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The Yale Journal of Biology and Medicine Dec 2017Achromatopsia is a rare congenital cause of vision loss due to isolated cone photoreceptor dysfunction. The most common underlying genetic mutations are autosomal... (Review)
Review
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 , , , , , or . Animal models of , , and 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. This review details the AAV gene therapy treatments of achromatopsia to date. We also present novel data showing rescue of a mouse model using an rAAV.CBA.CNGA3 vector. We conclude by synthesizing the implications of this animal work for ongoing human trials, particularly, the challenge of restoring integrated cone retinofugal pathways in an adult visual system. The evidence to date suggests that gene therapy for achromatopsia will need to be applied early in childhood to be effective.
Topics: Animals; Circadian Rhythm; Clinical Trials as Topic; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Dependovirus; Disease Models, Animal; Dogs; Genetic Therapy; Humans; Mice; Retina
PubMed: 29259520
DOI: No ID Found -
Molecular Diagnosis & Therapy Jan 2022Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the... (Review)
Review
Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is an autosomal recessively inherited retinal disorder that affects the cones of the retina, the type of photoreceptors responsible for high-acuity daylight vision. ACHM is caused by pathogenic variants in one of six cone photoreceptor-expressed genes. These mutations result in a functional loss and a slow progressive degeneration of cone photoreceptors. The loss of cone photoreceptor function manifests at birth or early in childhood and results in decreased visual acuity, lack of color discrimination, abnormal intolerance to light (photophobia), and rapid involuntary eye movement (nystagmus). Up to 90% of patients with ACHM carry mutations in CNGA3 or CNGB3, which are the genes encoding the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel, respectively. No authorized therapy for ACHM exists, but research activities have intensified over the past decade and have led to several preclinical gene therapy studies that have shown functional and morphological improvements in animal models of ACHM. These encouraging preclinical data helped advance multiple gene therapy programs for CNGA3- and CNGB3-linked ACHM into the clinical phase. Here, we provide an overview of the genetic and molecular basis of ACHM, summarize the gene therapy-related research activities, and provide an outlook for their clinical application.
Topics: Animals; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Genetic Therapy; Humans; Mutation; Retinal Cone Photoreceptor Cells
PubMed: 34860352
DOI: 10.1007/s40291-021-00565-z -
Cold Spring Harbor Perspectives in... Aug 2014It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was... (Review)
Review
It has been possible to use viral-mediated gene therapy to transform dichromatic (red-green color-blind) primates to trichromatic. Even though the third cone type was added after the end of developmental critical periods, treated animals acquired red-green color vision. What happened in the treated animals may represent a recapitulation of the evolution of trichromacy, which seems to have evolved with the acquisition of a third cone type without the need for subsequent modification to the circuitry. Some transgenic mice in which a third cone type was added also acquired trichromacy. However, compared with treated primates, red-green color vision in mice is poor, indicating large differences between mice and monkeys in their ability to take advantage of the new input. These results have implications for understanding the limits and opportunities for using gene therapy to treat vision disorders caused by defects in cone function.
Topics: Animals; Color Vision Defects; Genetic Therapy; Mice; Nerve Net; Neuronal Plasticity; Opsins; Saimiri
PubMed: 25147187
DOI: 10.1101/cshperspect.a017418 -
Vision Research May 2019Retinal and cortical signals initiated by a single cone type can be recorded using the spectral compensation (or silent substitution) paradigm. Moreover, responses to...
Retinal and cortical signals initiated by a single cone type can be recorded using the spectral compensation (or silent substitution) paradigm. Moreover, responses to instantaneous excitation increments combined with gradual excitation decreases are dominated by the response to the excitation increment. Similarly, the response to a sudden excitation decrement dominates the overall response when combined with a gradual excitation increase. Here ERGs and VEPs were recorded from 34 volunteers [25.9 ± 10.4 years old (mean ± 1 SD); 25 males, 9 females] to sawtooth flicker (4 Hz) stimuli that elicited L- or M-cone responses using triple silent substitution. The mean luminance (284 cd/m) and the mean chromaticity (x = 0.5686, y = 0.3716; CIE 1931 color space) remained constant and thus the state of adaptation was the same in all conditions. Color discrimination thresholds along protan, deutan, and tritan axes were obtained from all participants. Dichromatic subjects were genetically characterized by molecular analysis of their opsin genes. ERG responses to L-cone stimuli were absent in protanopes whereas ERG responses to M-cone stimuli were strongly reduced in deuteranopes. Dichromats showed generally reduced VEP amplitudes. Responses to cone-specific stimuli obtained with standard electrophysiological methods may give the same classification as that obtained with the Cambridge Colour Test and in some cases with the genetic analysis of the L- and M-opsin genes. Therefore, cone-specific ERGs and VEPs may be reliable methods to detect cone dysfunction. The present data confirm and emphasize the potential use of cone-specific stimulation, combined with standard visual electrodiagnostic protocols.
