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1.
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
2.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732004

RESUMO

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.


Assuntos
Produtos Finais de Glicação Avançada , Degeneração Macular , Degeneração Macular/tratamento farmacológico , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Animais , Suínos , Retina/metabolismo , Retina/efeitos dos fármacos , Retina/patologia , Aminoácido Oxirredutases
3.
BMJ Case Rep ; 17(5)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719246

RESUMO

Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.


Assuntos
Livedo Reticular , Dermatopatias Vasculares , Telangiectasia , Humanos , Feminino , Telangiectasia/congênito , Telangiectasia/complicações , Telangiectasia/diagnóstico , Dermatopatias Vasculares/diagnóstico , Dermatopatias Vasculares/complicações , Lactente , Fotocoagulação a Laser/métodos , Vasos Retinianos/anormalidades , Vasos Retinianos/diagnóstico por imagem , Retina/anormalidades , Retina/diagnóstico por imagem
4.
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
5.
J Biomed Opt ; 29(6): 066002, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38745984

RESUMO

Significance: Optical coherence tomography (OCT) has emerged as the standard of care for diagnosing and monitoring the treatment of various ocular disorders due to its noninvasive nature and in vivo volumetric acquisition capability. Despite its widespread applications in ophthalmology, motion artifacts remain a challenge in OCT imaging, adversely impacting image quality. While several multivolume registration algorithms have been developed to address this issue, they are often designed to cater to one specific OCT system or acquisition protocol. Aim: We aim to generate an OCT volume free of motion artifacts using a system-agnostic registration algorithm that is independent of system specifications or protocol. Approach: We developed a B-scan registration algorithm that removes motion and corrects for both translational eye movements and rotational angle differences between volumes. Tests were carried out on various datasets obtained from two different types of custom-built OCT systems and one commercially available system to determine the reliability of the proposed algorithm. Additionally, different system specifications were used, with variations in axial resolution, lateral resolution, signal-to-noise ratio, and real-time motion tracking. The accuracy of this method has further been evaluated through mean squared error (MSE) and multiscale structural similarity index measure (MS-SSIM). Results: The results demonstrate improvements in the overall contrast of the images, facilitating detailed visualization of retinal vasculatures in both superficial and deep vasculature plexus. Finer features of the inner and outer retina, such as photoreceptors and other pathology-specific features, are discernible after multivolume registration and averaging. Quantitative analyses affirm that increasing the number of averaged registered volumes will decrease MSE and increase MS-SSIM as compared to the reference volume. Conclusions: The multivolume registered data obtained from this algorithm offers significantly improved visualization of the retinal microvascular network as well as retinal morphological features. Furthermore, we have validated that the versatility of our methodology extends beyond specific OCT modalities, thereby enhancing the clinical utility of OCT for the diagnosis and monitoring of ocular pathologies.


Assuntos
Algoritmos , Imageamento Tridimensional , Retina , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Artefatos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
6.
Opt Lett ; 49(10): 2817-2820, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748169

RESUMO

Alteration in the elastic properties of biological tissues may indicate changes in the structure and components. Acoustic radiation force optical coherence elastography (ARF-OCE) can assess the elastic properties of the ocular tissues non-invasively. However, coupling the ultrasound beam and the optical beam remains challenging. In this Letter, we proposed an OCE method incorporating homolateral parallel ARF excitation for measuring the elasticity of the ocular tissues. An acoustic-optic coupling unit was established to reflect the ultrasound beam while transmitting the light beam. The ARF excited the ocular tissue in the direction parallel to the light beam from the same side of the light beam. We demonstrated the method on the agar phantoms, the porcine cornea, and the porcine retina. The results show that the ARF-OCE method can measure the elasticity of the cornea and the retina, resulting in higher detection sensitivity and a more extensive scanning range.


Assuntos
Córnea , Técnicas de Imagem por Elasticidade , Imagens de Fantasmas , Tomografia de Coerência Óptica , Técnicas de Imagem por Elasticidade/métodos , Animais , Suínos , Córnea/diagnóstico por imagem , Córnea/fisiologia , Tomografia de Coerência Óptica/métodos , Elasticidade , Retina/diagnóstico por imagem , Retina/fisiologia
7.
Invest Ophthalmol Vis Sci ; 65(5): 16, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717425

RESUMO

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.


