cGMP/PKG Signaling and Photoreceptor Degeneration [Membrane Biology]
Photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in phototransduction. Mutations in the cone CNG channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. We have shown endoplasmic reticulum (ER) stress-associated apoptotic cone death and increased phosphorylation of the ER Ca2+ channel inositol 1,4,5-trisphosphate receptor 1 (IP3R1) in CNG channel-deficient mice. We also presented a remarkable elevation of cGMP and an increased activity of the cGMP-dependent protein kinase (protein kinase G, PKG) in CNG channel deficiency. This work investigated whether cGMP/PKG signa...
Source: Journal of Biological Chemistry - August 21, 2015 Category: Chemistry Authors: Ma, H., Butler, M. R., Thapa, A., Belcher, J., Yang, F., Baehr, W., Biel, M., Michalakis, S., Ding, X.-Q. Tags: Cell Biology Source Type: research
Imaging of Retrochiasmal and Higher Cortical Visual Disorders
Retrochiasmal visual pathways include optic tracts, lateral geniculate nuclei, optic radiations, and striate cortex (V1). Homonymous hemianopsia and field defect variants with relatively normal visual acuity suggest that the lesions involve retrochiasmal pathways. From V1, visual input is projected to higher visual association areas that are responsible for perception of objects, faces, colors, and orientation. Visual association areas are classified into ventral and dorsal pathways. Damage to the ventral stream results in visual object agnosia, prosopagnosia, and achromatopsia. Balint syndrome, visual inattention, and pur...
Source: Neuroimaging Clinics - July 22, 2015 Category: Radiology Authors: Bundhit Tantiwongkosi, Noriko Salamon Source Type: research
Imaging of Retrochiasmal and Higher Cortical Visual Disorders
Publication date: August 2015 Source:Neuroimaging Clinics of North America, Volume 25, Issue 3 Author(s): Bundhit Tantiwongkosi, Noriko SalamonTeaser Retrochiasmal visual pathways include optic tracts, lateral geniculate nuclei, optic radiations, and striate cortex (V1). Homonymous hemianopsia and field defect variants with relatively normal visual acuity suggest that the lesions involve retrochiasmal pathways. From V1, visual input is projected to higher visual association areas that are responsible for perception of objects, faces, colors, and orientation. Visual association areas are classified into ventral and ...
Source: Neuroimaging Clinics of North America - July 22, 2015 Category: Radiology Source Type: research
Achromatopsia: a review
Purpose of review: The purposes of this article are to examine the literature published on achromatopsia and provide a comprehensive review of the clinical disease, genetic characteristics, and potential for therapy. Specifically, this article will describe recent advances in gene therapy in animal models, clinical features in human, and barriers to human translation.
Recent findings: Building on prior success with adeno-associated virus (AAV) therapy in mice models for achromatopsia with mutations in the CNGB3, CNGA3, or GNAT2 genes, multiple cone-specific promoters have recently been developed and shown success in mice a...
Source: Current Opinion in Ophthalmology - July 1, 2015 Category: Opthalmology Tags: OCULAR GENETICS: Edited by Alex V. Levin Source Type: research
Mutation of ATF6 causes autosomal recessive achromatopsia
Abstract
Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1–q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Gl...
Source: Human Genetics - June 10, 2015 Category: Genetics & Stem Cells Source Type: research
Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/- mice, an all-cone model of CNGA3 achromatopsia
The CNGA3–/–/Nrl–/– mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function–structure could be rescued in CNGA3–/–/Nrl–/– mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. ...
Source: Human Molecular Genetics - June 8, 2015 Category: Genetics & Stem Cells Authors: Du, W., Tao, Y., Deng, W.-T., Zhu, P., Li, J., Dai, X., Zhang, Y., Shi, W., Liu, X., Chiodo, V. A., Ding, X.-Q., Zhao, C., Michalakis, S., Biel, M., Zhang, Z., Qu, J., Hauswirth, W. W., Pang, J.-j. Tags: ARTICLES Source Type: research
Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia
Nature Genetics 47, 757 (2015).
doi:10.1038/ng.3319
Authors: Susanne Kohl, Ditta Zobor, Wei-Chieh Chiang, Nicole Weisschuh, Jennifer Staller, Irene Gonzalez Menendez, Stanley Chang, Susanne C Beck, Marina Garcia Garrido, Vithiyanjali Sothilingam, Mathias W Seeliger, Franco Stanzial, Francesco Benedicenti, Francesca Inzana, Elise Héon, Ajoy Vincent, Jill Beis, Tim M Strom, Günther Rudolph, Susanne Roosing, Anneke I den Hollander, Frans P M Cremers, Irma Lopez, Huanan Ren, Anthony T Moore, Andrew R Webster, Michel Michaelides, Robert K Koenekoop, Eberhart Zrenner, Randal J Kaufman, Stephen H Tsang, B...
