
Publication date: Available online 7 March 2020Source: Journal of American Association for Pediatric Ophthalmology and StrabismusAuthor(s): Nashila Hirji, Maria Theodorou, James W. Bainbridge, Nadia Venturi, Michel Michaelides (Source: Journal of American Association for Pediatric Ophthalmology and Strabismus)
Source: Journal of American Association for Pediatric Ophthalmology and Strabismus - March 7, 2020 Category: Opthalmology Source Type: research

Nystagmus and optical coherence tomography findings in CNGB3-associated achromatopsia
To describe the nystagmus characteristics of subjects with molecularly confirmed CNGB3-associated achromatopsia and report the spectral domain optical coherence tomography (SD-OCT) findings in these individuals. (Source: Journal of AAPOS)
Source: Journal of AAPOS - March 6, 2020 Category: Opthalmology Authors: Nashila Hirji, Maria Theodorou, James W. Bainbridge, Nadia Venturi, Michel Michaelides Tags: Major Article Source Type: research

Interocular symmetry of foveal cone topography in congenital achromatopsia.
CONCLUSIONS: These results demonstrate interocular symmetry of the foveal cone mosaic (both density and packing) in ACHM. As cone topography can differ between eyes of a subject, PCD does not completely describe the foveal cone mosaic in ACHM. Nonetheless, these findings are of value in longitudinal monitoring of patients during treatment trials and further suggest that both eyes of a given subject may have similar therapeutic potential and non-study eye can be used as a control. PMID: 32108519 [PubMed - as supplied by publisher] (Source: Current Eye Research)
Source: Current Eye Research - February 28, 2020 Category: Opthalmology Authors: Litts KM, Georgiou M, Langlo CS, Patterson EJ, Mastey RR, Kalitzeos A, Linderman RE, Lam BL, Fishman GA, Pennesi ME, Kay CN, Hauswirth WW, Michaelides M, Carroll J Tags: Curr Eye Res Source Type: research

Macular maldevelopment in ATF6-mediated retinal dysfunction.
Conclusions: The findings, particularly a case with severe macular maldevelopment, may expand on the phenotype previously associated with ATF6-mediated achromatopsia. In addition, the comprehensive electrophysiological assessment suggests that preserved S-cone activity can be detected in this particular molecular sub-type of cone dysfunction. PMID: 31900015 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - January 6, 2020 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research

Nystagmus with pendular low amplitude, high frequency components (PLAHF) in association with retinal disease.
Conclusions: Patients presenting with PLAHF usually had retinal disorders. PMID: 31889465 [PubMed - as supplied by publisher] (Source: Strabismus)
Source: Strabismus - January 2, 2020 Category: Research Tags: Strabismus Source Type: research

Early onset retinal dystrophies: clinical clues to diagnosis for pediatricians
ConclusionsLow vision and nystagmus observed by parents, particularly in the first year of life, may represent a red flag, prompting an appropriate ophthalmological workup for inherited retinal dystrophy. (Source: Italian Journal of Pediatrics)
Source: Italian Journal of Pediatrics - December 21, 2019 Category: Pediatrics Source Type: research

Generation of an induced pluripotent stem cell line (FRIMOi007-A) derived from an incomplete achromatopsia patient carrying a novel homozygous mutation in PDE6C gene
Publication date: Available online 4 September 2019Source: Stem Cell ResearchAuthor(s): Judit Domingo-Prim, Víctor Abad-Morales, Marina Riera, Rafael Navarro, Borja Corcostegui, Esther PomaresAbstractIncomplete achromatopsia (ACHM) is a disorder in which there is function defect of cone photoreceptors in the retina and individuals with such disease retain residual color vision. Here, we have generated an induced pluripotent stem cell (iPSC) line carrying a homozygous mutation in the PDE6C gene, already related with this vision disorder. Skin fibroblasts from a patient with incomplete ACHM were reprogrammed to iPSCs ...
Source: Stem Cell Research - September 5, 2019 Category: Stem Cells Source Type: research

