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Genes Jun 2023Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision....
Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (, , , , ) and of the unfolded protein response () have been related to ACHM cases, while and alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the and genes. Patients' genotype and phenotype were retrospectively evaluated. The majority of variants were missense, and the most prevalent variant was c.1148delC (p.Thr383Ilefs*13), resulting in a frameshift and premature stop codon, which is compatible with previous publications in the literature. A novel variant c.1893T>A (p.Tyr631*) in the gene is reported for the first time in this study. A great variability in morphologic findings was observed in our patients, although no consistent correlation with age and disease stage in OCT foveal morphology was found. The better understanding of the genetic variants landscape in the Brazilian population will help in the diagnosis of this disease.
Topics: Humans; Color Vision Defects; Mutation; Brazil; Retrospective Studies; Cyclic Nucleotide-Gated Cation Channels
PubMed: 37372476
DOI: 10.3390/genes14061296 -
Vision Research Jan 2021The object- and light-colour palettes prove to be different for both trichromats and dichromats. This explains why there is no consensus on what colours dichromats see,...
The object- and light-colour palettes prove to be different for both trichromats and dichromats. This explains why there is no consensus on what colours dichromats see, since, until now, studies of dichromatic vision have mainly focused on the light-colour palette. By contrast, this study concentrates on the dichromatic object-colour palette, assuming that it is as much determined by optimal reflectances as the trichromatic palette. In this case, the dichromatic object-colour palette is simply part of the trichromatic object-colour palette. This is a consequence of the fact that the dichromatic optimal reflectances bring about identical perceptions in both dichromats and trichromats. Since the optimal reflectances cannot be physically implemented, a set of Munsell chips was selected that was close enough to the dichromatic optimal reflectances. By examining these chips, trichromats can get an idea of what the dichromatic object-colour palette looks like. These chips clearly contain red, green and blue component hues. As to green, it was tinged with such a considerable amount of white that it was hard to judge its presence even for trichromatic observers. By hue scaling, the amount of component hues (Y, B, R, G, W and Bk) that trichromats see in these chips was evaluated. Although the amount of green was found to be low, its presence for some chips was statistically significant. Thus, dichromats should see all six component hues. Also, the opponency of black and white was confirmed, which contradicts the generally accepted view that grey is a mixture of black and white.
Topics: Color; Color Perception; Color Perception Tests; Color Vision; Color Vision Defects; Humans
PubMed: 33221649
DOI: 10.1016/j.visres.2020.08.011 -
Brain : a Journal of Neurology Nov 2022Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms' reach. Achromatopsia is a severe monogenic heritable...
Recent advances in regenerative therapy have placed the treatment of previously incurable eye diseases within arms' reach. Achromatopsia is a severe monogenic heritable retinal disease that disrupts cone function from birth, leaving patients with complete colour blindness, low acuity, photosensitivity and nystagmus. While successful gene-replacement therapy in non-primate models of achromatopsia has raised widespread hopes for clinical treatment, it was yet to be determined if and how these therapies can induce new cone function in the human brain. Using a novel multimodal approach, we demonstrate for the first time that gene therapy can successfully activate dormant cone-mediated pathways in children with achromatopsia (CNGA3- and CNGB3-associated, 10-15 years). To test this, we combined functional MRI population receptive field mapping and psychophysics with stimuli that selectively measure cone photoreceptor signalling. We measured cortical and visual cone function before and after gene therapy in four paediatric patients, evaluating treatment-related change against benchmark data from untreated patients (n = 9) and normal-sighted participants (n = 28). After treatment, two of the four children displayed strong evidence for novel cone-mediated signals in visual cortex, with a retinotopic pattern that was not present in untreated achromatopsia and which is highly unlikely to emerge by chance. Importantly, this change was paired with a significant improvement in psychophysical measures of cone-mediated visual function. These improvements were specific to the treated eye, and provide strong evidence for successful read-out and use of new cone-mediated information. These data show for the first time that gene replacement therapy in achromatopsia within the plastic period of development can awaken dormant cone-signalling pathways after years of deprivation. This reveals unprecedented neural plasticity in the developing human nervous system and offers great promise for emerging regenerative therapies.
Topics: Humans; Child; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Electroretinography; Retinal Cone Photoreceptor Cells; Genetic Therapy
PubMed: 35998912
DOI: 10.1093/brain/awac226 -
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 -
Vision Research Jun 2022In Moscow in the 1950's, the physicist M. M. Bongard developed the use of silent substitution to establish the number of dimensions of human or animal colour vision and...
In Moscow in the 1950's, the physicist M. M. Bongard developed the use of silent substitution to establish the number of dimensions of human or animal colour vision and to derive colour-matching functions either for whole organisms or for individual neuronal channels. In 1956, he and his colleague M. S. Smirnov reported that extra-foveal human vision was tetrachromatic when tested by the silent-substitution method that they called 'replacement colorimetry'. In the steady state, trichromatic matches were possible in extra-foveal regions, but transients were visible when one such match was replaced by another. If, however, a match was made with four primaries, then a silent substitution was possible; and such matches - unlike trichromatic ones - were stable with light level and with changes in the state of chromatic adaptation. Bongard and Smirnov believed that the fourth receptor had the spectral sensitivity of the rods, but of course they were working long before the discovery of intrinsically photosensitive retinal ganglion cells. On the fiftieth anniversary of Bongard's grievous death, we provide a translation of Bongard and Smirnov's paper on the tetrachromacy of extra-foveal vision. In a commentary, we give the background to their work and provide further details of their apparatus and procedure. We briefly discuss related research and the reception in the West of Bongard and Smirnov's claims. We suggest that an analogy can be made between the tetrachromacy of the parafovea and the 'weak tetrachromacy' of heterozygotes for anomalous colour vision, whose trichromatic matches are not stable with chromatic adaptation.
