Spatially Resolved Spectral Sensitivities as a Potential Read-out Parameter in Clinical Gene Therapeutic Trials
Conclusion: In the present study, residual vision was cone mediated both under photopic and scotopic conditions in young patients with EOSRD associated withRPE65 mutations, but S cone function was severely reduced early on. In rod monochromats, vision was rod mediated both under conditions of dark and light adaptation. These observations are important for ongoing and future clinical trials employing gene therapeutic strategies in both rod-cone dystrophies and achromatopsia.Ophthalmic Res (Source: Ophthalmic Research)
Source: Ophthalmic Research - July 11, 2017 Category: Opthalmology Source Type: research
Endoplasmic reticulum (ER) Ca2+-channel activity contributes to ER stress and cone death in cyclic nucleotide-gated channel deficiency [Cell Biology]
We examined whether preservation of luminal Ca2+ stores through pharmacological and genetic suppression of ER Ca2+ efflux protects cones by attenuating ER stress. We demonstrated that the inhibition of ER Ca2+-efflux channels reduced all three arms of ER-stress signaling while improving opsin trafficking to cone outer segments and decreasing cone death by 20–35%. Cone-specific gene deletion of the inositol-1,4,5-trisphosphate receptor type I (IP3R1) also significantly increased cone density in the CNG-channel-deficient mice, suggesting that IP3R1 signaling contributes to Ca2+ homeostasis and cone survival. Consistent wit...
Source: Journal of Biological Chemistry - July 7, 2017 Category: Chemistry Authors: Michael R. Butler, Hongwei Ma, Fan Yang, Joshua Belcher, Yun–Zheng Le, Katsuhiko Mikoshiba, Martin Biel, Stylianos Michalakis, Anthony Iuso, David Križaȷ, Xi–Qin Ding Tags: Molecular Bases of Disease Source Type: research
The use of contact lenses in low vision rehabilitation: optical and therapeutic applications
Ocular pathology that manifests at an early age has the potential to alter the vision‐dependent emmetropisation mechanism, which co‐ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early‐onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to...
Source: Clinical and Experimental Optometry - June 30, 2017 Category: Opthalmology Authors: Stephen J Vincent Tags: Review Source Type: research
The value of cognitive neuropsychology: The case of vision research.
Abstract
Cognitive neuropsychological evidence is widely viewed as inherently flawed or weak, despite well-reasoned arguments to the contrary by many theorists. Rather than attempting yet another defence of cognitive neuropsychology on logical grounds, we point out through examples that in practice, cognitive neuropsychological evidence is widely accepted as valid and important, and has had a major impact on cognitive theory and research. Objections offered in the abstract rarely arise in the context of actual studies. We develop these points through examples from the domain of vision, discussing cerebral ...
Source: Cognitive Neuropsychology - June 26, 2017 Category: Psychiatry & Psychology Authors: McCloskey M, Chaisilprungraung T Tags: Cogn Neuropsychol Source Type: research
Historical Perspectives on Ancient Greek Derived “a” Prefixed Nomenclature for Acquired Neurocognitive Impairment
AbstractDistinct forms of acquired neurocognitive impairment are often described by “a” prefixed terms that derive from ancient Greek (and in one case Latin). Two modern English language neurological and neuropsychological reference books were searched to identify 17 such terms in contemporary usage: amnesia, akinesia, ataxia, aphasia, agraphia, anosmia, apraxia, athetosis, age usia, achromatopsia, agnosia, alexia, amusia, anomia, anarthria, anosognosia, and acalculia. These were traced to their initial association with acquired neurocognitive impairment in German, English, and French language medical publications from...
Source: Neuropsychology Review - May 8, 2017 Category: Neuroscience Source Type: research
Differences in ocular findings in two siblings: one with complete and other with incomplete achromatopsia
ConclusionOur results showed that cone mosaics were present in the central fovea in the sibling with incomplete ACHM patient. This may explain the better visual acuity and color vision in this sibling. (Source: Documenta Ophthalmologica)
Source: Documenta Ophthalmologica - February 13, 2017 Category: Opthalmology Source Type: research
Color vision abnormality as the sole manifestation of posterior reversible encephalopathy due to post ‐partum HELLP syndrome
We report a post‐partum woman with PRES associated with hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP), in whom color vision abnormality (achromatopsia) was the sole manifestation. Cesarean section was performed at 28 weeks due to headache, epigastralgia, and severe hypertension. HELLP became evident after delivery. On post‐partum day 1, she complained of achromatopsia, stating: “all things look brownish‐gray”. Ophthalmologic examination was normal, but brain magnetic resonance imaging showed occipital lobe lesions, indicative of PRES, and, interestingly, also color vision center (area V4) ...
