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2.
Elife ; 112022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36063381

RESUMO

Primary cilia are sensory membrane protrusions whose dysfunction causes ciliopathies. INPP5E is a ciliary phosphoinositide phosphatase mutated in ciliopathies like Joubert syndrome. INPP5E regulates numerous ciliary functions, but how it accumulates in cilia remains poorly understood. Herein, we show INPP5E ciliary targeting requires its folded catalytic domain and is controlled by four conserved ciliary localization signals (CLSs): LLxPIR motif (CLS1), W383 (CLS2), FDRxLYL motif (CLS3) and CaaX box (CLS4). We answer two long-standing questions in the field. First, partial CLS1-CLS4 redundancy explains why CLS4 is dispensable for ciliary targeting. Second, the essential need for CLS2 clarifies why CLS3-CLS4 are together insufficient for ciliary accumulation. Furthermore, we reveal that some Joubert syndrome mutations perturb INPP5E ciliary targeting, and clarify how each CLS works: (i) CLS4 recruits PDE6D, RPGR and ARL13B, (ii) CLS2-CLS3 regulate association to TULP3, ARL13B, and CEP164, and (iii) CLS1 and CLS4 cooperate in ATG16L1 binding. Altogether, we shed light on the mechanisms of INPP5E ciliary targeting, revealing a complexity without known parallels among ciliary cargoes.


Assuntos
Ciliopatias , Doenças Renais Císticas , Anormalidades Múltiplas , Cerebelo/anormalidades , Cílios/metabolismo , Anormalidades do Olho , Proteínas do Olho/metabolismo , Humanos , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Retina/anormalidades
3.
Nat Commun ; 13(1): 5218, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064789

RESUMO

The superior colliculus is a midbrain structure that plays important roles in visually guided behaviors in mammals. Neurons in the superior colliculus receive inputs from retinal ganglion cells but how these inputs are integrated in vivo is unknown. Here, we discovered that high-density electrodes simultaneously capture the activity of retinal axons and their postsynaptic target neurons in the superior colliculus, in vivo. We show that retinal ganglion cell axons in the mouse provide a single cell precise representation of the retina as input to superior colliculus. This isomorphic mapping builds the scaffold for precise retinotopic wiring and functionally specific connection strength. Our methods are broadly applicable, which we demonstrate by recording retinal inputs in the optic tectum in zebra finches. We find common wiring rules in mice and zebra finches that provide a precise representation of the visual world encoded in retinal ganglion cells connections to neurons in retinorecipient areas.


Assuntos
Células Ganglionares da Retina , Colículos Superiores , Animais , Axônios/fisiologia , Eletrodos , Mamíferos , Camundongos , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Colículos Superiores/fisiologia , Vias Visuais/fisiologia
4.
PLoS One ; 17(9): e0273633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36067194

RESUMO

INTRODUCTION: Diabetic retinopathy (DR) is one of the major complications of diabetes mellitus and is a significant cause of blindness worldwide. In Uganda, the prevalence of diabetes is approximately 2.7% of the urban population and 1% in rural areas. Many diabetics cannot access an eye exam due to the lack of less costly and user-friendly equipment that primary eye workers can use. Smartphone-based fundus photography allows for a cheap and mobile fundus examination. The study aimed to determine the sensitivity and specificity of the Portable Eye Examination Kit (PEEK) retina compared to a standard ophthalmic fundus camera (Zeiss Visucam 200) for the diagnosis of DR. METHODS: From January-March 2020, 286 people with diabetes (type 1 & 2) patients were seen at Kiruddu National referral hospital diabetes clinic. All participants had funduscopy with PEEK retina and the standard ophthalmic fundus camera following ophthalmic examination and pupillary dilation. The PEEK retina's sensitivity, specificity and reliability were determined using an ophthalmic fundus camera as the gold standard. RESULTS: The participants' mean age was 51 with a standard deviation of ±11years, 213 (74.5%) were females, and the majority (93.4%) had Type 2 diabetes. The overall Sensitivity of PEEK retina for DR was 84% (95% CI 70.9-83.5), while the specificity was 79.9% (95% CI 76-83.5) with a positive predictive value (PPV) of 30.9% (95% CI 23.2-39.4) and a negative predictive value (NPV) of 97.9% (95% CI 95.9-99.1). CONCLUSIONS: PEEK retina has high sensitivity and specificity, making it suitable for screening and diagnostic purposes. Therefore, we recommend the integration of the PEEK retina in the screening and diagnosis of DR in resource-limited settings.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Benzofenonas , Estudos Transversais , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fotografação , Polímeros , Reprodutibilidade dos Testes , Retina/diagnóstico por imagem , Smartphone , Uganda/epidemiologia
5.
Comput Intell Neurosci ; 2022: 3585506, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072751