Topics: Animals; Color Perception; Color Vision; Color Vision Defects; Humans; Male; Retinal Ganglion Cells; Retinal Rod Photoreceptor Cells
PubMed: 34625301
DOI: 10.1016/j.visres.2021.08.007 -
Consciousness and Cognition Mar 2015Unlike those with type 1 blindsight, people who have type 2 blindsight have some sort of consciousness of the stimuli in their blind field. What is the nature of that... (Review)
Review
Unlike those with type 1 blindsight, people who have type 2 blindsight have some sort of consciousness of the stimuli in their blind field. What is the nature of that consciousness? Is it visual experience? I address these questions by considering whether we can establish the existence of any structural-necessary-features of visual experience. I argue that it is very difficult to establish the existence of any such features. In particular, I investigate whether it is possible to visually, or more generally perceptually, experience form or movement at a distance from our body, without experiencing colour. The traditional answer, advocated by Aristotle, and some other philosophers, up to and including the present day, is that it is not and hence colour is a structural feature of visual experience. I argue that there is no good reason to think that this is impossible, and provide evidence from four cases-sensory substitution, achomatopsia, phantom contours and amodal completion-in favour of the idea that it is possible. If it is possible then one important reason for rejecting the idea that people with type 2 blindsight do not have visual experiences is undermined. I suggest further experiments that could be done to help settle the matter.
Topics: Blindness; Color Perception; Consciousness; Humans; Motion Perception; Psychological Theory
PubMed: 25481513
DOI: 10.1016/j.concog.2014.10.011 -
Clinical & Experimental Optometry Nov 2020Diagnosing colour vision deficiency is vital, owing to its impact on the choice of career and activities of daily living. Conventional screening methods require frequent...
BACKGROUND
Diagnosing colour vision deficiency is vital, owing to its impact on the choice of career and activities of daily living. Conventional screening methods require frequent replacement due to soiling of the materials, and hence are expensive and not feasible for large-scale community screening. This study aims to construct and validate a new screening tool, Dalton's pseudo-isochromatic plates (PIP), addressing the disadvantages of the conventional methods.
METHODS
The two phases of the study included the construction and validation of the Dalton's PIP. Construction involved utilising specific wavelengths based on spectral tuning, selection of numerals as targets for the chart and identification of a material with durability and resistance to wear and tear. Validation of the chart was done against the 38-plate edition of Ishihara's PIP by two masked examiners for 1,019 school children aged between 11-17 years (mean ± SD: 14 ± 2 years) as part of a school eye-health program.
RESULTS
The sensitivity and the specificity of the Dalton's PIP was found to be 94.12 per cent (95% CI 71.31-99.85) and 99.60 per cent (95% CI 98.98-99.89) respectively and the positive and negative predictive values were 80 per cent and 99.90 per cent respectively. Dalton's PIP when used with a failure criterion of less than three plates correct in two screening sets had the maximum sensitivity and specificity and the area under the curve was 0.96 (95% CI 0.90-0.99, p < 0.05).
CONCLUSION
The newly constructed Dalton's PIP is found to be a valid screening tool to detect congenital colour vision deficiency and is comparable to the Ishihara PIP. This screening tool with its shorter screening time, cost and longer durability would effectively serve in large-scale vision screening programs.
Topics: Activities of Daily Living; Adolescent; Child; Color Perception Tests; Color Vision Defects; Humans; Schools; Sensitivity and Specificity; Vision Screening
PubMed: 31845416
DOI: 10.1111/cxo.13034 -
The American Journal of Medicine May 2023
Topics: Humans; Color Vision Defects; Biomedical Research
PubMed: 36754131
DOI: 10.1016/j.amjmed.2023.01.019 -
International Journal of Ophthalmology 2017Leber's congenital amaurosis (LCA) and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and... (Review)
Review
Leber's congenital amaurosis (LCA) and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE, PubMed and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium (RPE) derived retinoid isomerohydrolase (RPE65) to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine, porcine and rodent LCA2 models. The recombinant AAV2.hRPE65v2 adeno-associated vector contained the RPE65 cDNA and was replication deficient. Its injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively, could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful, it will lead the way to additional gene therapy attempts to cure monogenic, inherited retinopathies.
PubMed: 28393043
DOI: 10.18240/ijo.2017.03.24 -
Advances in Experimental Medicine and... 2019Activating transcription factor 6 (ATF6) is a key regulator of the unfolded protein response (UPR). In response to endoplasmic reticulum (ER) stress, ATF6 is transported...
Activating transcription factor 6 (ATF6) is a key regulator of the unfolded protein response (UPR). In response to endoplasmic reticulum (ER) stress, ATF6 is transported from the ER to the Golgi apparatus where it is cleaved by intramembrane proteolysis, releasing its cytosolic fragment. The cleaved ATF6 fragment, which is a basic leucine zipper (bZip) transcription factor, translocates to the nucleus and upregulates the expression of ER protein-folding chaperones and enzymes. Mutations in ATF6 cause heritable forms of cone photoreceptor dysfunction diseases. These mutations include missense, nonsense, splice site, and deletion or duplication changes found across the entire ATF6. To date, there are 11 ATF6 mutations reported, and we classified them into three classes based on their functional defects that interrupt distinct steps in the ATF6 signaling pathway.
Topics: Activating Transcription Factor 6; Endoplasmic Reticulum Stress; Golgi Apparatus; Humans; Mutation; Protein Folding; Retinal Cone Photoreceptor Cells; Signal Transduction
PubMed: 31884629
DOI: 10.1007/978-3-030-27378-1_50