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Background: Silicone oil is used as endotamponade following vitreoretinal surgery to maintain the retina reattached when indicated. This study investigates the hypothesis that silicone oil causes insulation effects on the retina by affecting its response to light. Methods: Electrophysiological responses to a flash stimulus were recorded using full-field electroretinography (ERG) and visual evoked potentials (VEP). Recordings were performed in 9 patients who underwent surgery for retinal detachment, before (12 days) and after (23 weeks) silicone oil removal (SOR) in both the study and the control eye. Flash ERG and VEP recordings were performed according to the ISCEV standard protocol. Results: Statistically significant differences were found in the study eye in the amplitudes of the ERG responses and their corresponding ratios, i.e. the amplitude after SOR over the amplitude before SOR, in all conditions tested. No differences were observed in the control eye. The mean ratio of photopic ERG response was 3.4 ± 2.4 for the study and 1.0 ± 0.3 for the control eye (p<0.001). The mean ratio of ERG flicker response was 3.1 ± 2.4 and 1.0 ± 0.3, respectively (p = 0.003). Scotopic flash ERG ratio was 5.0 ± 4.4 for the study and 1.3 ± 0.6 for the control eye (p = 0.012). No differences were observed for the amplitude and latency of flash VEP response after SOR. Conclusions: Silicone oil causes a reduction in flash ERG responses; no effect was found on flash VEP responses. ERGs in eyes filled with silicone oil should not be considered representative of retinal functionality, in contrast to VEPs, which are not affected by silicone oil presence.(AU)
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Humanos , Masculino , Feminino , Descolamento Retiniano/cirurgia , Óleos de Silicone/administração & dosagem , Óleos de Silicone/efeitos adversos , Eletrorretinografia , Cirurgia Vitreorretiniana , Optometria , Visão Ocular , Retina/cirurgia , Potenciais Evocados VisuaisRESUMO
Glaucoma leads to vision loss due to retinal ganglion cell death. Astrocyte reactivity contributes to neurodegeneration. Our recent study found that lipoxin B4 (LXB4), produced by retinal astrocytes, has direct neuroprotective actions on retinal ganglion cells. In this study, we aimed to investigate how the autacoid LXB4 influences astrocyte reactivity in the retina under inflammatory cytokine-induced activation and during ocular hypertension. The protective activity of LXB4 was investigated in vivo using the mouse silicone-oil model of chronic ocular hypertension. By employing a range of analytical techniques, including bulk RNA-seq, RNAscope in-situ hybridization, qPCR, and lipidomic analyses, we discovered the formation of lipoxins and expression of the lipoxin pathway in rodents (including the retina and optic nerve), primates (optic nerve), and human brain astrocytes, indicating the presence of this neuroprotective pathway across various species. Findings in the mouse retina identified significant dysregulation of the lipoxin pathway in response to chronic ocular hypertension, leading to an increase in 5-lipoxygenase (5-LOX) activity and a decrease in 15-LOX activity. This dysregulation was coincident with a marked upregulation of astrocyte reactivity. Reactive human brain astrocytes also showed a significant increase in 5-LOX. Treatment with LXB4 amplified the lipoxin biosynthetic pathway by restoring and amplifying the generation of another member of the lipoxin family, LXA4, and mitigated astrocyte reactivity in mouse retinas and human brain astrocytes. In conclusion, the lipoxin pathway is functionally expressed in rodents, primates, and human astrocytes, and is a resident neuroprotective pathway that is downregulated in reactive astrocytes. Novel cellular targets for LXB4's neuroprotective action are inhibition of astrocyte reactivity and restoration of lipoxin generation. Amplifying the lipoxin pathway is a potential target to disrupt or prevent astrocyte reactivity in neurodegenerative diseases, including retinal ganglion cell death in glaucoma.