RESUMO

This study develops an accurate method based on the generative adversarial network (GAN) that targets the issue of the current discontinuity of micro vessel segmentation in the retinal segmentation images. The processing of images has become increasingly efficient since the advent of deep learning method. We have proposed an improved GAN combined with SE-ResNet and dilated inception block for the segmenting retinal vessels (SAD-GAN). The GAN model has been improved with respect to the following points. (1) In the generator, the original convolution block is replaced with SE-ResNet module. Furthermore, SE-Net can extract the global channel information, while concomitantly strengthening and weakening the key features and invalid features, respectively. The residual structure can alleviate the issue of gradient disappearance. (2) The inception block and dilated convolution are introduced into the discriminator, which enhance the transmission of features and expand the acceptance domain for improved extraction of the deep network features. (3) We have included the attention mechanism in the discriminator for combining the local features with the corresponding global dependencies, and for highlighting the interdependent channel mapping. SAD-GAN performs satisfactorily on public retina datasets. On DRIVE dataset, ROC_AUC and PR_AUC reach 0.9813 and 0.8928, respectively. On CHASE_DB1 dataset, ROC_AUC and PR_AUC reach 0.9839 and 0.9002, respectively. Experimental results demonstrate that the generative adversarial model, combined with deep convolutional neural network, enhances the segmentation accuracy of the retinal vessels far above that of certain state-of-the-art methods.


Assuntos
Processamento de Imagem Assistida por Computador , Vasos Retinianos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem
6.
J Neural Eng ; 19(5)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066085

RESUMO

Objective. Retinal electrical stimulation using multi-electrode arrays (MEAs) aims to restore visual object perception in blind patients. However, the rate and duration of the artificial visual sensations are limited due to the rapid response decay of the stimulated neurons. Hence, we investigated a novel nature-inspired saccadic-like stimulation paradigm (biomimetic) to evoke sustained retinal responses. For implementation, the macroelectrode was replaced by several contiguous microelectrodes and activated non-simultaneously but alternating topologically.Approach.MEAs with hexagonally arranged electrodes were utilized to simulate and record mouse retinal ganglion cells (RGCs). Two shapes were presented electrically using MEAs: a 6e-hexagon (six hexagonally arranged 10µm electrodes; 6e-hexagon diameter: 80µm) and a double-bar (180µm spaced, 320µm in length). Electrodes of each shape were activated in three different modes (simultaneous, circular, and biomimetic ('zig-zag')), stimulating at different frequencies (1-20 Hz).Main results.The biomimetic stimulation generated enhanced RGC responses increasing the activity rate by 87.78%. In the spatiotemporal context, the electrical representation of the 6e-hexagon produced sustained and local RGC responses (∼130µm corresponding to ∼2.5° of the human visual angle) for up to 90 s at 10 Hz stimulation and resolved the electrically presented double-bar. In contrast, during conventional simultaneous stimulation, the responses were poor and declined within seconds. Similarly, the applicability of the biomimetic mode for retinal implants (7 × 8 pixels) was successfully demonstrated. An object shape impersonating a smile was presented electrically, and the recorded data were used to emulate the implant's performance. The spatiotemporal pixel mapping of the activity produced a complete retinal image of the smile.Significance.The application of electrical stimulation in the biomimetic mode produced locally enhanced RGC responses with significantly reduced fading effects and yielded advanced spatiotemporal performance reflecting the presented electrode shapes in the mapped activity imprint. Therefore, it is likely that the RGC responses persist long enough to evoke visual perception and generate a seamless image, taking advantage of the flicker fusion. Hence, replacing the implant's macroelectrodes with microelectrodes and their activation in a topologically alternating biomimetic fashion may overcome the patient's perceptual image fading, thereby enhancing the spatiotemporal characteristics of artificial vision.