[ASAP] High-Throughput Ca < sup > 2+ < /sup > Flux Assay To Monitor Cyclic Nucleotide-Gated Channel Activity and Characterize Achromatopsia Mutant Channel Function
ACS Chemical NeuroscienceDOI: 10.1021/acschemneuro.9b00231 (Source: ACS Chemical Neuroscience)
Source: ACS Chemical Neuroscience - July 24, 2019 Category: Neuroscience Authors: Marlene A. Jacobson* ‡§, Laura J. Jones†, Dennis J. Colussi‡§, and Jacqueline C. Tanaka† Source Type: research

Akinetopsia with achromatopsia due to focal epilepsy
Publication date: Available online 6 March 2019Source: SeizureAuthor(s): Kengo Maeda, Yoshiko Sugihara, Tomoyuki Shiraishi (Source: Seizure)
Source: Seizure - March 7, 2019 Category: Neurology Source Type: research

Akinetopsia with achromatopsia due to focal epilepsy
Akinetopsia is a rare visual symptom of the central nervous system [1]. There are two types of akinetopsia: invisibility of moving objects, and motionless vision resembling freeze frames in a motion picture (cinematographic vision). Since there are only a few reports of akinetopsia, the corresponding region for motion perception is controversial. We herein describe a patient with ictal akinetopsia with achromatopsia whose symptoms and presentation offer insight in considering the issue. (Source: Seizure: European Journal of Epilepsy)
Source: Seizure: European Journal of Epilepsy - March 6, 2019 Category: Neurology Authors: Kengo Maeda, Yoshiko Sugihara, Tomoyuki Shiraishi Tags: Clinical letter Source Type: research

A nonhuman primate model of inherited retinal disease
Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable r...
Source: Journal of Clinical Investigation - January 23, 2019 Category: Biomedical Science Authors: Ala Moshiri, Rui Chen, Soohyun Kim, R. Alan Harris, Yumei Li, Muthuswamy Raveendran, Sarah Davis, Qingnan Liang, Ori Pomerantz, Jun Wang, Laura Garzel, Ashley Cameron, Glenn Yiu, J. Timothy Stout, Yijun Huang, Christopher J. Murphy, Jeffrey Roberts, Kota Source Type: research

Blinded by the light: a nonhuman primate model of achromatopsia
Achromatopsia is an inherited retinal degeneration characterized by the loss of cone photoreceptor function. In this issue of the JCI, Moshiri et al. characterize a naturally occurring model of the disease in the rhesus macaque caused by homozygous mutations in the phototransduction enzyme PDE6C. Using retinal imaging, and electrophysiologic and biochemical methods, the authors report a clinical phenotype nearly identical to the human condition. These findings represent the first genetic nonhuman primate model of an inherited retinal disease, and provide an ideal testing ground for the development of novel gene replacement...
Source: Journal of Clinical Investigation - January 23, 2019 Category: Biomedical Science Authors: Katherine E. Uyhazi, Jean Bennett Source Type: research

Rod Monochromatism (Achromatopsia).
Authors: Tsang SH, Sharma T Abstract Rod monochromatism (achromatopsia) is a congenital cone photoreceptor disorder, which is rare, affecting about 1 in 30,000 individuals. These patients have normal rod function but no detectable cone function; therefore, everything they see is in shades of gray (total color blindness). Patients usually present in infancy with nystagmus and photophobia. Vision is usually about 20/200 or worse; patients have a hyperopic refractive error. Some patients show paradoxical pupillary response; that is, the pupils dilate in bright light. Fundus examination is normal, though pigmentary mot...
Source: Advances in Experimental Medicine and Biology - December 25, 2018 Category: Research Tags: Adv Exp Med Biol Source Type: research