Source: Journal of Obstetrics and Gynaecology Research - January 20, 2017 Category: OBGYN Authors: Hironori Takahashi, Teppei Matsubara, Shinji Makino, Kenji Horie, Shigeki Matsubara Tags: Case Report Source Type: research
Foveal hypoplasia in short stature with optic atrophy and Pelger-Hu ët 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 AAPOS)
Source: Journal of AAPOS - January 20, 2017 Category: Opthalmology Authors: Jun Woo Park, Soo Jung Lee Tags: Short Reports Source Type: research
Achromatopsia mutations target sequential steps of ATF6 activation [Neuroscience]
Achromatopsia is an autosomal recessive disorder characterized by cone photoreceptor dysfunction. We recently identified activating transcription factor 6 (ATF6) as a genetic cause of achromatopsia. ATF6 is a key regulator of the unfolded protein response. In response to endoplasmic reticulum (ER) stress, ATF6 migrates from the ER to Golgi to... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - January 9, 2017 Category: Science Authors: Wei–Chieh Chiang, Priscilla Chan, Bernd Wissinger, Aȷoy Vincent, Anna Skorczyk–Werner, Macieȷ R. Krawczyłski, Randal J. Kaufman, Stephen H. Tsang, Elise Heon, Susanne Kohl, Jonathan H. Lin Tags: Biological Sciences Source Type: research
Structural modeling of a novel SLC38A8 mutation that causes foveal hypoplasia
ConclusionOur results demonstrate a novel use for OCT‐angiography in confirming FH, and also uncover genotype–phenotype correlations of FH‐linked SLC38A8 mutations.
Here, we report identification by whole‐exome sequencing of a novel disease‐causing mutation to the gene SLC38A8, which encodes a sodium‐coupled neutral amino acid transporter protein and is linked to foveal hypoplasia (FH) of the retina. Through our novel use of OCT‐angiography in the diagnosis of FH, we were able to demonstrate improved diagnostic precision. Structural modeling approaches revealed that this mutation occurs on an extracellular l...
Source: Molecular Genetics & Genomic Medicine - December 31, 2016 Category: Genetics & Stem Cells Authors: Marcus A. Toral, Gabriel Velez, Katherine Boudreault, Kellie A. Schaefer, Yu Xu, Norman Saffra, Alexander G. Bassuk, Stephen H. Tsang, Vinit B. Mahajan Tags: Original Article Source Type: research
[Do We Still Need Electrophysiology in Ophthalmology?]
Authors: Tegetmeyer H
Abstract
Electrophysiological methods in clinical ophthalmology include the full-field electroretinogram (ERG) for assessment of outer and middle retinal layers, pattern ERG (PERG) for assessment of ganglion cell function, the electrooculogram (EOG) for assessment of retinal pigment epithelium function, as well as visual evoked potentials (VEP) for assessment of the visual pathway, including the optic nerve and visual cortex. Multifocal recording techniques for ERG and VEP are used for tests within selected areas of the visual field. Technical progress in ocular imaging, especially op...
Source: Klinische Monatsblatter fur Augenheilkunde - December 17, 2016 Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration [Research]
We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30–40% in a Rpe65–/– mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression lev...
Source: FASEB Journal - November 29, 2016 Category: Biology Authors: Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Tags: Research Source Type: research
Gene Therapy for Achromatopsia
ConclusionDuring the last years, huge progress has been made towards bringing a curative treatment for ACHM into clinics. First clinical trials are ongoing or will be launched soon and are expected to contribute important data on the safety and efficacy of ACHM gene supplementation therapy. (Source: The Journal of Gene Medicine)
Source: The Journal of Gene Medicine - October 31, 2016 Category: Genetics & Stem Cells Authors: Stylianos Michalakis, Christian Sch ön, Elvir Becirovic, Martin Biel Tags: REVIEW ARTICLE Source Type: research
Combination of global electroretinogram and sd ‐oct in the etiology of infantile nystagmus
ConclusionsERG is useful in the etiologic diagnosis and prognosis of infantile nystagmus. Its combination with SD‐OCT allows better characterization of the etiology of nystagmus especially in diseases involving the macula which may guide molecular study, help performing genetic counseling, and facilitate future gene therapy. (Source: Acta Ophthalmologica)
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: M. Bouladi, R. Bouraoui, R. Limaiem, N. Chaker, F. Mghaieth, L. El Matri Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Gene and cell ‐based therapies for inherited retinal disorders: An update
Retinal degenerations present a unique challenge as disease progression is irreversible and the retina has little regenerative potential. No current treatments for inherited retinal disease have the ability to reverse blindness, and current dietary supplement recommendations only delay disease progression with varied results. However, the retina is anatomically accessible and capable of being monitored at high resolution in vivo. This, in addition to the immune‐privileged status of the eye, has put ocular disease at the forefront of advances in gene‐ and cell‐based therapies. This review provides an update on gene th...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 31, 2016 Category: Genetics & Stem Cells Authors: Jesse D. Sengillo, Sally Justus, Yi ‐Ting Tsai, Thiago Cabral, Stephen H. Tsang Tags: Research Article Source Type: research