Assuntos
Células Ganglionares da Retina , Próteses Visuais , Potenciais de Ação/fisiologia , Animais , Estimulação Elétrica/métodos , Humanos , Camundongos , Microeletrodos , Retina , Células Ganglionares da Retina/fisiologia
7.
Eur Rev Med Pharmacol Sci ; 26(16): 5736-5744, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36066147

RESUMO

OBJECTIVE: The aim of the study was to quantify the macular vascular density and retinal thickness in the eyes of young myopic people with myopia without pathological changes using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this cross-sectional study, 160 eyes of 80 myopia subjects without pathological changes were classified into three groups: mild myopia (N=40 eyes), moderate myopia (N=66 eyes), and high myopia (N=54 eyes). Macular vascular density (VD), retinal thickness, area of the foveal avascular zone, the flow area of the outer retina and choriocapillaris (CC) were measured using OCTA. The effects of other confounding factors including axial length, the spherical equivalent, and some systemic factors (blood pressure, height, weight, etc.) were also considered. RESULTS: As the severity of myopia increases, the CC flow area decreased (p=0.029). The superficial VD in the temporal, superior, nasal, and inferior regions was significantly lower in high myopia group compared to moderate and low myopia groups (all p<0.001). With increasing myopia, a significant reduction of deep VD was found in the superior region of the macula (p=0.007). In the fovea, there was no difference in the superficial or deep VD across groups (p=0.268 and p=0.413, respectively). Parafoveal retinal thickness was thinnest in the high myopia group and thickest in the mild myopia group (all p<0.05). The fovea was thickest in the high myopia group and thinnest in the mild myopia group (p=0.030). CONCLUSIONS: In young myopic people without pathological changes, superficial VD and retinal thickness decreased with myopia progression, except in the fovea. The CC flow area decreased with increasing myopia.


Assuntos
Miopia , Tomografia de Coerência Óptica , Adulto , Angiografia/métodos , Estudos Transversais , Angiofluoresceinografia/métodos , Humanos , Densidade Microvascular , Miopia/patologia , Retina/diagnóstico por imagem , Retina/patologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos
8.
Biomed Pharmacother ; 149: 112911, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-36068774

RESUMO

This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myriad pathogenic mechanisms have been implicated in these disorders, common signaling pathways leading to apoptotic cell death to all of them, and to all neurodegenerative diseases are (i) calcium dyshomeostasis/excitotoxicity; (ii) oxidative stress/mitochondrial dysfunction, and (iii) neuroinflammation/P2X7 receptor activation. From a therapeutic point of view, it is relevant to consider the multitarget approach based on the use of combined medicines acting on complementary pathogenic mechanisms that has been highly successful in the treatment of chronic diseases such as cancer, AIDS, pain, hypertension, Parkinson's disease, cardiac failure, depression, or the epilepsies as the basic mechanisms of cell death do not differ between the different CNS degenerative diseases. We suggest the multi-target therapy approach could be more effective compared with single-drug treatments. Used at doses lower than standard, these triads may also be safer and more efficient. After the establishment of a proof-of-concept in animal models of retinal degeneration, potential successful preclinical trials of such combinations may eventually drive to test this concept in clinical trials in patients, first to evaluate the safety and efficacy of the drug combinations in humans and then their therapeutic advantages, if any, seeking the prevention and/or the delay of retina degeneration and blindness.


