Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.
- MeSH
- ABC transportéry genetika MeSH
- fenotyp MeSH
- kadherinové proteiny MeSH
- lidé MeSH
- makulární degenerace * genetika MeSH
- mutace MeSH
- oční proteiny MeSH
- penetrance MeSH
- proteiny nervové tkáně genetika MeSH
- retina MeSH
- rodokmen MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single-cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species-specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale.
Úvod: Torpédo makulopatia je vzácna, vrodená ložisková lézia sietnice. Klinický obraz je typický unilaterálnou, ohraničenou, oválnou, hypopigmentovou léziou v inferotemporálnej časti makuly. Vo väčšine prípadov sa lézia nachádza pozdĺž horizontálneho rafé, má tvar torpéda a nazálny okraj smeruje do foveoly. Diagnóza je stanovená na základe jej charakteristického tvaru, lokalizácie a nálezu na optickej koherentnej tomografii (OCT). Etiológia a patogenéza vzniku torpédo makulopatie je nejasná, ale predpokladá sa, že ide o vrodený defekt retinálneho pigmentového epitelu (RPE). Cieľom publikácie je poukázať na túto diagnózu a odprezentovať nález torpédo makulopatie u dospelej pacientky. Kazuistika: 30-ročná pacientka sa dostavila na rutinné očné vyšetrenie. Vyšetrenie očného pozadia pravého oka odhalilo inferotemporálne od fovey oválnu hypopigmentovú léziu veľkosti 1 priemeru disku, na ktorú nadväzovalo satelitné ložisko v rovnakej osi smerujúcej do foveoly. Na základe OCT, OCT angiografie, fundusautofluorescencie, odberu anamnézy, typického tvaru a lokality lézie bola pacientke diagnostikovaná torpédo makulopatia na pravom oku. Záver: Vo všeobecnosti je torpédo makulopatia asymptomatická, vrodená, benígna lézia sietnice. Väčšinou je náhodne diagnostikovaná pri vyšetrení očného pozadia. Ide o stabilný nález s minimálnym rizikom poškodenia zrakových funkcií, ktorý nevyžaduje žiadnu liečbu. Napriek tomu sa vzhľadom na malé riziko vzniku choroidálnej neovaskulárnej membrány odporúča sledovanie pacientov raz ročne. Na túto diagnózu je nutné myslieť pri náleze unilaterálneho hypopigmentového ložiska inferotemporálne od fovey a v rámci diferenciálnej diagnostiky ho odlíšiť od chorioretinálnej atrofie, jazvy, kolobómu, viteliformnej dystrofie, či iných lézií RPE.
Aim: Torpedo maculopathy is an incidental, congenital retinal lesion. The typical clinical finding is a unilateral, symmetric, oval, hypopigmented lesion in the inferotemporal macula. In most cases, the lesion is along the horizontal raphe, is torpedo-shaped, and the nasal edge is directed into the foveola. The diagnosis is determined on the basis of its characteristic shape, localization and findings on optical coherence tomography (OCT). The etiology and pathogenesis of torpedo maculopathy is unclear, but it is believed to be a congenital defect of the retinal pigment epithelium (RPE). The aim of this publication is highlight this diagnosis and to present an incidental finding of torpedo maculopathy in an adult patient. Case report: A 30-year-old female patient reported for a routine eye examination. Fundus examination of the right eye revealed an oval hypopigmented lesion with a size of 1 disk diameter inferotemporally from the fovea, which was followed by a satellite lesion in the same axis directed into the foveola. Based on OCT, OCT angiography, fundus autofluorescence, and the typical shape and location of the lesion, the patient was diagnosed with torpedo maculopathy in the right eye. Conclusion: In general, torpedo maculopathy is an asymptomatic, congenital, benign retinal lesion, which is mostly diagnosed accidentally during a routine fundus examination. TM is non-progressive retinal finding with a minimal risk of deterioration of visual functions, which does not require any treatment. Nevertheless, due to the rare risk of a choroidal neovascular membrane, it is recommended to examine patients once a year. It is necessary to consider this diagnosis when a unilateral hypopigmented lesion is found inferotemporally from the fovea, and to distinguish it from chorioretinal atrophy, scar, vitelliform dystrophy, or other RPE lesions as part of the differential diagnosis.
