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1.
Sci Rep ; 14(1): 12790, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834830

RESUMO

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/- 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = - 0.2 and r = - 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.


Assuntos
Peso ao Nascer , Idade Gestacional , Retinopatia da Prematuridade , Humanos , Recém-Nascido , Feminino , Masculino , Estudos Prospectivos , Recém-Nascido Prematuro , Velocidade do Fluxo Sanguíneo , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiopatologia , Retina/fisiopatologia , Retina/diagnóstico por imagem , Fatores de Risco , Fluxo Sanguíneo Regional
2.
J. optom. (Internet) ; 17(2): [100502], Abr-Jun, 2024. graf
Artigo em Inglês | IBECS | ID: ibc-231625

RESUMO

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 (1–2 days) and after (2–3 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)


Assuntos
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 Visuais
3.
Zhonghua Yan Ke Za Zhi ; 60(6): 547-558, 2024 Jun 11.
Artigo em Chinês | MEDLINE | ID: mdl-38825955

RESUMO

With the increasing prevalence of myopia among adolescents, the pathogenesis of this condition has garnered significant attention. Studies have discovered the expression of various hormone receptors in ocular tissues of both animals and humans. Additionally, changes in hormone levels accompany the development of myopia, although the exact relationships remain inconclusive. This article reviews the potential influences and mechanisms of action of endogenous hormones such as melatonin, serotonin, insulin, glucagon, sex hormones, vitamin D, and prostaglandins in ocular tissues including the retina, choroid, and sclera. It elaborates on the relationship between fluctuations in these hormone levels and the progression of myopia, aiming to provide guidance for exploring targets for myopia prevention and control.


Assuntos
Melatonina , Miopia , Humanos , Miopia/metabolismo , Melatonina/metabolismo , Vitamina D/metabolismo , Serotonina/metabolismo , Insulina/metabolismo , Glucagon/metabolismo , Animais , Hormônios Esteroides Gonadais/metabolismo , Prostaglandinas/metabolismo , Hormônios/metabolismo , Retina/metabolismo
4.
Zhonghua Yan Ke Za Zhi ; 60(6): 541-546, 2024 Jun 11.
Artigo em Chinês | MEDLINE | ID: mdl-38825954

RESUMO

The increasing incidence of myopia has become a global public health concern. Exploring the mechanisms underlying the onset and progression of myopia is crucial for prevention and control. This paper reviews the role of peripheral retinal defocus mechanisms in the development of myopia, with particular emphasis on the interaction between accommodation lag and peripheral retinal defocus, as well as the impact of optical intervention on myopia control effectiveness. In recent years, researchers have developed various optical tools for myopia prevention and control based on the peripheral retinal defocus theory, such as peripheral defocus spectacle lenses, orthokeratology lenses, and peripheral defocus soft contact lenses. This paper aims to provide clinicians with the latest research findings to deepen their understanding of the mechanisms involved in myopia development and to guide the future development and clinical application of myopia prevention and control products.


Assuntos
Progressão da Doença , Miopia , Retina , Humanos , Miopia/terapia , Miopia/fisiopatologia , Acomodação Ocular , Óculos , Lentes de Contato Hidrofílicas , Procedimentos Ortoceratológicos/métodos , Refração Ocular
5.
Invest Ophthalmol Vis Sci ; 65(6): 12, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38842829