Assuntos
Retinopatia Diabética , Doenças Neurodegenerativas , Degeneração Retiniana , Animais , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Neuroproteção , Retina/metabolismo , Degeneração Retiniana/tratamento farmacológico
9.
Zhonghua Yan Ke Za Zhi ; 58(9): 731-735, 2022 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-36069100

RESUMO

Optical coherence tomography angiography (OCTA) is a new vascular imaging technology based on high-resolution optical coherence tomography image analysis. It can scan the moving red blood cells in blood vessels for three-dimensional imaging of human retinal and choroidal vessels. Since the close connection of vascular endothelial cells of the blood-retinal barrier is similar to that of the blood-brain barrier, the role of OCTA in the research of pathogenesis and course monitoring of a variety of central system diseases such as Alzheimer's disease, Parkinson's disease, stroke, migraine, multiple sclerosis and optic neuromyelitis has been widely discussed. This article reviews the application and progress of OCTA in central nervous system diseases.


Assuntos
Doenças do Sistema Nervoso Central , Tomografia de Coerência Óptica , Células Endoteliais , Angiofluoresceinografia/métodos , Humanos , Retina , Vasos Retinianos , Tomografia de Coerência Óptica/métodos
10.
Sci Rep ; 12(1): 14888, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050364

RESUMO

Deep learning methods have enabled a fast, accurate and automated approach for retinal layer segmentation in posterior segment OCT images. Due to the success of semantic segmentation methods adopting the U-Net, a wide range of variants and improvements have been developed and applied to OCT segmentation. Unfortunately, the relative performance of these methods is difficult to ascertain for OCT retinal layer segmentation due to a lack of comprehensive comparative studies, and a lack of proper matching between networks in previous comparisons, as well as the use of different OCT datasets between studies. In this paper, a detailed and unbiased comparison is performed between eight U-Net architecture variants across four different OCT datasets from a range of different populations, ocular pathologies, acquisition parameters, instruments and segmentation tasks. The U-Net architecture variants evaluated include some which have not been previously explored for OCT segmentation. Using the Dice coefficient to evaluate segmentation performance, minimal differences were noted between most of the tested architectures across the four datasets. Using an extra convolutional layer per pooling block gave a small improvement in segmentation performance for all architectures across all four datasets. This finding highlights the importance of careful architecture comparison (e.g. ensuring networks are matched using an equivalent number of layers) to obtain a true and unbiased performance assessment of fully semantic models. Overall, this study demonstrates that the vanilla U-Net is sufficient for OCT retinal layer segmentation and that state-of-the-art methods and other architectural changes are potentially unnecessary for this particular task, especially given the associated increased complexity and slower speed for the marginal performance gains observed. Given the U-Net model and its variants represent one of the most commonly applied image segmentation methods, the consistent findings across several datasets here are likely to translate to many other OCT datasets and studies. This will provide significant value by saving time and cost in experimentation and model development as well as reduced inference time in practice by selecting simpler models.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Retina/diagnóstico por imagem
11.
Rom J Morphol Embryol ; 63(1): 121-127, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074675

RESUMO

The aim of the study was to better understand the interplay between genetic factors and the aging process in the human retina through mapping complement factor H (CFH) and related proteins. Two human eyes, from 92- and 64-year-old donors, were genotyped for the expression of CFH-related 1 (CFHR1) and CFH-related 3 (CFHR3) genes. Deoxyribonucleic acid (DNA) was extracted and analyzed for concentration and purity with a spectrophotometer, at 260 nm. The results showed a DNA concentration of 469.17 ng∕µL in the aged retina and of 399.20 ng∕µL in the younger one. Through polymerase chain reaction (PCR) genotyping, the DNA CFHR1 and CFHR3 were visible as bands of 175 bp and 181 bp. Immunohistochemistry by immunofluorescence method was used with a panel of specific antibodies for CFH, CFHR1, CFHR3 and GFAP, a marker for Müller cells. All the samples were examined, and images captured using confocal microscopy. In the younger retina, CFH was localized in the inner plexiform layer and below the outer nuclear layer, while in the aged retina, it was found in the photoreceptors. CFH was also detected in the choriocapillaris and within the end-feet of the Müller cells. Our controls showed autofluorescence of the retinal pigment epithelium shedding light on a false positive CFH immunostaining of this layer. GFAP immunoreactivity highlighted an increased gliosis within the aged retina. CFHR3 signal was found in the microglia, while CFHR1 was detected in the choriocapillaris. In summary, underpinning the expression of these components can show the potential involvement of these modulators in implementing new treatment strategies.