- MeSH
- dospělí MeSH
- lidé MeSH
- nemoci retiny * diagnóza terapie MeSH
- optická koherentní tomografie metody MeSH
- retina patologie MeSH
- retinální pigmentový epitel patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Úvod: Alzheimerova nemoc (AN), nejčastější příčina demence, postihuje podle odhadů 3–40 % populace hlavně vyššího věku a její incidence narůstá. Představuje velkou zátěž pro zdravotnický systém. Standardní diagnostická neurokognitivní vyšetření jsou náročná jak časově, tak finančně, proto je snaha o nalezení vhodné screeningové metody rizikových pacientů. Sítnice oka je embryologicky prodloužením mozku a lze předpokládat úzkou souvislost mezi stavem sítnice, detekovaným pomocí optické koherentní tomografie (OCT), a kognitivními funkcemi. Cílem práce bylo provést systematický přehled studií, které se zabývaly vztahem mezi tloušťkou nervových vláken sítnice (RNFL – retinal nerve fibre layer), a kognitivními funkcemi u pacientů Alzheimerovou nemocí. Metody: Z databází PubMed a Google Scholar byly na základě zvolených klíčových slov: Optical coherence tomography, dementia, retinal nerve fibre layer, cognitive function vybrány relevantní studie, které sledovaly změny tloušťky nervových vláken sítnice pomocí OCT a jejich vztah s výskytem Alzheimerovy nemoci. Výsledky: Do analýzy bylo zařazeno 16 studií. Většina prací konzistentně prokázala vztah mezi tloušťkou nervových vláken při OCT a výskytem Alzheimerovy nemoci. V naprosté většině studií bylo pozorováno snížení tloušťky pRNFL (papilární tloušťka nervových vláken) v horních a dolních kvadrantech, zatímco v nasálních a temporálních kvadrantech tento pokles nebyl zaznamenán. Snížení tloušťky pRNFL bylo detekováno i u pacientů s mírným kognitivním deficitem. Závěr: Snížení tloušťky nervových vláken pomocí neinvazivního vyšetření OCT koreluje s výskytem Alzheimerovy nemoci. OCT by ta
: Alzheimer disease (AD) as the most common cause of dementia, is affecting approximately 3-40 % of the elderly population and its incidence grows. It is a great burden for healthcare system. Standard diagnostic neurocognitive examination is time consuming and quite expensive. Therefore there is need for fast and accurate screening test. The retina of the eye is embryologically extension of the brain so it is assumed that there is correlation between status of the retina detected by optical coherence tomography and cognitive function. The aim of this study is to create a systematic review of studies which analysed correlation betwen retinal nerve fiber layer thickness (RNFL) and cognitive functions in patients with Alzheimer disease. Methods: Relevant studies from PubMed and Google scholar were searched using key words: Optical coherence tomography, dementia, retinal nerve fibre layer, cognitive function. Only results of studies where RNFL was measured with OCT scan and their association with Alzheimer disease were then analysed. Results: There were 16 studies eligible for the analysis. Most studies consistently proved association between RNFL thickness at the OCT and the presence of Alzheimer disease. In nearly every available study there is thinning of RNFL in superior and inferior quadrants, while in nasal and temporal quadrants there was no significant thinning present. Conclusion: So far as the results are being reviewed, there is an evidence that patients with Alzheimer disease have their retinal nerve fibre layer thickness decreased. This finding could lead to faster diagnosis of this disease and better therapeutical approach in this group of patients. There is sought for other studies with larger cohort and with modern imaging devices and software.