RESUMO

Purpose: To test the hypothesis that (C-C motif) ligand 2 (CCL2) and CCL3 impact retinal function decline and inflammation during Staphylococcus aureus endophthalmitis. Methods: Experimental endophthalmitis was initiated by intravitreal injection of 5000 colony-forming units of S. aureus into the eyes of C57BL/6J, CCL2-/-, or CCL3-/- mice. At 12 and 24 hours post-infection, retinal function, bacterial load, and myeloperoxidase levels were quantified. Results: During S. aureus endophthalmitis, we observed a significant improvement in retinal function in CCL2-/- mice relative to C57BL/6J mice at 12 hours but not at 24 hours. In CCL3-/- mice, retinal function was significantly improved relative to C57BL/6J mice at 12 and 24 hours. The absence of CCL2 did not alter intraocular S. aureus intraocular concentrations. However, CCL3-/- mice had significantly lower intraocular S. aureus at 12 hours but not at 24 hours. No difference in myeloperoxidase levels was observed between C57BL/6J and CCL2-/- mice at 12 hours. CCL3-/- mice had almost no myeloperoxidase at 12 hours. At 24 hours, increased myeloperoxidase was observed in CCL2-/- and CCL3-/- mice relative to C57BL/6J mice. Conclusions: Although the absence of CCL2 resulted in improved retinal function retention at 12 hours, CCL3 deficiency resulted in improved retinal function at 12 and 24 hours. CCL3 deficiency, but not CCL2 deficiency, resulted in almost no inflammation at 12 hours. However, at 24 hours, the absence of CCL2 or CCL3 resulted in significantly increased inflammation. These results suggest that, although both CCL2 and CCL3 impact intraocular infection outcomes, CCL3 may have a more significant impact in S. aureus endophthalmitis.


Assuntos
Quimiocina CCL2 , Quimiocina CCL3 , Modelos Animais de Doenças , Endoftalmite , Infecções Oculares Bacterianas , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Endoftalmite/microbiologia , Endoftalmite/metabolismo , Camundongos , Infecções Estafilocócicas/microbiologia , Infecções Oculares Bacterianas/microbiologia , Quimiocina CCL2/metabolismo , Quimiocina CCL3/metabolismo , Camundongos Knockout , Peroxidase/metabolismo , Retina/metabolismo , Retina/microbiologia , Eletrorretinografia
6.
Invest Ophthalmol Vis Sci ; 65(6): 10, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38842831

RESUMO

Purpose: To investigate whether fractal dimension (FD)-based oculomics could be used for individual risk prediction by evaluating repeatability and robustness. Methods: We used two datasets: "Caledonia," healthy adults imaged multiple times in quick succession for research (26 subjects, 39 eyes, 377 color fundus images), and GRAPE, glaucoma patients with baseline and follow-up visits (106 subjects, 196 eyes, 392 images). Mean follow-up time was 18.3 months in GRAPE; thus it provides a pessimistic lower bound because vasculature could change. FD was computed with DART and AutoMorph. Image quality was assessed with QuickQual, but no images were initially excluded. Pearson, Spearman, and intraclass correlation (ICC) were used for population-level repeatability. For individual-level repeatability, we introduce measurement noise parameter λ, which is within-eye standard deviation (SD) of FD measurements in units of between-eyes SD. Results: In Caledonia, ICC was 0.8153 for DART and 0.5779 for AutoMorph, Pearson/Spearman correlation (first and last image) 0.7857/0.7824 for DART, and 0.3933/0.6253 for AutoMorph. In GRAPE, Pearson/Spearman correlation (first and next visit) was 0.7479/0.7474 for DART, and 0.7109/0.7208 for AutoMorph (all P < 0.0001). Median λ in Caledonia without exclusions was 3.55% for DART and 12.65% for AutoMorph and improved to up to 1.67% and 6.64% with quality-based exclusions, respectively. Quality exclusions primarily mitigated large outliers. Worst quality in an eye correlated strongly with λ (Pearson 0.5350-0.7550, depending on dataset and method, all P < 0.0001). Conclusions: Repeatability was sufficient for individual-level predictions in heterogeneous populations. DART performed better on all metrics and might be able to detect small, longitudinal changes, highlighting the potential of robust methods.