Assuntos
Envelhecimento , Proteínas Inativadoras do Complemento C3b , Idoso , Envelhecimento/genética , Biomarcadores , Proteínas Inativadoras do Complemento C3b/genética , Proteínas Inativadoras do Complemento C3b/metabolismo , DNA , Genótipo , Humanos , Retina
12.
Rom J Morphol Embryol ; 63(1): 213-219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074687

RESUMO

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to optic atrophy due to degeneration of the retinal ganglion cell. A curative treatment is not available at the moment, but a new antioxidant drug, Idebenone, is expected to reduce the progression of the disorder. Two male patients, genetically confirmed with LHON, were clinically, morphologically, and electrophysiologically evaluated, before and three, six, nine and 12 months after starting the treatment. The patient with 3460G>A mutation in mitochondrially-encoded nicotinamide adenine dinucleotide, reduced form (NADH):ubiquinone oxidoreductase core subunit (mtND)1 gene showed an improvement in visual acuity, visual field, and visual evoked potentials with no effect on morphological examinations, while the patient with 11778G>A mutation in mtND4 gene showed no functional, nor morphological recovery after one year of treatment. This study demonstrates that Idebenone, depending on the genetic profile of the disease, may be effective in functional improvement in patients with LHON.


Assuntos
Atrofia Óptica Hereditária de Leber , Potenciais Evocados Visuais , Humanos , Masculino , Atrofia Óptica Hereditária de Leber/tratamento farmacológico , Atrofia Óptica Hereditária de Leber/genética , Retina , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
13.
Sci Rep ; 12(1): 15160, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071126

RESUMO

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified. The ipRGCs with somas in the ganglion cell layer have been studied extensively, but less is known about those with somas in the inner nuclear layer, the "displaced" cells. To investigate their synaptic inputs, three sets of horizontal, ultrathin sections through central macaque retina were collected using serial block-face scanning electron microscopy. One displaced ipRGC received nearly all of its excitatory inputs from ON bipolar cells and would therefore be expected to have ON responses to light. In each of the three volumes, there was also at least one cell that had a large soma in the inner nuclear layer, varicose axons and dendrites with a large diameter that formed large, extremely sparse arbor in the outermost stratum of the inner plexiform layer. They were identified as the displaced M1 type of ipRGCs based on this morphology and on the high density of granules in their somas. They received extensive input from amacrine cells, including the dopaminergic type. The vast majority of their excitatory inputs were from OFF bipolar cells, including two subtypes with extensive input from the primary rod pathway. They would be expected to have OFF responses to light stimuli below the threshold for melanopsin or soon after the offset of a light stimulus.


Assuntos
Macaca , Retina , Células Amácrinas/metabolismo , Animais , Gânglios , Retina/metabolismo , Células Ganglionares da Retina/metabolismo
14.
Transl Vis Sci Technol ; 11(9): 3, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36053140

RESUMO

Purpose: We employ visible light optical coherence tomography (OCT) to investigate the relationship between the myoid, ellipsoid, and band 2 in the living human retina. Rather than refute existing theories, we aim to reveal new bands and better delineate the structures at hand. Methods: An upgraded spectral/Fourier domain visible light OCT prototype, with 1.0-µm axial resolution, imaged 13 eyes of 13 young adult human subjects (23-40 years old) without a history of ocular pathology. The external limiting membrane (band 1) and band 2 edges were segmented. Reflectivity was examined along the inner segment (IS), defined as extending from band 1 to the band 2 center, and within band 2 itself. Results: Images highlight a nearly continuously resolved extrafoveal internal limiting membrane, the peripheral single-cell thick ganglion cell layer, and the peripheral photoreceptor axonal fiber layer, a peripheral division of band 2 into bands 2a and 2b, and a reflectivity-based division of the IS into "m" and "e" zones. Discussion: Topography and transverse intensity variations of the outermost band 2b suggest an association with rods. The "m" and "e" zone border is consistent with the myoid-ellipsoid boundary, even recapitulating the well-documented distribution of mitochondria throughout the IS at the foveal center. Theories of outer retinal reflectivity in OCT must adequately explain these observations. Translational Relevance: Findings support that band 2 does partially overlap with the ellipsoid in transversally averaged OCT images due to photoreceptor IS length dispersion but argue that the inner ellipsoid must be inner to band 2, as suggested by prior quantitative measurements.