Accessory heterozygous mutations in cone photoreceptor CNGA3 exacerbate CNG channel–associated retinopathy
Mutations in CNGA3 and CNGB3, the genes encoding the subunits of the tetrameric cone photoreceptor cyclic nucleotide–gated ion channel, cause achromatopsia, a congenital retinal disorder characterized by loss of cone function. However, a small number of patients carrying the CNGB3/c.1208G>A;p.R403Q mutation present with a variable retinal phenotype ranging from complete and incomplete achromatopsia to moderate cone dysfunction or progressive cone dystrophy. By exploring a large patient cohort and published cases, we identified 16 unrelated individuals who were homozygous or (compound-)heterozygous for the CNGB3/c....
Source: Journal of Clinical Investigation - November 13, 2018 Category: Biomedical Science Authors: Markus Burkard, Susanne Kohl, Timm Krätzig, Naoyuki Tanimoto, Christina Brennenstuhl, Anne E. Bausch, Katrin Junger, Peggy Reuter, Vithiyanjali Sothilingam, Susanne C. Beck, Gesine Huber, Xi-Qin Ding, Anja K. Mayer, Britta Baumann, Nicole Weisschuh, Ditt Source Type: research

In Vitro Evaluation of AAV Vectors for Retinal Gene Therapy.
s S Abstract Gene therapy holds promise for treating previously untreatable retinal disorders. The most promising approaches use gene transfer vectors derived from adeno-associated virus (AAV) to supplement a gene function in the affected cell type. One example is gene therapy for achromatopsia which affects daylight vision. In this case, recombinant AAV (rAAV) vectors are being developed to specifically target cone photoreceptors. Development of rAAV vectors could be facilitated by the use of in vitro models. In this chapter we provide a protocol which utilizes mouse 661W cells, an in vitro model of cone photorec...
Source: Mol Biol Cell - October 17, 2018 Category: Molecular Biology Authors: Wagner JE, Schön C, Becirovic E, Biel M, Michalakis S Tags: Methods Mol Biol Source Type: research

Novel causative variants in patients with achromatopsia.
CONCLUSIONS: These novel variants expand the genotypes associated with ACHM and may help in future therapy development for ACHM. PMID: 30289319 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - October 6, 2018 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research

Novel truncating mutation in CACNA1F in a young male patient diagnosed with optic atrophy.
CONCLUSIONS: We show that genetic testing may help to differentiate between optic atrophy, LCA, and CACNA1F-associated retinopathy at a much earlier age, in absence of electrophysiological examination and by widely overlapping phenotypes. PMID: 30260717 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - September 29, 2018 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research

Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia
Human Mutation, EarlyView. (Source: Human Mutation)
Source: Human Mutation - August 22, 2018 Category: Genetics & Stem Cells Authors: NicoleWeisschuh , KatarinaStingl , IsabelleAudo , SaskiaBiskup , B éatriceBocquet , KariBranham , Marie SBurstedt , ElfrideDe Baere , Meindert JDe Vries , IrinaGolovleva , AndrewGreen , JohnHeckenlively , Bart PLeroy , Isabell Source Type: research

The Visual Agnosias and Related Disorders
Conclusions: There has been considerable progress in the understanding of how the extrastriate visual cortex is organized, specifically in relation to functionally specialized visual areas. This permits a better understanding of the individual visual agnosias resulting from damage to these areas. (Source: Journal of Neuro-Ophthalmology)
Source: Journal of Neuro-Ophthalmology - August 18, 2018 Category: Opthalmology Tags: State-of-the-Art Review Source Type: research

Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia
Human Mutation,Volume 0, Issue ja, -Not available-. (Source: Human Mutation)
Source: Human Mutation - August 6, 2018 Category: Genetics & Stem Cells Authors: NicoleWeisschuh , KatarinaStingl , IsabelleAudo , SaskiaBiskup , B éatriceBocquet , KariBranham , Marie SBurstedt , ElfrideDe Baere , Meindert JDe Vries , IrinaGolovleva , AndrewGreen , JohnHeckenlively , Bart PLeroy , Isabell Source Type: research