Assuntos
Fractais , Humanos , Feminino , Reprodutibilidade dos Testes , Masculino , Pessoa de Meia-Idade , Adulto , Medição de Risco/métodos , Idoso , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Seguimentos , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem
7.
Nat Commun ; 15(1): 4829, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844438

RESUMO

Orientation or axial selectivity, the property of neurons in the visual system to respond preferentially to certain angles of visual stimuli, plays a pivotal role in our understanding of visual perception and information processing. This computation is performed as early as the retina, and although much work has established the cellular mechanisms of retinal orientation selectivity, how this computation is organized across the retina is unknown. Using a large dataset collected across the mouse retina, we demonstrate functional organization rules of retinal orientation selectivity. First, we identify three major functional classes of retinal cells that are orientation selective and match previous descriptions. Second, we show that one orientation is predominantly represented in the retina and that this predominant orientation changes as a function of retinal location. Third, we demonstrate that neural activity plays little role on the organization of retinal orientation selectivity. Lastly, we use in silico modeling followed by validation experiments to demonstrate that the overrepresented orientation aligns along concentric axes. These results demonstrate that, similar to direction selectivity, orientation selectivity is organized in a functional map as early as the retina.


Assuntos
Orientação , Retina , Animais , Retina/fisiologia , Camundongos , Orientação/fisiologia , Estimulação Luminosa , Camundongos Endogâmicos C57BL , Simulação por Computador , Percepção Visual/fisiologia , Modelos Neurológicos , Orientação Espacial/fisiologia , Células Ganglionares da Retina/fisiologia
8.
Acta Neuropathol Commun ; 12(1): 89, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845058

RESUMO

The microtubule-associated protein Tau is a key player in various neurodegenerative conditions, including Alzheimer's disease (AD) and Tauopathies, where its hyperphosphorylation disrupts neuronal microtubular lattice stability. Glaucoma, a neurodegenerative disorder affecting the retina, leads to irreversible vision loss by damaging retinal ganglion cells and the optic nerve, often associated with increased intraocular pressure. Prior studies have indicated Tau expression and phosphorylation alterations in the retina in both AD and glaucoma, yet the causative or downstream nature of Tau protein changes in these pathologies remains unclear. This study investigates the impact of Tau protein modulation on retinal neurons under normal and experimental glaucoma conditions. Employing AAV9-mediated gene therapy for Tau overexpression and knockdown, both manipulations were found to adversely affect retinal structural and functional measures as well as neuroprotective Akt/Erk survival signalling in healthy conditions. In the experimental glaucoma model, Tau overexpression intensified inner retinal degeneration, while Tau silencing provided significant protection against these degenerative changes. These findings underscore the critical role of endogenous Tau protein levels in preserving retinal integrity and emphasize the therapeutic potential of targeting Tau in glaucoma pathology.


Assuntos
Terapia Genética , Glaucoma , Proteínas tau , Proteínas tau/metabolismo , Animais , Glaucoma/metabolismo , Glaucoma/patologia , Glaucoma/genética , Terapia Genética/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Dependovirus/genética , Modelos Animais de Doenças , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Degeneração Retiniana/genética , Retina/metabolismo , Retina/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Transdução de Sinais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Fenótipo
9.
PLoS One ; 19(6): e0304943, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38837967