Assuntos
Retina , Tomografia de Coerência Óptica , Adulto , Humanos , Luz , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto Jovem
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(8): 1075-1081, 2022 Aug 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36097775

RESUMO

OBJECTIVES: Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. METHODS: Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. RESULTS: Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). CONCLUSIONS: The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.


Assuntos
Coriorretinopatia Serosa Central , Coriorretinopatia Serosa Central/diagnóstico por imagem , Angiofluoresceinografia/métodos , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Retina , Tomografia de Coerência Óptica/métodos
16.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077078

RESUMO

Activation of NF-κB transcription factor is strictly regulated to accurately direct cellular processes including inflammation, immunity, and cell survival. In the retina, the modulation of the NF-κB pathway is essential to prevent excessive inflammatory responses, which plays a pivotal role in many retinal neurodegenerative diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and inherited retinal dystrophies (IRDs). A critical cytokine mediating inflammatory responses in retinal cells is tumor necrosis factor-alpha (TNFα), leading to the activation of several transductional pathways, including NF-κB. However, the multiple factors orchestrating the appropriate regulation of NF-κB in retinal cells still remain unclear. The present study explores how the ubiquitin-specific protease 48 (USP48) downregulation impacts the stability and transcriptional activity of NF-κB/p65 in retinal pigment epithelium (RPE), at both basal conditions and following TNFα stimulation. We described that USP48 downregulation stabilizes p65. Notably, the accumulation of p65 is mainly detectable in the nuclear compartment and it is accompanied by an increased NF-κB transcriptional activity. These results delineate a novel role of USP48 in negatively regulating NF-κB in retinal cells, providing new opportunities for therapeutic intervention in retinal pathologies.


Assuntos
NF-kappa B , Epitélio Pigmentado da Retina , NF-kappa B/metabolismo , Retina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo
17.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077087

RESUMO

Embryonic hyperglycemia negatively impacts retinal development, leading to abnormal visual behavior, altered timing of retinal progenitor differentiation, decreased numbers of retinal ganglion cells and Müller glia, and vascular leakage. Because synaptic disorganization is a prominent feature of many neurological diseases, the goal of the current work was to study the potential impact of hyperglycemia on retinal ribbon synapses during embryonic development. Our approach utilized reverse transcription quantitative PCR (RT-qPCR) and immunofluorescence labeling to compare the transcription of synaptic proteins and their localization in hyperglycemic zebrafish embryos, respectively. Our data revealed that the maturity of synaptic ribbons was compromised in hyperglycemic zebrafish larvae, where altered ribeye expression coincided with the delay in establishing retinal ribbon synapses and an increase in the immature synaptic ribbons. Our results suggested that embryonic hyperglycemia disrupts retinal synapses by altering the development of the synaptic ribbon, which can lead to visual defects. Future studies using zebrafish models of hyperglycemia will allow us to study the underlying mechanisms of retinal synapse development.