The UPR Activator ATF6 Responds to Proteotoxic and Lipotoxic Stress by Distinct Mechanisms.
Abstract The unfolded protein response (UPR) is induced by proteotoxic stress of the endoplasmic reticulum (ER). Here we report that ATF6, a major mammalian UPR sensor, is also activated by specific sphingolipids, dihydrosphingosine (DHS) and dihydroceramide (DHC). Single mutations in a previously undefined transmembrane domain motif that we identify in ATF6 incapacitate DHS/DHC activation while still allowing proteotoxic stress activation via the luminal domain. ATF6 thus possesses two activation mechanisms: DHS/DHC activation and proteotoxic stress activation. Reporters constructed to monitor each mechanism...
Source: Developmental Cell - August 6, 2018 Category: Cytology Authors: Tam AB, Roberts LS, Chandra V, Rivera IG, Nomura DK, Forbes DJ, Niwa M Tags: Dev Cell Source Type: research

Six Years and Counting: Restoration of Photopic Retinal Function and Visual Behavior Following Gene Augmentation Therapy in a Sheep Model of CNGA3 Achromatopsia
Human Gene Therapy, Ahead of Print. (Source: Human Gene Therapy)
Source: Human Gene Therapy - July 30, 2018 Category: Genetics & Stem Cells Authors: Ron Ofri Edward Averbukh Raaya Ezra-Elia Maya Ross Hen Honig Alexey Obolensky Alexander Rosov William W Hauswirth Elisha Gootwine Eyal Banin Source Type: research

Foveal hypoplasia in short stature with optic atrophy and Pelger-Huët anomaly syndrome with neuroblastoma-amplified sequence (NBAS) gene mutation
This report describes foveal hypoplasia in a brother and sister with SOPH syndrome, which is associated with defects in the neuroblastoma amplified sequence (NBAS) gene. As NBAS gene may play an important role in retinal homeostasis, patients with SOPH should be monitored carefully for ocular abnormalities. (Source: Journal of American Association for Pediatric Ophthalmology and Strabismus)
Source: Journal of American Association for Pediatric Ophthalmology and Strabismus - July 11, 2018 Category: Opthalmology Source Type: research

ISCEV extended protocol for the dark-adapted red flash ERG
Abstract The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the dark-adapted (DA) red flash ERG. The DA red flash ERG can be incorporated conveniently within the ISCEV standard ERG protocol after a minimum of 20-min DA and recorded after the DA 0.01 ERG to a flash strength of 0.3  phot cd s m−2, eliciting a waveform with two positive peaks in healthy individuals. The first po...
Source: Documenta Ophthalmologica - June 22, 2018 Category: Opthalmology Source Type: research

Gene therapy and genome surgery in the retina
Precision medicine seeks to treat disease with molecular specificity. Advances in genome sequence analysis, gene delivery, and genome surgery have allowed clinician-scientists to treat genetic conditions at the level of their pathology. As a result, progress in treating retinal disease using genetic tools has advanced tremendously over the past several decades. Breakthroughs in gene delivery vectors, both viral and nonviral, have allowed the delivery of genetic payloads in preclinical models of retinal disorders and have paved the way for numerous successful clinical trials. Moreover, the adaptation of CRISPR-Cas systems f...
Source: Journal of Clinical Investigation - June 2, 2018 Category: Biomedical Science Authors: James E. DiCarlo, Vinit B. Mahajan, Stephen H. Tsang Source Type: research

ISCEV extended protocol for the dark-adapted red flash ERG
Abstract The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum procedure, but encourages more extensive testing. This ISCEV extended protocol describes an extension to the ERG standard, namely the dark-adapted (DA) red flash ERG. The DA red flash ERG can be incorporated conveniently within the ISCEV standard ERG protocol after a minimum of 20-min DA and recorded after the DA 0.01 ERG to a flash strength of 0.3  phot cd s m−2, eliciting a waveform with two positive peaks in healthy individuals. The first po...
Source: Documenta Ophthalmologica - June 1, 2018 Category: Opthalmology Source Type: research

