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Investigative Ophthalmology & Visual... Feb 2021Emmetropization is the process of adjusting ocular growth to the focal plane in order to achieve a clear image. Chromatic light may be involved as a cue to guide this...
PURPOSE
Emmetropization is the process of adjusting ocular growth to the focal plane in order to achieve a clear image. Chromatic light may be involved as a cue to guide this process. Achromats are color blind and lack normal cone function; they are often described as being hyperopic, indicating a failure to emmetropize. We aim to describe the refraction and refractive development in a population of genetically characterized achromats.
METHODS
Refractive error data were collected retrospectively from 28 medical records of CNGB3 c.1148delC homozygous achromats. The distribution of spherical equivalent refractive error (SER) and spherical error was analyzed in adults. The refractive development in children was analyzed by documenting astigmatic refractive error and calculating median SER in 1-year age groups and by analyzing the individual development when possible.
RESULTS
The distribution of SER and spherical error resembled a Gaussian distribution, indicating that emmetropization was disturbed in achromats, but we found indication of some decrease in SER during the first years of childhood. The prevalence of refractive errors was high and broadly distributed. Astigmatic refractive errors were frequent but did not seem to increase with age.
CONCLUSIONS
Refractive development in achromats is more complicated than a complete failure to emmetropize. The spread of refractive errors is larger than previously documented. Results presented here support the theory that chromatic cues and cone photoreceptors may play a role in emmetropization in humans but that it is not essential.
Topics: Accommodation, Ocular; Adolescent; Adult; Aged; Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Female; Follow-Up Studies; Humans; Male; Middle Aged; Refraction, Ocular; Refractive Errors; Retrospective Studies; Time Factors; Young Adult
PubMed: 33560291
DOI: 10.1167/iovs.62.2.10 -
Stem Cell Research & Therapy Nov 2023Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making... (Review)
Review
Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.
Topics: Animals; Humans; Induced Pluripotent Stem Cells; Retina; Retinal Degeneration; Retinitis Pigmentosa; Organoids
PubMed: 38012786
DOI: 10.1186/s13287-023-03564-5 -
Genes Jun 2024Inherited cone disorders (ICDs) are a heterogeneous sub-group of inherited retinal disorders (IRDs), the leading cause of sight loss in children and working-age adults.... (Review)
Review
Inherited cone disorders (ICDs) are a heterogeneous sub-group of inherited retinal disorders (IRDs), the leading cause of sight loss in children and working-age adults. ICDs result from the dysfunction of the cone photoreceptors in the macula and manifest as the loss of colour vision and reduced visual acuity. Currently, 37 genes are associated with varying forms of ICD; however, almost half of all patients receive no molecular diagnosis. This review will discuss the known ICD genes, their molecular function, and the diseases they cause, with a focus on the most common forms of ICDs, including achromatopsia, progressive cone dystrophies (CODs), and cone-rod dystrophies (CORDs). It will discuss the gene-specific therapies that have emerged in recent years in order to treat patients with some of the more common ICDs.
Topics: Humans; Color Vision Defects; Cone-Rod Dystrophies; Retinal Cone Photoreceptor Cells; Cone Dystrophy; Blindness; Animals; Genetic Therapy
PubMed: 38927662
DOI: 10.3390/genes15060727 -
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 -
Journal of Personalized Medicine Jul 2023(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological,...
(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological, functional characteristics, and quality of life in a large sample size of patients with achromatopsia. (2) A total of 94 achromats were included in this retrospective cohort study. Sixty-four were patients of the Department of Ophthalmology, Saarland University Medical Centre in Homburg/Saar, Germany, between 2008 and 2021. Thirty further participants with achromatopsia from the national support group were included using an online questionnaire, which is available under 'Supplementary data'. Statistical analysis was performed using SPSS Version 25; (3) The 94 patients (37 males (39.4%) and 57 females (60.6%)) showed a mean age of 24.23 ± 18.53 years. Visual acuity was stable (SD ± 0.22 logMAR at 1.0 logMAR) over a time of observation from 2008 to 2021. Edge filter glasses were the most used optical aids, while enlarged reading glasses were the most used low vision aids. (4) Conclusions: Our findings give an insight into describing the natural process and the quality of life of achromatopsia. The results demonstrate that achromatopsia is a predominantly stationary disease. The individual prescription of edge filters and low-vision aids is essential following a personalised fitting.
PubMed: 37511719
DOI: 10.3390/jpm13071106 -
Genes Mar 2023Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are...
Achromatopsia is a rare congenital condition with cone photoreceptor dysfunction causing color blindness, reduced vision, nystagmus and photophobia. New treatments are being developed, but the current evidence is still conflicting regarding possible progression over time, and there is no clear genotype-phenotype correlation. This natural history study aimed to further explore the course of disease and potential clinical differences between various genotypes. The retrospective design allowed for the study of a large cohort with a long follow-up. Patients were identified from the Danish national registries. If not already available, genetic analysis was offered to the patient. Clinical data from 1945-2022 were retrieved from medical records and included best-corrected visual acuity (BCVA), color vision, refractive error, nystagmus, visual fields and fundoscopic findings. We identified variants believed to be disease causing in five of the known achromatopsia genes: ; ; ; and ; and novel variants were identified in and . Progressive deterioration of BCVA only attributable to achromatopsia was found in three of 58 patients. Progressive phenotype was seen with variants in and The results indicate that myopia could be more frequently occurring with variants in , and and support the evidence that achromatopsia is a predominantly stationary condition with respect to BCVA. Although a clear genotype-phenotype correlation can still not be concluded, there may be differences in phenotypical characteristics with variants in different genes.