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Glaucoma , Lipoxinas , Hipertensão Ocular , Humanos , Animais , Camundongos , Lipoxinas/farmacologia , Astrócitos , Citocinas , Retina , Modelos Animais de Doenças , PrimatasRESUMO
Purpose: This study aims to examine the short-term peripheral choroidal thickness (PChT) response to signed defocus blur, both with and without native peripheral aberrations. This examination will provide insights into the role of peripheral aberration in detecting signs of defocus. Methods: The peripheral retina (temporal 15°) of the right eye was exposed to a localized video stimulus in 11 young adults. An adaptive optics system induced 2D myopic or hyperopic defocus onto the stimulus, with or without correcting native peripheral ocular aberrations (adaptive optics [AO] or NoAO defocus conditions). Choroidal scans were captured using Heidelberg Spectralis OCT at baseline, exposure (10, 20, and 30 minutes), and recovery phases (4, 8, and 15 minutes). Neural network-based automated MATLAB segmentation program measured PChT changes from OCT scans, and statistical analysis evaluated the effects of different optical conditions over time. Results: During the exposure phase, NoAO myopic and hyperopic defocus conditions exhibited distinct bidirectional PChT alterations, showing average thickening (10.0 ± 5.3 µm) and thinning (-9.1 ± 5.5 µm), respectively. In contrast, induced AO defocus conditions did not demonstrate a significant change from baseline. PChT recovery to baseline occurred for all conditions. The unexposed fovea did not show any significant ChT change, indicating a localized ChT response to retinal blur. Conclusions: We discovered that the PChT response serves as a marker for detecting peripheral retinal myopic and hyperopic defocus blur, especially in the presence of peripheral aberrations. These findings highlight the significant role of peripheral oriented blur in cueing peripheral defocus sign detection.
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Hiperopia , Miopia , Adulto Jovem , Humanos , Miopia/diagnóstico , Hiperopia/diagnóstico , Corioide , Retina , Fóvea Central , Refração OcularRESUMO
Purpose: This study aims to determine whether OCT-derived rates of change in minimum rim width (MRW) are associated with and can potentially predict corresponding alterations in retinal nerve fiber layer thickness (RNFLT) in people with glaucoma. Methods: The rates of change between six-monthly visits were taken from 568 eyes of 278 participants in the P3 Study. Structural equation models (SEM) assessed whether one parameter was predicted by the concurrent or previous rate of the other parameter, after adjusting for its own rate in the previous time interval. Root mean square error of approximation (RMSEA, with 90% confidence intervals [CI]), Tucker Lewis index (TLI) and the comparative fit index (CFI) assessed goodness of fit. Results: Models without a time lag provided a better fit for the data (RMSEA = 0.101 [CI, 0.089, 0.113]), compared to a model featuring a time lag in RNFLT (RMSEA = 0.114 [CI, 0.102, 0.126]) or MRW (RMSEA = 0.114 [CI, 0.102, 0.127]). The SEMs indicated that rates for both MRW and RNFLT were predicted by their own rate in the previous time interval and by the other measure's change in the concurrent time interval (P > 0.001 for all). No evidence of a clinically significant time lag for either parameter was determined. Conclusions: MRW and RNFLT exhibit concurrent changes over time in patients with glaucoma, with no clinically significant time lag determined. Translational Relevance: RNFLT may be more useful than MRW in early glaucoma assessment because of its previously reported lower variability and reduced sensitivity to intraocular pressure changes.
Assuntos
Glaucoma , Disco Óptico , Humanos , Disco Óptico/diagnóstico por imagem , Células Ganglionares da Retina , Fibras Nervosas , Retina , Glaucoma/diagnóstico , Tomografia de Coerência ÓpticaRESUMO
Melatonin is an important player in the regulation of many physiological functions within the body and in the retina. Melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Retinal melatonin is primarily synthesized by the photoreceptors, but whether the synthesis occurs in the rods and/or cones is still unclear. Melatonin exerts its influence by binding to G protein-coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Studies in rodents have shown that melatonin signaling plays an important role in the regulation of retinal dopamine levels, rod/cone coupling as well as the photopic and scotopic electroretinogram. In addition, melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor viability during aging and other studies have implicated melatonin in the pathogenesis of age-related macular degeneration. Hence melatonin may represent a useful tool in the fight to protect photoreceptors-and other retinal cells-against degeneration due to aging or diseases.