Preimplantation genetic diagnosis as a strategy to prevent having a child born with an heritable eye disease.
CONCLUSIONS: Our findings underscore the importance an ophthalmologist plays in informing patients regarding the options now available for using prenatal and preimplantation genetic diagnosis to avoid having a child with a potentially devastating genetic form of eye disease or ocular cancer. This strategy is highly relevant, particularly given the limited options currently available for treating these conditions. PMID: 29781739 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - May 22, 2018 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research

Foveal hypoplasia in a patient with achromatopsia.
Authors: Aydın R, Özbek M, Karaman Erdur S, Şentürk F PMID: 29773314 [PubMed - as supplied by publisher] (Source: Journal Francais d Ophtalmologie)
Source: Journal Francais d Ophtalmologie - May 20, 2018 Category: Opthalmology Tags: J Fr Ophtalmol Source Type: research

Electronegative electroretinogram in achromatopsia
Conclusion: Novel electroretinography findings in a patient with genetically confirmed achromatopsia are reported. The electronegative configuration in this clinical setting is of unclear etiology; however, it may suggest some component of inner retinal dysfunction. (Source: Retinal Cases and Brief Reports)
Source: Retinal Cases and Brief Reports - March 19, 2018 Category: Opthalmology Tags: Case Report 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 - March 16, 2018 Category: Opthalmology Authors: Isabel Pascual-Camps, MD, PhD Source Type: research

Cerebral achromatopsia secondary to ischemic stroke
Chenguang Zhou, Yuanhong He, Xiangying LiNeurology India 2018 66(2):573-575 (Source: Neurology India)
Source: Neurology India - March 15, 2018 Category: Neurology Authors: Chenguang Zhou Yuanhong He Xiangying Li Source Type: research

An early nonsense mutation facilitates the expression of a short isoform of CNGA3 by alternative translation initiation.
r P Abstract The cyclic nucleotide-gated (CNG) channel - composed of CNGA3 and CNGB3 subunits - mediates the influx of cations in cone photoreceptors after light stimulation and thus is a key element in cone phototransduction. Mutations in CNGA3 and CNGB3 are associated with achromatopsia, a rare autosomal recessive retinal disorder. Here, we demonstrate that the presence of an early nonsense mutation in CNGA3 induces the usage of a downstream alternative translation initiation site giving rise to a short CNGA3 isoform. The expression of this short isoform was verified by Western blot analysis and DAB staining of ...
Source: Experimental Eye Research - February 27, 2018 Category: Opthalmology Authors: Täger J, Kohl S, Birch D, Wheaton DKH, Wissinger B, Reuter P Tags: Exp Eye Res Source Type: research

Achromatopsia: clinical features, molecular genetics, animal models and therapeutic options.
This article aims to provide a comprehensive review of the clinical features of the condition, its genetic basis and the underlying pathogenesis. We also explore the insights derived from animal models, including the implications for gene supplementation approaches. Finally, we discuss current human gene therapy trials. PMID: 29303385 [PubMed - as supplied by publisher] (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - January 6, 2018 Category: Opthalmology Tags: Ophthalmic Genet Source Type: research

Loss of the cone-enriched caspase-7 does not affect secondary cone death in retinitis pigmentosa.
Conclusions: Secondary cone death in retinitis pigmentosa is unlikely to be triggered by ER stress and is likely independent of Casp7 activity. PMID: 29296074 [PubMed - in process] (Source: Molecular Vision)
Source: Molecular Vision - January 5, 2018 Category: Molecular Biology Tags: Mol Vis Source Type: research


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 Germany....
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 achromatops...
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 22, 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

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

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