RESUMO

Age-related macular degeneration (AMD) is an eye disease that leads to the deterioration of the central vision area of the eye and can gradually result in vision loss in elderly individuals. Early identification of this disease can significantly impact patient treatment outcomes. Furthermore, given the increasing elderly population globally, the importance of automated methods for rapidly monitoring at-risk individuals and accurately diagnosing AMD is growing daily. One standard method for diagnosing AMD is using optical coherence tomography (OCT) images as a non-invasive imaging technology. In recent years, numerous deep neural networks have been proposed for the classification of OCT images. Utilizing pre-trained neural networks can speed up model deployment in related tasks without compromising accuracy. However, most previous methods overlook the feasibility of leveraging pre-existing trained networks to search for an optimal architecture for AMD staging on a new target dataset. In this study, our objective was to achieve an optimal architecture in the efficiency-accuracy trade-off for classifying retinal OCT images. To this end, we employed pre-trained medical vision transformer (MedViT) models. MedViT combines convolutional and transformer neural networks, explicitly designed for medical image classification. Our approach involved pre-training two distinct MedViT models on a source dataset with labels identical to those in the target dataset. This pre-training was conducted in a supervised manner. Subsequently, we evaluated the performance of the pre-trained MedViT models for classifying retinal OCT images from the target Noor Eye Hospital (NEH) dataset into the normal, drusen, and choroidal neovascularization (CNV) classes in zero-shot settings and through five-fold cross-validation. Then, we proposed a stitching approach to search for an optimal model from two MedViT family models. The proposed stitching method is an efficient architecture search algorithm known as stitchable neural networks. Stitchable neural networks create a candidate model in search space for each pair of stitchable layers by inserting a linear layer between them. A pair of stitchable layers consists of layers, each selected from one input model. While stitchable neural networks had previously been tested on more extensive and general datasets, this study demonstrated that stitching networks could also be helpful in smaller medical datasets. The results of this approach indicate that when pre-trained models were available for OCT images from another dataset, it was possible to achieve a model in 100 epochs with an accuracy of over 94.9% in classifying images from the NEH dataset. The results of this study demonstrate the efficacy of stitchable neural networks as a fine-tuning method for OCT image classification. This approach not only leads to higher accuracy but also considers architecture optimization at a reasonable computational cost.


Assuntos
Degeneração Macular , Redes Neurais de Computação , Retina , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Degeneração Macular/diagnóstico por imagem , Retina/diagnóstico por imagem , Retina/patologia , Idoso , Algoritmos
10.
J Neuroinflammation ; 21(1): 145, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824526

RESUMO

BACKGROUND: Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL. METHODS: Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia. RESULTS: Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products. CONCLUSIONS: A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.


Assuntos
Astrócitos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD , Glaucoma , Doenças Neuroinflamatórias , Animais , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Camundongos , Astrócitos/metabolismo , Astrócitos/patologia , Glaucoma/metabolismo , Glaucoma/patologia , Glaucoma/genética , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Camundongos Transgênicos , Modelos Animais de Doenças , Citocinas/metabolismo , Retina/metabolismo , Retina/patologia , Camundongos Endogâmicos C57BL , Nervo Óptico/patologia , Nervo Óptico/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo
11.
Invest Ophthalmol Vis Sci ; 65(6): 3, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829669

RESUMO

Purpose: Investigating influencing factors on the pupillary light response (PLR) as a biomarker for local retinal function by providing epidemiological data of a large normative collective and to establish a normative database for the evaluation of chromatic pupil campimetry (CPC). Methods: Demographic and ophthalmologic characteristics were captured and PLR parameters of 150 healthy participants (94 women) aged 18 to 79 years (median = 46 years) were measured with L-cone- and rod-favoring CPC protocols. Linear-mixed effects models were performed to determine factors influencing the PLR and optical coherence tomography (OCT) data were correlated with the pupillary function volume. Results: Relative maximal constriction amplitude (relMCA) and latency under L-cone- and rod-favoring stimulation were statistically significantly affected by the stimulus eccentricity (P < 0.0001, respectively). Iris color and gender did not affect relMCA or latency significantly; visual hemifield, season, and daytime showed only minor influence under few stimulus conditions. Age had a statistically significant effect on latency under rod-specific stimulation with a latency prolongation ≥60 years. Under photopic and scotopic conditions, baseline pupil diameter declined significantly with increasing age (P < 0.0001, respectively). Pupillary function volume and OCT data were not correlated relevantly. Conclusions: Stimulus eccentricity had the most relevant impact on relMCA and latency of the PLR during L-cone- and rod-favoring stimulation. Latency is prolonged ≥60 years under scotopic conditions. Considering the large study collective, a representative normative database for relMCA and latency as valid readout parameters for L-cone- and rod-favoring stimulation could be established. This further validates the usability of the PLR in CPC as a biomarker for local retinal function.