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Melatonina , Animais , Melatonina/metabolismo , Neuroproteção , Retina/metabolismo , Receptores de Melatonina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Mamíferos/metabolismoRESUMO
BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.
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Retinopatia Diabética , Retina , Humanos , Retinopatia Diabética/genética , Células Epiteliais , Pigmentos da Retina , GlucoseRESUMO
Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Early diagnosis is critical for patients to benefit from potential intervention and treatment. The retina has emerged as a plausible diagnostic site for AD detection owing to its anatomical connection with the brain. However, existing AI models for this purpose have yet to provide a rational explanation behind their decisions and have not been able to infer the stage of the disease's progression. Along this direction, we propose a novel model-agnostic explainable-AI framework, called Granu la ̲ r Neuron-le v ̲ el Expl a ̲ iner (LAVA), an interpretation prototype that probes into intermediate layers of the Convolutional Neural Network (CNN) models to directly assess the continuum of AD from the retinal imaging without the need for longitudinal or clinical evaluations. This innovative approach aims to validate retinal vasculature as a biomarker and diagnostic modality for evaluating Alzheimer's Disease. Leveraged UK Biobank cognitive tests and vascular morphological features demonstrate significant promise and effectiveness of LAVA in identifying AD stages across the progression continuum.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/diagnóstico por imagem , Fundo de Olho , Retina/diagnóstico por imagem , Neurônios , Imageamento por Ressonância MagnéticaRESUMO
Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.
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Retinopatia da Prematuridade , Fator A de Crescimento do Endotélio Vascular , Recém-Nascido , Humanos , Peso ao Nascer , Hemodinâmica , Retina , Retinopatia da Prematuridade/diagnóstico por imagemRESUMO
Crumbs homolog 1 (CRB1) is one of the key genes linked to retinitis pigmentosa and Leber congenital amaurosis, which are characterized by a high clinical heterogeneity. The Crumbs family member CRB2 has a similar protein structure to CRB1, and in zebrafish, Crb2 has been shown to interact through the extracellular domain. Here, we show that CRB1 and CRB2 co-localize in the human retina and human iPSC-derived retinal organoids. In retina-specific pull-downs, CRB1 was enriched in CRB2 samples, supporting a CRB1-CRB2 interaction. Furthermore, novel interactors of the crumbs complex were identified, representing a retina-derived protein interaction network. Using co-immunoprecipitation, we further demonstrate that human canonical CRB1 interacts with CRB1 and CRB2, but not with CRB3, which lacks an extracellular domain. Next, we explored how missense mutations in the extracellular domain affect CRB1-CRB2 interactions. We observed no or a mild loss of CRB1-CRB2 interaction, when interrogating various CRB1 or CRB2 missense mutants in vitro. Taken together, our results show a stable interaction of human canonical CRB2 and CRB1 in the retina.
Assuntos
Amaurose Congênita de Leber , Retinite Pigmentosa , Animais , Humanos , Peixe-Zebra/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Retina/metabolismo , Retinite Pigmentosa/genética , Retinite Pigmentosa/metabolismo , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Transporte/metabolismoRESUMO
Purpose: To describe and evaluate a novel method to determine the validity of measurements made using cycle-by-cycle (CxC) recording techniques in patients with advanced retinal degenerations (RD) having low-amplitude flicker electroretinogram (ERG) responses. Methods: The method extends the original CxC recording algorithm introduced by Sieving et al., retaining the original recording setup and the preliminary analysis of raw data. Novel features include extended use of spectrum analysis, reduction of errors due to known sources, and a comprehensive statistical assessment using three different tests. The method was applied to ERG recordings from seven patients with RD and two patients with CNGB3 achromatopsia. Results: The method was implemented as a Windows application to processes raw data obtained from a commercial ERG system, and it features a computational toolkit for statistical assessment of ERG recordings with amplitudes as low as 1 µV, commonly found in advanced RD patients. When recorded using conditions specific for eliciting cone responses, none of the CNGB3 patients had a CxC validated response, indicating that no signal artifacts were present with our recording conditions. A comparison of the presented method with conventional 30 Hz ERG was performed. Bland-Altman plots indicated good agreement (mean difference, -0.045 µV; limits of agreement, 0.193 to -0.282 µV) between the resulting amplitudes. Within-session test-retest variability was 15%, comparing favorably to the variability of standard ERG amplitudes. Conclusions: This novel method extracts highly reliable clinical recordings of low-amplitude flicker ERGs and effectively detects artifactual responses. It has potential value both as a cone outcome variable and planning tool in clinical trials on natural history and treatment of advanced RDs.