Topics: Adolescent; Adult; Color Perception Tests; Color Vision; Color Vision Defects; Cone Opsins; Electroretinography; Evoked Potentials, Visual; Female; Humans; Male; Young Adult
PubMed: 30844384
DOI: 10.1016/j.visres.2019.02.011 -
The British Journal of Ophthalmology Jan 2016The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying... (Review)
Review
The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. 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 review the current management of these disorders.
Topics: Color Vision Defects; Genotype; Humans; Phenotype; Retinal Cone Photoreceptor Cells; Retinal Diseases; Syndrome
PubMed: 25770143
DOI: 10.1136/bjophthalmol-2014-306505 -
Journal of Visualized Experiments : JoVE Apr 2017Many techniques have been developed to visualize how an image would appear to an individual with a different visual sensitivity: e.g., because of optical or age...
Many techniques have been developed to visualize how an image would appear to an individual with a different visual sensitivity: e.g., because of optical or age differences, or a color deficiency or disease. This protocol describes a technique for incorporating sensory adaptation into the simulations. The protocol is illustrated with the example of color vision, but is generally applicable to any form of visual adaptation. The protocol uses a simple model of human color vision based on standard and plausible assumptions about the retinal and cortical mechanisms encoding color and how these adjust their sensitivity to both the average color and range of color in the prevailing stimulus. The gains of the mechanisms are adapted so that their mean response under one context is equated for a different context. The simulations help reveal the theoretical limits of adaptation and generate "adapted images" that are optimally matched to a specific environment or observer. They also provide a common metric for exploring the effects of adaptation within different observers or different environments. Characterizing visual perception and performance with these images provides a novel tool for studying the functions and consequences of long-term adaptation in vision or other sensory systems.
Topics: Adaptation, Physiological; Aging; Color Perception; Color Perception Tests; Color Vision; Color Vision Defects; Humans; Retina; Visual Cortex
PubMed: 28518063
DOI: 10.3791/54038 -
Advanced Healthcare Materials Jun 2018Color vision deficiency (color blindness) is an inherited genetic ocular disorder. While no cure for this disorder currently exists, several methods can be used to...
Color vision deficiency (color blindness) is an inherited genetic ocular disorder. While no cure for this disorder currently exists, several methods can be used to increase the color perception of those affected. One such method is the use of color filtering glasses which are based on Bragg filters. While these glasses are effective, they are high cost, bulky, and incompatible with other vision correction eyeglasses. In this work, a rhodamine derivative is incorporated in commercial contact lenses to filter out the specific wavelength bands (≈545-575 nm) to correct color vision blindness. The biocompatibility assessment of the dyed contact lenses in human corneal fibroblasts and human corneal epithelial cells shows no toxicity and cell viability remains at 99% after 72 h. This study demonstrates the potential of the dyed contact lenses in wavelength filtering and color vision deficiency management.