Assuntos
Pupila , Reflexo Pupilar , Tomografia de Coerência Óptica , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Adulto Jovem , Tomografia de Coerência Óptica/métodos , Pupila/fisiologia , Adolescente , Reflexo Pupilar/fisiologia , Biomarcadores , Estimulação Luminosa , Retina/fisiologia , Retina/diagnóstico por imagem , Voluntários Saudáveis , Luz , Valores de Referência
12.
Sci Rep ; 14(1): 12718, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830921

RESUMO

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.


Assuntos
Corioide , Melatonina , Microvasos , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Masculino , Adulto , Feminino , Melatonina/urina , Melatonina/análogos & derivados , Microvasos/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Pessoa de Meia-Idade , Jornada de Trabalho em Turnos/efeitos adversos , Angiografia/métodos , Retina/diagnóstico por imagem
13.
J Vis ; 24(6): 2, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38833255

RESUMO

The spectral locus of unique yellow was determined for flashes of different sizes (<11 arcmin) and durations (<500 ms) presented in and near the fovea. An adaptive optics scanning laser ophthalmoscope was used to minimize the effects of higher-order aberrations during simultaneous stimulus delivery and retinal imaging. In certain subjects, parafoveal cones were classified as L, M, or S, which permitted the comparison of unique yellow measurements with variations in local L/M ratios within and between observers. Unique yellow shifted to longer wavelengths as stimulus size or duration was reduced. This effect is most pronounced for changes in size and more apparent in the fovea than in the parafovea. The observed variations in unique yellow are not entirely predicted from variations in L/M ratio and therefore implicate neural processes beyond photoreception.


Assuntos
Fóvea Central , Estimulação Luminosa , Células Fotorreceptoras Retinianas Cones , Humanos , Estimulação Luminosa/métodos , Células Fotorreceptoras Retinianas Cones/fisiologia , Fóvea Central/fisiologia , Percepção de Cores/fisiologia , Retina/fisiologia , Adulto , Oftalmoscopia/métodos
14.
Nat Commun ; 15(1): 4756, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834544

RESUMO

Given the absence of approved treatments for pathogenic variants in Peripherin-2 (PRPH2), it is imperative to identify a universally effective therapeutic target for PRPH2 pathogenic variants. To test the hypothesis that formation of the elongated discs in presence of PRPH2 pathogenic variants is due to the presence of the full complement of rhodopsin in absence of the required amounts of functional PRPH2. Here we demonstrate the therapeutic potential of reducing rhodopsin levels in ameliorating disease phenotype in knockin models for p.Lys154del (c.458-460del) and p.Tyr141Cys (c.422 A > G) in PRPH2. Reducing rhodopsin levels improves physiological function, mitigates the severity of disc abnormalities, and decreases retinal gliosis. Additionally, intravitreal injections of a rhodopsin-specific antisense oligonucleotide successfully enhance the physiological function of photoreceptors and improves the ultrastructure of discs in mutant mice. Presented findings shows that reducing rhodopsin levels is an effective therapeutic strategy for the treatment of inherited retinal degeneration associated with PRPH2 pathogenic variants.


Assuntos
Periferinas , Rodopsina , Periferinas/genética , Periferinas/metabolismo , Animais , Rodopsina/genética , Rodopsina/metabolismo , Camundongos , Humanos , Modelos Animais de Doenças , Regulação para Baixo , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Degeneração Retiniana/terapia , Oligonucleotídeos Antissenso/genética , Retina/metabolismo , Retina/patologia , Doenças Retinianas/genética , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Doenças Retinianas/terapia , Camundongos Endogâmicos C57BL , Mutação , Feminino , Técnicas de Introdução de Genes , Masculino
15.
Invest Ophthalmol Vis Sci ; 65(5): 5, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38696189