Assuntos
Envelhecimento , Cognição , Degeneração Macular , Retina , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Idoso , Feminino , Estudos Transversais , Envelhecimento/fisiologia , Idoso de 80 Anos ou mais , Degeneração Macular/fisiopatologia , Cognição/fisiologia , Retina/diagnóstico por imagem , Retina/patologia , Retina/fisiopatologia , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia
8.
Elife ; 122024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739438

RESUMO

The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised 1H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. This selective vulnerability of photoreceptors suggested very specific adaptations in their energy metabolism. Rod photoreceptors were found to rely strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were dependent on glycolysis but insensitive to electron transport chain decoupling. Importantly, photoreceptors appeared to uncouple glycolytic and Krebs-cycle metabolism via three different pathways: (1) the mini-Krebs-cycle, fuelled by glutamine and branched chain amino acids, generating N-acetylaspartate; (2) the alanine-generating Cahill-cycle; (3) the lactate-releasing Cori-cycle. Moreover, the metabolomics data indicated a shuttling of taurine and hypotaurine between the retinal pigment epithelium and photoreceptors, likely resulting in an additional net transfer of reducing power to photoreceptors. These findings expand our understanding of retinal physiology and pathology and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases.


Assuntos
Ciclo do Ácido Cítrico , Glicólise , Fosforilação Oxidativa , Retina , Animais , Camundongos , Retina/metabolismo , Metabolismo Energético , Metabolômica , Epitélio Pigmentado da Retina/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Camundongos Endogâmicos C57BL , Células Fotorreceptoras Retinianas Cones/metabolismo
10.
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
11.
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
12.
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
13.
Zhonghua Yan Ke Za Zhi ; 60(5): 451-453, 2024 May 11.
Artigo em Chinês | MEDLINE | ID: mdl-38706084

RESUMO

A 36-year-old male patient presented with a decrease in vision after undergoing scleral suturing for a left eye injury caused by an iron hook, combined with intravitreal injection of cefuroxime. Ocular examination revealed extensive gray-white edematous areas in the macular region, along with focal serous shallow retinal detachment in the posterior pole. Following admission, comprehensive ophthalmic examinations were conducted, leading to the diagnosis of toxic retinal damage in the left eye. Treatment with oral corticosteroids and interventions to improve microcirculation were initiated, resulting in improved visual acuity. At the six-month follow-up, the patient's visual acuity had recovered to 0.5.


Assuntos
Cefuroxima , Humanos , Masculino , Adulto , Cefuroxima/efeitos adversos , Cefuroxima/administração & dosagem , Injeções Intravítreas , Antibacterianos/efeitos adversos , Descolamento Retiniano , Retina
14.
Nat Commun ; 15(1): 3780, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710714

RESUMO

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Assuntos
Neovascularização de Coroide , Dependovirus , Terapia Genética , Vetores Genéticos , Epitélio Pigmentado da Retina , Animais , Dependovirus/genética , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Terapia Genética/métodos , Camundongos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/virologia , Neovascularização de Coroide/terapia , Neovascularização de Coroide/genética , Coelhos , Humanos , Técnicas de Transferência de Genes , Degeneração Macular/terapia , Degeneração Macular/genética , Degeneração Macular/patologia , Modelos Animais de Doenças , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Transdução Genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/virologia , Masculino , Células HEK293
15.
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
16.
Methods Mol Biol ; 2800: 67-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709478

RESUMO

The study of cell signaling within tissues can be enhanced using highly multiplexed immunohistochemistry to localize the presence and spatial distribution of numerous pathways of interest simultaneously. Additional data can also be gained by placing the identified proteins into the context of adjacent structures, stroma, and interacting partners. Here, we outline a protocol for using the recently described IBEX method on tissues. This is an open and simple cyclic immunohistochemistry approach suited to this application. We describe a simplified protocol and provide guidance on the method, using a 12-marker panel on human retina to demonstrate the approach.


Assuntos
Imuno-Histoquímica , Retina , Transdução de Sinais , Humanos , Imuno-Histoquímica/métodos , Retina/metabolismo , Retina/citologia , Biomarcadores , Imagem Molecular/métodos
17.
Mol Biol Rep ; 51(1): 606, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704498

RESUMO

BACKGROUND: Recent in vitro studies using RB1+/- fibroblasts and MSCs have shown molecular and functional disruptions without the need for biallelic loss of RB1. However, this was not reflected in the recent in vitro studies employing RB1+/- retinal organoids. To gain further insights into the molecular disruptions in the RB1+/- retinal organoids, we performed a high throughput RNA sequencing analysis. METHODS AND RESULTS: iPSCs were generated from RB1+/+ and RB1+/- OAMSCs derived from retinoblastoma patients. RB1+/+ and RB1+/- iPSCs were subjected to a step-wise retinal differentiation protocol. Retinal differentiation was evaluated by Real-time PCR and flow cytometry analysis of the retinal markers. To gain further insights into the molecular differences in RB1+/- retinal organoids, a high throughput RNA sequencing followed by differential gene expression analysis and gene set enrichment analysis (GSEA) was performed. The analysis revealed a shift from the regular metabolic process of glycolysis to oxidative phosphorylation in the RB1+/- retinal organoids. To investigate further, we performed assays to determine the levels of pyruvate, lactate and ATP in the retinal organoids. The results revealed significant increase in ATP and pyruvate levels in RB1+/- retinal organoids of day 120 compared to that of the RB1+/+. The results thus revealed enhanced ATP production in the RB1+/- retinal organoids. CONCLUSION: The study provides novel insights into the metabolic phenotype of heterozygous RB1 mutant suggesting dysregulation of energy metabolism and glycolytic pathways to be first step even before the changes in cellular proliferation or other phenotypic consequences ensue.