Topics: Humans; Color Vision Defects; Retrospective Studies; Cyclic Nucleotide-Gated Cation Channels; Denmark
PubMed: 36980963
DOI: 10.3390/genes14030690 -
Progress in Retinal and Eye Research Jan 2024The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding,... (Review)
Review
The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.
Topics: Humans; Retinal Degeneration; Diabetic Retinopathy; Unfolded Protein Response; Endoplasmic Reticulum Stress; Retina; Endoplasmic Reticulum; Homeostasis
PubMed: 38092262
DOI: 10.1016/j.preteyeres.2023.101231 -
Investigative Ophthalmology & Visual... Dec 2019To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.
PURPOSE
To perform deep phenotyping of subjects with PDE6C achromatopsia and examine disease natural history.
METHODS
Eight subjects with disease-causing variants in PDE6C were assessed in detail, including clinical phenotype, best-corrected visual acuity, fundus autofluorescence, and optical coherence tomography. Six subjects also had confocal and nonconfocal adaptive optics scanning light ophthalmoscopy, axial length, international standard pattern and full-field electroretinography (ERG), short-wavelength flash (S-cone) ERGs, and color vision testing.
RESULTS
All subjects presented with early-onset nystagmus, decreased best-corrected visual acuity, light sensitivity, and severe color vision loss, and five of them had high myopia. We identified three novel disease-causing variants and provide phenotype data associated with nine variants for the first time. No subjects had foveal hypoplasia or residual ellipsoid zone (EZ) at the foveal center; one had an absent EZ, three had a hyporeflective zone, and four had outer retinal atrophy. The mean width of the central EZ lesion on optical coherence tomography at baseline was 1923 μm. The mean annual increase in EZ lesion size was 48.3 μm. Fundus autofluorescence revealed a central hypoautofluorescence with a surrounding ring of increased signal (n = 5). The mean hypoautofluorescent area at baseline was 3.33 mm2 and increased in size by a mean of 0.13 mm2/year. Nonconfocal adaptive optics scanning light ophthalmoscopy revealed residual foveal cones in only one of two cases. Full-field ERGs were consistent with severe generalized cone system dysfunction but with relative preservation of S-cone sensitivity.
CONCLUSIONS
PDE6C retinopathy is a severe cone dysfunction syndrome often presenting as typical achromatopsia but without foveal hypoplasia. Myopia and slowly progressive maculopathy are common features. There are few (if any) residual foveal cones for intervention in older adults.
Topics: Adolescent; Adult; Child; Color Vision; Color Vision Defects; Cyclic Nucleotide Phosphodiesterases, Type 6; Electroretinography; Eye Proteins; Female; Follow-Up Studies; Forecasting; Humans; Male; Middle Aged; Ophthalmoscopy; Phenotype; Tomography, Optical Coherence; Visual Acuity; Young Adult
PubMed: 31826238
DOI: 10.1167/iovs.19-27761 -
Communications Biology Mar 2022Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often...
Numerous missense mutations in cyclic nucleotide-gated (CNG) channels cause achromatopsia and retinitis pigmentosa, but the underlying pathogenic mechanisms are often unclear. We investigated the structural basis and molecular/cellular effects of R410W, an achromatopsia-associated, presumed loss-of-function mutation in human CNGA3. Cryo-EM structures of the Caenorhabditis elegans TAX-4 CNG channel carrying the analogous mutation, R421W, show that most apo channels are open. R421, located in the gating ring, interacts with the S4 segment in the closed state. R421W disrupts this interaction, destabilizes the closed state, and stabilizes the open state. CNGA3_R410W/CNGB3 and TAX4_R421W channels are spontaneously active without cGMP and induce cell death, suggesting cone degeneration triggered by spontaneous CNG channel activity as a possible cause of achromatopsia. Our study sheds new light on CNG channel allosteric gating, provides an impetus for a reevaluation of reported loss-of-function CNG channel missense disease mutations, and has implications for mutation-specific treatment of retinopathy.
Topics: Color Vision Defects; Cyclic Nucleotide-Gated Cation Channels; Humans; Light Signal Transduction; Mutation, Missense; Retinal Cone Photoreceptor Cells
PubMed: 35233102
DOI: 10.1038/s42003-022-03120-6 -
Indian Journal of Ophthalmology Jun 2022To determine the pattern of refractive error among commercial drivers in north India.
PURPOSE
To determine the pattern of refractive error among commercial drivers in north India.
METHODS
Descriptive study with convenient sampling conducted among commercial drivers of north India.
RESULTS
A total of 213 (75.8%) heavy-vehicle and 68 (24.2%) light-vehicle drivers were screened for eye diseases. Refractive error for distance was reported in 44 (15.7%; 95% CI: 11.6-20.4) drivers. Hyperopia was reported in 23 (8.2%; 95% CI: 5.2-12) drivers, followed by myopia in 15 (5.3%; 95% CI: 3-8.6) drivers and astigmatism in six (2.1%; 95% CI: 0.7-4.5) drivers. Presbyopia was reported in 157 (55.8%) drivers. Dry eye was reported in 70 (24.9%), stereo deficiency in 77 (27.4%), and color vision deficiency in 11 (3.9%) drivers. Three drivers were diagnosed with cataract, and two were referred for retina evaluation.
CONCLUSION
Hyperopia in both eyes was the most common refractive error. Dry eye disease and color vision deficiency were also reported. Most of the drivers were not using spectacles for refractive error correction. Due to their mobile nature, drivers with cataract and retina diseases did not turn up for follow-up.
Topics: Cataract; Color Vision Defects; Humans; Hyperopia; Prevalence; Refractive Errors
PubMed: 35647994
DOI: 10.4103/ijo.IJO_2510_21