RESUMO

Purpose: Neuroinflammation plays a significant role in the pathology of Alzheimer's disease (AD). Mouse models of AD and postmortem biopsy of patients with AD reveal retinal glial activation comparable to central nervous system immunoreactivity. We hypothesized that the surface area of putative retinal gliosis observed in vivo using en face optical coherence tomography (OCT) imaging will be larger in patients with preclinical AD versus controls. Methods: The Spectralis II instrument was used to acquire macular centered 20 × 20 and 30 × 25-degrees spectral domain OCT images of 76 participants (132 eyes). A cohort of 22 patients with preclinical AD (40 eyes, mean age = 69 years, range = 60-80 years) and 20 control participants (32 eyes, mean age = 66 years, range = 58-82 years, P = 0.11) were included for the assessment of difference in surface area of putative retinal gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map were compared between groups using generalized linear mixed models. Results: The surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1,70) = 4.41, P = 0.039; Cohen's d = 0.61. There was no significant difference between groups for RNFL thickness in the 9 ETDRS sectors, P > 0.05. Conclusions: Our analysis shows greater putative retinal gliosis in preclinical AD compared to controls. This demonstrates putative retinal gliosis as a potential biomarker for AD-related neuroinflammation.


Assuntos
Doença de Alzheimer , Gliose , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Gliose/patologia , Gliose/diagnóstico , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Feminino , Masculino , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Fibras Nervosas/patologia , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Retina/patologia , Retina/diagnóstico por imagem
16.
BMC Biol ; 22(1): 106, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715001

RESUMO

BACKGROUND: The significance of A-to-I RNA editing in nervous system development is widely recognized; however, its influence on retina development remains to be thoroughly understood. RESULTS: In this study, we performed RNA sequencing and ribosome profiling experiments on developing mouse retinas to characterize the temporal landscape of A-to-I editing. Our findings revealed temporal changes in A-to-I editing, with distinct editing patterns observed across different developmental stages. Further analysis showed the interplay between A-to-I editing and alternative splicing, with A-to-I editing influencing splicing efficiency and the quantity of splicing events. A-to-I editing held the potential to enhance translation diversity, but this came at the expense of reduced translational efficiency. When coupled with splicing, it could produce a coordinated effect on gene translation. CONCLUSIONS: Overall, this study presents a temporally resolved atlas of A-to-I editing, connecting its changes with the impact on alternative splicing and gene translation in retina development.


Assuntos
Biossíntese de Proteínas , Edição de RNA , Retina , Animais , Camundongos , Retina/metabolismo , Retina/embriologia , Processamento Alternativo , Inosina/metabolismo , Inosina/genética , Adenosina/metabolismo
17.
BMC Ophthalmol ; 24(1): 208, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715011

RESUMO

BACKGROUND: To find the relationship between the changes of retinal and choriodal structure/ vascular densities (VD) and the myopia progress. METHODS: 126 eyes of 126 age-matched young participants were divided into three groups: Emmetropia and Low Myopia (EaLM) (33 eyes), Moderate Myopia (MM) (39 eyes), and High Myopia (HM) (54 eyes). Fundus images measuring 12 × 12 mm were captured using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Each image was uniformly divided into nine regions: supra-temporal (ST), temporal (T), infra-temporal (IT), superior (S), central macular area (C), inferior (I), supra-nasal (SN), nasal (N), and infra-nasal (IN). Various structural parameters, including inner retina thickness (IRT), outer retina thickness (ORT), and choroid thickness (CT), were assessed, and the VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaries (CC), and choroid vessels (ChdV) were quantified. RESULTS: CT in upper fundus exhibited a significant reduction from EaLM to MM. Additionally, ORT (ST, S. SN, C, N, IT, I, IN), CT (ST, S, SN, T, C, N, IT, I, IN) and VDs of SCP (ST, S, C, I, IN), DCP (ST, S, T, C, I) and ChdV (T, N, I, IN) were statistically diminished in EaLM compared to HM. Furthermore, IRT (N), ORT (N, IN), CT (S, SN, T, C, IT, I) and VDs of SCP (I, IN) and DCP (I) exhibited significant decreases as MM progressed towards HM. Intriguingly, there was a notable increase in the VD of CC (ST, S, T, C, N) as myopia progressed from MM to HM. CONCLUSION: Significant changes in retinal and choroid structure and vascular density occur as moderate myopia advances to high myopia. Efforts to curb myopia progression to this stage are essential, as the failure to do so may lead to the development of corresponding retinopathy.