Primary cilia are cellular surface projections enriched in receptors and signaling molecules, acting as signaling hubs that respond to stimuli. Malfunctions in primary cilia have been linked to human diseases, including retinopathies and ocular defects. Here, we focus on TMEM107, a protein localized to the transition zone of primary cilia. TMEM107 mutations were found in patients with Joubert and Meckel-Gruber syndromes. A mouse model lacking Tmem107 exhibited eye defects such as anophthalmia and microphthalmia, affecting retina differentiation. Tmem107 expression during prenatal mouse development correlated with phenotype occurrence, with enhanced expression in differentiating retina and optic stalk. TMEM107 deficiency in retinal organoids resulted in the loss of primary cilia, down-regulation of retina-specific genes, and cyst formation. Knocking out TMEM107 in human ARPE-19 cells prevented primary cilia formation and impaired response to Smoothened agonist treatment because of ectopic activation of the SHH pathway. Our data suggest TMEM107 plays a crucial role in early vertebrate eye development and ciliogenesis in the differentiating retina.
- MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- myši MeSH
- polycystická choroba ledvin * genetika MeSH
- poruchy ciliární motility * genetika metabolismus MeSH
- retina metabolismus MeSH
- retinopathia pigmentosa * metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.
BACKGROUND AND OBJECTIVES: Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment. METHODS: To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study. RESULTS: We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (κ 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (κ 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria. DISCUSSION: We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies.
BACKGROUND: The authors present a case study which describes the development of bilateral optic neuropathy as a complication of allogeneic hematopoietic stem cell transplantation (HSCT) in a patient who underwent a transplant for B-cell acute lymphoblastic leukemia (B-ALL). The patient, who was in remission with regard to the underlying hematological disease, developed edema of both optic discs and maculas three months after transplantation. The morphological finding regressed after treatment with corticoids and comprehensive systemic anti-infective therapy. However, the loss of function was not entirely restored. CASE REPORT: One year after the healing, the atrophy of the optic discs persisted, with corresponding findings in vessel density (VD), retinal nerve fibre layer (RNFL) and visual field changes. Electrophysiological examination by pattern electroretinogram (PERG) showed an alteration in retinal ganglion cells in the left eye, but with significant damage to nerve fibres on both sides. Visual evoked potential (VEP) verified bilateral non-inflammatory neurogenic lesions. This finding was also confirmed by functional magnetic resonance imaging (fMRI). Examination by structural magnetic resonance imaging (MRI) showed inflammatory changes in the optic nerve sheaths over time and a consequent marked narrowing of them. CONCLUSION: The authors believe that edema of the optic discs and maculas was caused by a combination of several factors. Firstly, MRI showed inflammatory changes in the optic nerve sheaths, which led to a blockade of axoplasmic transport. Another factor that may have played a part in the outcome was endothelial damage to blood vessels with impaired microcirculation supplying the optic nerve fibres, which contributed to the occurrence of macular edema.
OBJECTIVES: The electroretinogram is a clinical test commonly used in the diagnosis of retinal disorders with the peak time and amplitude of the a- and b-waves used as the main indicators of retinal function. However, subtle changes that affect the shape of the electroretinogram waveform may occur in the early stages of disease or in conditions that have a neurodevelopmental or neurodegenerative origin. In such cases, we introduce a statistical approach to mathematically model the shape of the electroretinogram waveform that may aid clinicians and researchers using the electroretinogram or other biological signal recordings to identify morphological features in the waveforms that may not be captured by the time or time-frequency domains of the waveforms. We present a statistical graphics-based analysis of the ascending limb of the b-wave (AL-b) of the electroretinogram in children with and without a diagnosis of autism spectrum disorder (ASD) with a narrative explanation of the statistical approach to illustrate how different features of the waveform based on location and scale derived from raw and registered time series can reveal subtle differences between the groups. RESULTS: Analysis of the raw time trajectories confirmed findings of previous studies with a reduced and delayed b-wave amplitude in ASD. However, when the individual time trajectories were registered then group differences were visible in the mean amplitude at registered time ~ 0.6 suggesting a novel method to differentiate groups using registration of the ERG waveform.
- MeSH
- časové faktory MeSH
- dítě MeSH
- elektroretinografie metody MeSH
- lidé MeSH
- poruchy autistického spektra * MeSH
- retina MeSH
- světelná stimulace metody MeSH
- výzkumný projekt MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