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Defeitos da Visão Cromática , Degeneração Retiniana , Humanos , Eletrorretinografia/métodos , Degeneração Retiniana/diagnóstico , Células Fotorreceptoras Retinianas Cones/fisiologia , Estimulação Luminosa , Retina/fisiologiaRESUMO
Purpose: This study investigates the temporal relationship between blood flow changes and alterations in retinal nerve fiber layer thickness (RNFLT) and mean deviation (MD) in individuals with glaucoma. Methods: Blood flow, measured by mean blur rate in optic nerve head vessels (MBRv) and tissues (MBRt) using laser speckle flowgraphy (LSFG)-NAVI, was analyzed using structural equation models (SEMs). SEMs assessed whether the previous rate of one parameter predicted the current rate of the other parameter, adjusted for its own rate in the previous time interval. Data from 345 eyes of 174 participants were gathered from visits every six months. Results: Rates of change of both MBRv and MBRt were significantly predicted by their own rate in the previous time interval and by the rate of change of MD in the previous time interval (P < 0.001 and P = 0.043, respectively), but not by the rate of MD in the concurrent interval (P = 0.947 and P = 0.549), implying that changes in MD precede changes in blood flow. Rates of change of RNFLT were predicted by their own previous rate and the rate of change of MBRv and MBRt in either the previous interval (P = 0.002 and P = 0.008) or the concurrent interval (P = 0.001 and P = 0.018), suggesting that MBR may change before RNFLT. Conclusions: The evidence supports a temporal sequence where MD changes precede blood flow changes, which, in turn, may precede alterations in RNFLT.
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Glaucoma , Disco Óptico , Humanos , Campos Visuais , Retina , Fibras NervosasRESUMO
Purpose: The purpose of this study was to evaluate the effects of posterior vitreous detachment (PVD) on visual quality in patients with high myopia, as well as investigate the associated factors of photopic and mesopic contrast sensitivity function (CSF) in high myopia. Methods: Visual quality was comprehensively assessed in patients with high myopia. Visual acuity, contrast sensitivity (CS) at four spatial frequencies (3, 6, 12, and 18 cycles per degree [c.p.d.]) under photopic and mesopic conditions, as well as the modulation transfer function cutoff value (MTFcutoff), the objective scatter index (OSI), the Strehl ratio (SR), and internal aberrations, were measured in this cross-sectional study. Results: This study included 94 eyes from 47 subjects with bilateral high myopia, including 23 eyes with complete PVD (cPVD), 21 eyes with partial PVD (pPVD), and 50 eyes without PVD (nPVD). There was no significant difference in visual quality between the cPVD group and the nPVD group. Whereas in eyes with pPVD, there was a degradation of overall photopic CSF (versus nPVD, P = 0.048), photopic CS at 3 c.p.d. (versus cPVD, P = 0.009 and versus nPVD, P = 0.032), photopic CS at 18 c.p.d. (versus nPVD, P = 0.033), overall mesopic CSF (versus nPVD, P = 0.033), and secondary astigmatism (versus cPVD, P = 0.044). Under photopic conditions, the factors affecting CSF were pPVD and SR, whereas the factors affecting mesopic CSF were pPVD, OSI, and ganglion cell-inner plexiform layer thickness. Conclusions: The pPVD impaired visual quality in patients with high myopia compared to nPVD or cPVD, and pPVD could be a factor explaining CSF at both photopic and mesopic illumination. Translational Relevance: Clinicians need to closely monitor patients with high myopia with pPVD due to the potential decline in visual quality and the development of vitreoretinal disorders.