Topics: Color Vision Defects; Contact Lenses, Hydrophilic; Cornea; Epithelial Cells; Female; Humans; Male; Materials Testing; Rhodamines
PubMed: 29696828
DOI: 10.1002/adhm.201800152 -
Indian Journal of Ophthalmology May 2021Color vision deficiency (CVD) is a condition that results in individuals being unable to distinguish differences between certain colors. Occupational color vision... (Review)
Review
Color vision deficiency (CVD) is a condition that results in individuals being unable to distinguish differences between certain colors. Occupational color vision standards were introduced in aviation in 1919 by The Aeronautical Commission of the International Civil Air Navigation Authority. Concern has been expressed during the last few years that the current color vision standards in aviation may be too stringent and, at the same time, also variable across the world. The tests employed do not always reflect the tasks pilots encounter in today's aviation environment. This ambiguity leads to the possible exclusion of deserving applicants for selection as aircrew. The compatibility of CVD with aircraft crew is assessed by medical personnel using clinical diagnosis tests on the ground level. These clinical tests were developed specifically to detect the presence, nature, and severity of CVD. No clinical tests yet provide a measure of operational performance in operating an aircraft. Arbitrary pass marks have been assigned to clinical tests such that a failing candidate will either be subject to operational restrictions or excluded completely. The prescribed clinical tests and associated pass marks vary considerably between regulators. While an individual may be subject to no restrictions in one jurisdiction, they may be excluded in another. This article highlights newer diagnostic techniques adopted by different countries for assessing color vision to see for the scope of evidence-based guidelines for minimum color vision requirements for flight crew as well as for civil aviation in India.
Topics: Aviation; Color Perception Tests; Color Vision; Color Vision Defects; Humans; India
PubMed: 33913828
DOI: 10.4103/ijo.IJO_2252_20 -
Scientific Reports Feb 2022Color blindness, or color vision deficiency (CVD), is an ocular disease that suppresses the recognition of different colors. Recently, tinted glasses and lenses have...
Color blindness, or color vision deficiency (CVD), is an ocular disease that suppresses the recognition of different colors. Recently, tinted glasses and lenses have been studied as hopeful devices for color blindness correction. In this study, 2D biocompatible and flexible plasmonic contact lenses were fabricated using polydimethylsiloxane (PDMS) and a low-cost, and simple design based on the soft nano-lithography method and investigated for correction of red-green (deuteranomaly) color blindness. In addition, the stability test of the fabricated plasmonic contact lenses was investigated into the phosphate buffered saline (PBS) solution and the proposed lens offers an excellent stability into the PBS solution. The plasmonic contact lens proposed herein is based on the plasmonic surface lattice resonance (SLR) phenomenon and offers a good color filter for color blindness correction. The biocompatibility, low cost, stability, and simple fabrication of these contact lenses can offer new insights for applications of color blindness correction.
Topics: Biocompatible Materials; Buffers; Color; Color Perception; Color Vision Defects; Contact Lenses; Dimethylpolysiloxanes; Humans; Phosphates; Pliability; Saline Solution; Vision, Ocular
PubMed: 35132172
DOI: 10.1038/s41598-022-06089-8 -
BMC Psychiatry Sep 2022Patients with schizophrenia (SCZ) exhibit poorer color discrimination than normal individuals. Although retinal abnormalities, as well as cortical and subcortical...
BACKGROUND
Patients with schizophrenia (SCZ) exhibit poorer color discrimination than normal individuals. Although retinal abnormalities, as well as cortical and subcortical alterations, found in patients with SCZ have been suggested to cause this poor color discrimination, the impact of cognitive impairment remains to be determined. Dopamine (DA) and glutamate (Glu), known to be disrupted in SCZ, are also suggested to play a role in color discrimination. Our objective was to investigate the contribution of cognitive impairment to color discrimination deficits in SCZ and to examine if these deficits are correlated to SCZ symptoms.
METHODS
This study includes 127 patients with SCZ between July and September 2021. The participants completed several questionnaires, specifically the Positive and Negative Syndrome Scale (PANSS), the Montreal Cognitive Assessment (MoCA) test, and the Farnsworth D-15 test, to assess the extent of SCZ symptoms, cognition, and color discrimination respectively.
RESULTS
Higher cognition (Beta = - 0.279) was significantly associated with a lower total error score (TES). Moreover, a higher positive PANSS score (Beta = 0.217) was significantly associated with a higher TES. A multinomial regression analysis taking the type of color blindness as the dependent variable showed that female sex (ORa = 5.46) was significantly associated with a certain type of color blindness.
CONCLUSION
Color discrimination deficits in patients with SCZ may be due to the effect of cognitive impairment and/or SCZ itself.
Topics: Cognition; Cognitive Dysfunction; Color Vision Defects; Dopamine; Female; Humans; Schizophrenia
PubMed: 36096757
DOI: 10.1186/s12888-022-04245-y