Assuntos
Trifosfato de Adenosina , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas , Mutação , Organoides , Retina , Retinoblastoma , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/citologia , Organoides/metabolismo , Retina/metabolismo , Retina/citologia , Retinoblastoma/genética , Retinoblastoma/metabolismo , Trifosfato de Adenosina/metabolismo , Diferenciação Celular/genética , Mutação/genética , Heterozigoto , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Glicólise/genética , Proteínas de Ligação a Retinoblastoma/genética , Proteínas de Ligação a Retinoblastoma/metabolismo
18.
PLoS One ; 19(5): e0300584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709779

RESUMO

Though rod and cone photoreceptors use similar phototransduction mechanisms, previous model calculations have indicated that the most important differences in their light responses are likely to be differences in amplification of the G-protein cascade, different decay rates of phosphodiesterase (PDE) and pigment phosphorylation, and different rates of turnover of cGMP in darkness. To test this hypothesis, we constructed TrUx;GapOx rods by crossing mice with decreased transduction gain from decreased transducin expression, with mice displaying an increased rate of PDE decay from increased expression of GTPase-activating proteins (GAPs). These two manipulations brought the sensitivity of TrUx;GapOx rods to within a factor of 2 of WT cone sensitivity, after correcting for outer-segment dimensions. These alterations did not, however, change photoreceptor adaptation: rods continued to show increment saturation though at a higher background intensity. These experiments confirm model calculations that rod responses can mimic some (though not all) of the features of cone responses after only a few changes in the properties of transduction proteins.


Assuntos
Células Fotorreceptoras Retinianas Cones , Células Fotorreceptoras Retinianas Bastonetes , Transducina , Animais , Células Fotorreceptoras Retinianas Cones/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Camundongos , Transducina/metabolismo , Transducina/genética , Retina/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Diester Fosfórico Hidrolases/genética
19.
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
20.
Sensors (Basel) ; 24(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38732784

RESUMO

Artificial retinas have revolutionized the lives of many blind people by enabling their ability to perceive vision via an implanted chip. Despite significant advancements, there are some limitations that cannot be ignored. Presenting all objects captured in a scene makes their identification difficult. Addressing this limitation is necessary because the artificial retina can utilize a very limited number of pixels to represent vision information. This problem in a multi-object scenario can be mitigated by enhancing images such that only the major objects are considered to be shown in vision. Although simple techniques like edge detection are used, they fall short in representing identifiable objects in complex scenarios, suggesting the idea of integrating primary object edges. To support this idea, the proposed classification model aims at identifying the primary objects based on a suggested set of selective features. The proposed classification model can then be equipped into the artificial retina system for filtering multiple primary objects to enhance vision. The suitability of handling multi-objects enables the system to cope with real-world complex scenarios. The proposed classification model is based on a multi-label deep neural network, specifically designed to leverage from the selective feature set. Initially, the enhanced images proposed in this research are compared with the ones that utilize an edge detection technique for single, dual, and multi-object images. These enhancements are also verified through an intensity profile analysis. Subsequently, the proposed classification model's performance is evaluated to show the significance of utilizing the suggested features. This includes evaluating the model's ability to correctly classify the top five, four, three, two, and one object(s), with respective accuracies of up to 84.8%, 85.2%, 86.8%, 91.8%, and 96.4%. Several comparisons such as training/validation loss and accuracies, precision, recall, specificity, and area under a curve indicate reliable results. Based on the overall evaluation of this study, it is concluded that using the suggested set of selective features not only improves the classification model's performance, but aligns with the specific problem to address the challenge of correctly identifying objects in multi-object scenarios. Therefore, the proposed classification model designed on the basis of selective features is considered to be a very useful tool in supporting the idea of optimizing image enhancement.


Assuntos
Inteligência Artificial , Redes Neurais de Computação , Retina , Retina/diagnóstico por imagem , Humanos , Aumento da Imagem/métodos , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Próteses Visuais
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