Source: Nature Genetics - June 1, 2015 Category: Genetics & Stem Cells Authors: Susanne KohlDitta ZoborWei-Chieh ChiangNicole WeisschuhJennifer StallerIrene Gonzalez MenendezStanley ChangSusanne C BeckMarina Garcia GarridoVithiyanjali SothilingamMathias W SeeligerFranco StanzialFrancesco BenedicentiFrancesca InzanaElise HéonAjoy Vin Tags: Article Source Type: research
Retinal Development in Infants and Young Children with Achromatopsia
Normally, postnatal development of the human retina involves centrifugal displacement of the inner retinal layers (IRLs) from the fovea, centripetal migration of the cone photoreceptors into the fovea, and elongation of the photoreceptors with age.1,2 It is not clear whether retinal development in infants and young children with achromatopsia (ACHM) occurs in a similar way and whether any retinal changes that occur are progressive in early childhood. (Source: Ophthalmology)
Source: Ophthalmology - May 9, 2015 Category: Opthalmology Authors: Helena Lee, Ravi Purohit, Viral Sheth, Rebecca J. McLean, Susanne Kohl, Bart P. Leroy, Venki Sundaram, Michel Michaelides, Frank A. Proudlock, Irene Gottlob Tags: Reports Source Type: research
Jalili syndrome presenting with situs inversus totalis and keratoconus: the first case in the Indian subcontinent
Jalili syndrome (JS) (MIM#217080) is a rare genetic disorder characterized by the co morbid appearance of cone–rod dystrophy (CORD) and amelogenesis imperfecta (AI). JS is an autosomal recessive inherited disorder caused by different mutations all with a linkage at achromatopsia locus 2q11 on the metal transporter gene, CNNM4. The case report presented describes JS with distinct phenotypic variations such as situs inversus totalis (SIT) along with additional ophthalmic findings like keratoconus and ectopia lentis. (Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics)
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - April 23, 2015 Category: ENT & OMF Authors: Parth Purwar, Sagar Sareen, Kishlay Bhartiya, Sayyed Rayyan Sayed Inayatullah, Mayank Bansal, Vikas Chahal, Sanjay Gupta, Jaya Dixit, Vaibhav Sheel, Priya Rai Source Type: research
Novel CNGA3 mutations in Chinese patients with achromatopsia
Conclusions
CNGA3 mutation is the most frequent cause of ACHM in this cohort of patients. Ten novel mutations were identified in CNGA3. Genetic characterisation of patients with ACHM is important for genetic counselling and future gene therapies. This study reports the comprehensive clinical and genetic features of Chinese patients with ACHM. (Source: British Journal of Ophthalmology)
Source: British Journal of Ophthalmology - March 23, 2015 Category: Opthalmology Authors: Liang, X., Dong, F., Li, H., Li, H., Yang, L., Sui, R. Tags: Public health, Vision, Neurology Original articles - Laboratory science Source Type: research
The cone dysfunction syndromes.
We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly...
Source: The British Journal of Ophthalmology - March 13, 2015 Category: Opthalmology Authors: Aboshiha J, Dubis AM, Carroll J, Hardcastle AJ, Michaelides M Tags: Br J Ophthalmol Source Type: research
Achromatopsia in three sibling Labrador Retrievers in the UK
Abstract
Achromatopsia was identified in three Labrador Retriever littermates. The dogs demonstrated day blindness, negotiating obstacles under low‐light conditions, but apparently blind when outdoors. One of the dogs presented with immature bilateral diffuse posterior cortical cataracts and clinical signs of day blindness became apparent following cataract extraction surgery. Electroretinography demonstrated an absence of a cone photoreceptor response to a bright stimulus and a flicker response of 30 Hz in all three dogs. No fundic lesions have been apparent ophthalmoscopically in any of the dogs as the initial present...
Source: Veterinary Ophthalmology - March 1, 2015 Category: Veterinary Research Authors: Christopher J. Dixon Tags: Case Report Source Type: research
Novel CNGA3 mutations in Chinese patients with achromatopsia.
CONCLUSIONS: CNGA3 mutation is the most frequent cause of ACHM in this cohort of patients. Ten novel mutations were identified in CNGA3. Genetic characterisation of patients with ACHM is important for genetic counselling and future gene therapies. This study reports the comprehensive clinical and genetic features of Chinese patients with ACHM.
PMID: 25637600 [PubMed - as supplied by publisher] (Source: The British Journal of Ophthalmology)
Source: The British Journal of Ophthalmology - January 30, 2015 Category: Opthalmology Authors: Liang X, Dong F, Li H, Li H, Yang L, Sui R Tags: Br J Ophthalmol Source Type: research
Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K)
Ophthalmic Genetics, Ahead of Print. (Source: Ophthalmic Genetics)
Source: Ophthalmic Genetics - January 21, 2015 Category: Opthalmology Tags: article Source Type: research
Genetics and Disease Expression in the Form of Achromatopsia
Achromatopsia (ACHM) is a congenital, autosomal recessive retinal disease that manifests cone dysfunction, reduced visual acuity and color vision, nystagmus, and photoaversion. Five genes are known causes of ACHM. The present study took steps toward performing a trial of gene therapy in ACHM by characterizing the genetics of ACHM in Israel and the Palestinian Territories and analyzing retinal function and structure in CNGA3 ACHM patients from the Israeli–Palestinian population and US patients with other origins. (Source: Ophthalmology)
Source: Ophthalmology - January 20, 2015 Category: Opthalmology Authors: Lina Zelinger, Artur V. Cideciyan, Susanne Kohl, Sharon B. Schwartz, Ada Rosenmann, Dalia Eli, Alexander Sumaroka, Alejandro J. Roman, Xunda Luo, Cassondra Brown, Boris Rosin, Anat Blumenfeld, Bernd Wissinger, Samuel G. Jacobson, Eyal Banin, Dror Sharon Source Type: research