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Miopia , Descolamento do Vítreo , Humanos , Sensibilidades de Contraste , Estudos Transversais , Miopia/complicações , Miopia/diagnóstico , RetinaRESUMO
Purpose: No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Methods: Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery. Results: RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Conclusions: Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.
Assuntos
Neovascularização de Coroide , Atrofia Geográfica , Degeneração Macular , Feminino , Suínos , Animais , Desbridamento , Degeneração Macular/diagnóstico , Degeneração Macular/cirurgia , Atrofia Geográfica/diagnóstico , Sus scrofa , Retina , Corioide , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/cirurgiaRESUMO
Purpose: The assessment of retinal image (RI) quality holds significant importance in both clinical trials and large datasets, because suboptimal images can potentially conceal early signs of diseases, thereby resulting in inaccurate medical diagnoses. This study aims to develop an automatic method for Retinal Image Quality Assessment (RIQA) that incorporates visual explanations, aiming to comprehensively evaluate the quality of retinal fundus images (RIs). Methods: We developed an automatic RIQA system, named Swin-MCSFNet, utilizing 28,792 RIs from the EyeQ dataset, as well as 2000 images from the EyePACS dataset and an additional 1,000 images from the OIA-ODIR dataset. After preprocessing, including cropping black regions, data augmentation, and normalization, a Swin-MCSFNet classifier based on the Swin-Transformer for multiple color-space fusion was proposed to grade the quality of RIs. The generalizability of Swin-MCSFNet was validated across multiple data centers. Additionally, for enhanced interpretability, a Score-CAM-generated heatmap was applied to provide visual explanations. Results: Experimental results reveal that the proposed Swin-MCSFNet achieves promising performance, yielding a micro-receiver operating characteristic (ROC) of 0.93 and ROC scores of 0.96, 0.81, and 0.96 for the "Good," "Usable," and "Reject" categories, respectively. These scores underscore the accuracy of RIQA based on Swin-MCSF in distinguishing among the three categories. Furthermore, heatmaps generated across different RIQA classification scores and various color spaces suggest that regions in the retinal images from multiple color spaces contribute significantly to the decision-making process of the Swin-MCSFNet classifier. Conclusions: Our study demonstrates that the proposed Swin-MCSFNet outperforms other methods in experiments conducted on multiple datasets, as evidenced by the superior performance metrics and insightful Score-CAM heatmaps. Translational Relevance: This study constructs a new retinal image quality evaluation system, which will contribute to the subsequent research of retinal images.
Assuntos
Retina , Fundo de Olho , Retina/diagnóstico por imagemRESUMO
VGluT3-expressing mouse retinal amacrine cells (VG3s) respond to small-object motion and connect to multiple types of bipolar cells (inputs) and retinal ganglion cells (RGCs, outputs). Because these input and output connections are intermixed on the same dendrites, making sense of VG3 circuitry requires comparing the distribution of synapses across their arbors to the subcellular flow of signals. Here, we combine subcellular calcium imaging and electron microscopic connectomic reconstruction to analyze how VG3s integrate and transmit visual information. VG3s receive inputs from all nearby bipolar cell types but exhibit a strong preference for the fast type 3a bipolar cells. By comparing input distributions to VG3 dendrite responses, we show that VG3 dendrites have a short functional length constant that likely depends on inhibitory shunting. This model predicts that RGCs that extend dendrites into the middle layers of the inner plexiform encounter VG3 dendrites whose responses vary according to the local bipolar cell response type.