Assuntos
Corioide , Angiofluoresceinografia , Miopia , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/patologia , Masculino , Feminino , Adulto Jovem , Miopia/fisiopatologia , Adulto , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Angiofluoresceinografia/métodos , Retina/diagnóstico por imagem , Retina/patologia , Progressão da Doença , Adolescente , Fundo de Olho
18.
Opt Lett ; 49(9): 2209-2212, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691681

RESUMO

Under spatially incoherent illumination, time-domain full-field optical coherence tomography (FFOCT) offers the possibility to achieve in vivo retinal imaging at cellular resolution over a wide field of view. Such performance is possible, albeit there is the presence of ocular aberrations even without the use of classical adaptive optics. While the effect of aberrations in FFOCT has been debated these past years, mostly on low-order and static aberrations, we present, for the first time to our knowledge, a method enabling a quantitative study of the effect of statistically representative static and dynamic ocular aberrations on FFOCT image metrics, such as SNR, resolution, and image similarity. While we show that ocular aberrations can decrease FFOCT SNR and resolution by up to 14 dB and fivefold, we take advantage of such quantification to discuss different possible compromises between performance gain and adaptive optics complexity and speed, to optimize both sensor-based and sensorless FFOCT high-resolution retinal imaging.


Assuntos
Retina , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Humanos , Razão Sinal-Ruído
19.
Opt Lett ; 49(9): 2489-2492, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691751

RESUMO

Point scanning retinal imaging modalities, including confocal scanning light ophthalmoscopy (cSLO) and optical coherence tomography, suffer from fixational motion artifacts. Fixation targets, though effective at reducing eye motion, are infeasible in some applications (e.g., handheld devices) due to their bulk and complexity. Here, we report on a cSLO device that scans the retina in a spiral pattern under pseudo-visible illumination, thus collecting image data while simultaneously projecting, into the subject's vision, the image of a bullseye, which acts as a virtual fixation target. An imaging study of 14 young adult volunteers was conducted to compare the fixational performance of this technique to that of raster scanning, with and without a discrete inline fixation target. Image registration was used to quantify subject eye motion; a strip-wise registration method was used for raster scans, and a novel, to the best of our knowledge, ring-based method was used for spiral scans. Results indicate a statistically significant reduction in eye motion by the use of spiral scanning as compared to raster scanning without a fixation target.


Assuntos
Fixação Ocular , Oftalmoscopia , Retina , Humanos , Retina/diagnóstico por imagem , Fixação Ocular/fisiologia , Oftalmoscopia/métodos , Adulto , Adulto Jovem , Movimentos Oculares
20.
PLoS One ; 19(5): e0300621, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696393

RESUMO

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.


Assuntos
COVID-19 , Fibras Nervosas , Células Ganglionares da Retina , Humanos , COVID-19/patologia , COVID-19/complicações , Masculino , Decúbito Ventral , Feminino , Pessoa de Meia-Idade , Células Ganglionares da Retina/patologia , Estudos de Casos e Controles , Fibras Nervosas/patologia , Estudos Prospectivos , SARS-CoV-2 , Adulto , Idoso , Tomografia de Coerência Óptica , Retina/patologia , Estudos Longitudinais
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