Assuntos
Hiperglicemia , Peixe-Zebra , Animais , Hiperglicemia/metabolismo , Retina/metabolismo , Sinapses/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
18.
Annu Rev Vis Sci ; 8: 79-99, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36108104

RESUMO

The vertebrate retina is regarded as a simple part of the central nervous system (CNS) and thus amenable to investigations of the determinants of cell fate. Its five neuronal cell classes and one glial cell class all derive from a common pool of progenitors. Here we review how each cell class is generated. Retinal progenitors progress through different competence states, in each of which they generate only a small repertoire of cell classes. The intrinsic state of the progenitor is determined by the complement of transcription factors it expresses. Thus, although progenitors are multipotent, there is a bias in the types of fates they generate during any particular time window. Overlying these competence states are stochastic mechanisms that influence fate decisions. These mechanisms are determined by a weighted set of probabilities based on the abundance of a cell class in the retina. Deterministic mechanisms also operate, especially late in development, when preprogrammed progenitors solely generate specific fates.


Assuntos
Retina , Células-Tronco , Diferenciação Celular/fisiologia , Neurônios , Retina/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo
19.
BMC Bioinformatics ; 23(1): 378, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114457

RESUMO

BACKGROUND: The retina is a complex tissue containing multiple cell types that are essential for vision. Understanding the gene expression patterns of various retinal cell types has potential applications in regenerative medicine. Retinal organoids (optic vesicles) derived from pluripotent stem cells have begun to yield insights into the transcriptomics of developing retinal cell types in humans through single cell RNA-sequencing studies. Previous methods of gene reporting have relied upon techniques in vivo using microarray data, or correlational and dimension reduction methods for analyzing single cell RNA-sequencing data computationally. We aimed to develop a state-of-the-art Boolean method that filtered out noise, could be applied to a wide variety of datasets and lent insight into gene expression over differentiation. RESULTS: Here, we present a bioinformatic approach using Boolean implication to discover genes which are retinal cell type-specific or involved in retinal cell fate. We apply this approach to previously published retina and retinal organoid datasets and improve upon previously published correlational methods. Our method improves the prediction accuracy of marker genes of retinal cell types and discovers several new high confidence cone and rod-specific genes. CONCLUSIONS: The results of this study demonstrate the benefits of a Boolean approach that considers asymmetric relationships. We have shown a statistically significant improvement from correlational, symmetric methods in the prediction accuracy of retinal cell-type specific genes. Furthermore, our method contains no cell or tissue-specific tuning and hence could impact other areas of gene expression analyses in cancer and other human diseases.


Assuntos
Células-Tronco Pluripotentes , Retina , Diferenciação Celular/genética , Humanos , Organoides/metabolismo , Células-Tronco Pluripotentes/metabolismo , RNA/metabolismo
20.
Stem Cell Res Ther ; 13(1): 478, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114559

RESUMO

BACKGROUND: Human-induced pluripotent stem cell-derived retinal organoids are a valuable tool for disease modelling and therapeutic development. Many efforts have been made over the last decade to optimise protocols for the generation of organoids that correctly mimic the human retina. Most protocols use common media supplements; however, protocol-dependent variability impacts data interpretation. To date, the lack of a systematic comparison of a given protocol with or without supplements makes it difficult to determine how they influence the differentiation process and morphology of the retinal organoids. METHODS: A 2D-3D differentiation method was used to generate retinal organoids, which were cultured with or without the most commonly used media supplements, notably retinoic acid. Gene expression was assayed using qPCR analysis, protein expression using immunofluorescence studies, ultrastructure using electron microscopy and 3D morphology using confocal and biphoton microscopy of whole organoids. RESULTS: Retinoic acid delayed the initial stages of differentiation by modulating photoreceptor gene expression. At later stages, the presence of retinoic acid led to the generation of mature retinal organoids with a well-structured stratified photoreceptor layer containing a predominant rod population. By contrast, the absence of retinoic acid led to cone-rich organoids with a less organised and non-stratified photoreceptor layer. CONCLUSIONS: This study proves the importance of supplemented media for culturing retinal organoids. More importantly, we demonstrate for the first time that the role of retinoic acid goes beyond inducing a rod cell fate to enhancing the organisation of the photoreceptor layer of the mature organoid.


Assuntos
Células-Tronco Pluripotentes Induzidas , Organoides , Diferenciação Celular , Humanos , Organoides/metabolismo , Retina/metabolismo , Tretinoína/farmacologia
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