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Células Amácrinas , Retina , Camundongos , Animais , Células Amácrinas/fisiologia , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Sinapses/metabolismo , Microscopia Eletrônica , Dendritos/fisiologiaRESUMO
Despite the conservation of genetic machinery involved in eye development, there is a strong diversity in the placement of eyes on the head of animals. Morphogen gradients of signaling molecules are vital to patterning cues. During Drosophila eye development, Wingless (Wg), a ligand of Wnt/Wg signaling, is expressed anterolaterally to form a morphogen gradient to determine the eye- versus head-specific cell fate. The underlying mechanisms that regulate this process are yet to be fully understood. We characterized defective proventriculus (dve) (Drosophila ortholog of human SATB1), a K50 homeodomain transcription factor, as a dorsal eye gene, which regulates Wg signaling to determine eye versus head fate. Across Drosophila species, Dve is expressed in the dorsal head vertex region where it regulates wg transcription. Second, Dve suppresses eye fate by down-regulating retinal determination genes. Third, the dve-expressing dorsal head vertex region is important for Wg-mediated inhibition of retinal cell fate, as eliminating the Dve-expressing cells or preventing Wg transport from these dve-expressing cells leads to a dramatic expansion of the eye field. Together, these findings suggest that Dve regulates Wg expression in the dorsal head vertex, which is critical for determining eye versus head fate. Gain-of-function of SATB1 exhibits an eye fate suppression phenotype similar to Dve. Our data demonstrate a conserved role for Dve/SATB1 in the positioning of eyes on the head and the interocular distance by regulating Wg. This study provides evidence that dysregulation of the Wg morphogen gradient results in developmental defects such as hypertelorism in humans where disproportionate interocular distance and facial anomalies are reported.
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Proteínas de Drosophila , Proteínas de Ligação à Região de Interação com a Matriz , Animais , Humanos , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Proteína Wnt1/genética , Proteína Wnt1/metabolismo , Drosophila/genética , Retina/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Drosophila melanogaster/metabolismo , Padronização Corporal/genéticaRESUMO
Vasoproliferative retinal tumor (VPT) is a term proposed by ophthalmologists in relation to the totality of manifestations of an intraocular volumetric process with involvement of the inner lining of the eye, an integral part of which is the active growth of blood vessels. The available literature data on the morphology of this process are very contradictory and ambiguous. The article presents two clinical cases of vasoproliferative retinal tumor with own illustration of morphological studies.
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Retina , Neoplasias da Retina , Humanos , Retina/patologia , Neoplasias da Retina/genética , Neoplasias da Retina/patologiaRESUMO
The study aimed to assess the effect and mechanism of safflower injection in preventing retinal vein thrombosis in rabbits. Twenty healthy adult pigmented rabbits were randomly assigned to either the experimental group, receiving safflower injection, or the control group, receiving normal saline. After two weeks of treatment, blood samples were collected to analyze platelet adhesion and aggregation rates. Photodynamic therapy was applied to induce occlusion in the target retinal vein. Fundus photography and fluorescein angiography were recorded using a dynamic microscopic monitoring system, and laser speckle imaging was employed to assess blood flow in the affected vein. The experimental group exhibited significantly lower rates of platelet adhesion and aggregation compared to the control group. Following the induction of retinal vein occlusion, the experimental group showed a lower complete occlusion rate of the target retinal vein. Although initial blood flow in the target vein was similar between groups, the blood flow at 1, 3, and 5 min post-occlusion was significantly higher in the experimental group. Safflower injection delayed retinal vein thrombosis formation, preserved blood flow in the affected retinal area, and reduced platelet adhesion and aggregation. These effects facilitated vascular reperfusion within a limited timeframe.
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Carthamus tinctorius , Oclusão da Veia Retiniana , Veia Retiniana , Animais , Coelhos , Oclusão da Veia Retiniana/tratamento farmacológico , Modelos Animais de Doenças , Retina , AngiofluoresceinografiaRESUMO
BACKGROUND: Ageing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown. METHODS: Regulatory T cells were selectively depleted in both young (2-4 months) and aged (18-23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni's post hoc test. RESULTS: Our study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes. CONCLUSION: Our findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.