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1.
Vision Res ; 220: 108388, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38593635

RESUMO

The function of exosomal miRNAs (miRs) in retinal degeneration is largely unclear. We were aimed to investigate the functions of exosomes as well as their miRs derived from retinal pigment epithelial (RPE) cells following exposure to oxidative stress (OS). After the OS by lipopolysaccharide and rotenone on RPE cells, interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) were upregulated, along with the decreased mitochondrial membrane potential and upregulated oxidative damage marker 8-OH-dG in RPE cells. RPE-derived exosomes were then isolated, identified, injected into the subretinal space in mice. After subretinal injection, RPE-exosomes after OS not only induced higher ROS level and apoptotic retinal cells, but also elevated IL-1ß, IL-6 alongside TNF-α expressions among retina/RPE/choroidal complex. Next, miRs inside the exosomes were sequenced by the next generation sequencing (NGS) technology. NGS revealed that certain miRs were abundant in exosomes, while others were selectively kept by RPE cells. Further, downregulated miRs, like miR-125b-5p, miR-125a-5p, alongside miR-128-3p, and upregulated miR, such as miR-7-5p were validated byRT-qPCR. Finally, Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to find the possible target genes of those selective exosomal miRs. Our results proved that the RPE-derived exosomes after OS selectively express certain miRs, providing novel insights into the pathogenesis of age-related macular degeneration (AMD) in future.


Assuntos
Exossomos , MicroRNAs , Estresse Oxidativo , Epitélio Pigmentado da Retina , Exossomos/metabolismo , MicroRNAs/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Estresse Oxidativo/fisiologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Apoptose , Regulação da Expressão Gênica/fisiologia , Humanos , Espécies Reativas de Oxigênio/metabolismo
2.
Exp Eye Res ; 243: 109912, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670210

RESUMO

Diabetic retinopathy (DR), a most common microangiopathy of diabetes, causes vision loss and even blindness. The mechanisms of exosomal lncRNA remain unclear in the development of DR. Here, we first identifed the pro-angiogenic effect of exosomes derived from vitreous humor of proliferative diabetic retinopathy patients, where lncRNA-MIAT was enriched inside. Secondly, lncRNA-MIAT was demonstrated significantly increased in exosomes from high glucose induced human retinal vascular endothelial cell, and can regulate tube formation, migration and proliferation ability to promote angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of lncRNA-MIAT was via the lncRNA-MIAT/miR-133a-3p/MMP-X1 axis. The reduced level of lncRNA-MIAT in this axis mitigated the generation of retinal neovascular in mouse model of oxygen-induced retinopathy (OIR), providing crucial evidence for lncRNA-MIAT as a potential clinical target. These findings enhance our understanding of the role of exosomal lncRNA-MIAT in retinal angiogenesis, and propose a promising therapeutic strategy against diabetic retinopathy.


Assuntos
Retinopatia Diabética , Exossomos , MicroRNAs , RNA Longo não Codificante , Neovascularização Retiniana , Retinopatia Diabética/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , RNA Longo não Codificante/genética , Animais , Exossomos/metabolismo , Exossomos/genética , Humanos , MicroRNAs/genética , Camundongos , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Camundongos Endogâmicos C57BL , Proliferação de Células , Masculino , Diabetes Mellitus Experimental , Movimento Celular , Células Cultivadas , Vasos Retinianos/metabolismo , Vasos Retinianos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica
3.
Nat Commun ; 15(1): 3588, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678013

RESUMO

Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users' eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of <0.5°, which is even less than the vision range of central fovea. Multiple eye-machine interaction applications, such as eye-drawing, Gluttonous Snake game, web interaction, pan-tilt-zoom camera control, and robot vehicle control, are demonstrated on the eye movement model and in vivo rabbit. Furthermore, comprehensive biocompatibility tests are implemented, demonstrating low cytotoxicity and low eye irritation. Thus, the contact lens is expected to enrich approaches of eye tracking techniques and promote the development of human-machine interaction technology.


Assuntos
Algoritmos , Lentes de Contato , Movimentos Oculares , Tecnologia de Rastreamento Ocular , Movimentos Oculares/fisiologia , Animais , Humanos , Coelhos , Sistemas Homem-Máquina
4.
J Nanobiotechnology ; 22(1): 56, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336783

RESUMO

Diabetic retinopathy (DR) is a vision-threatening diabetic complication that is characterized by microvasculature impairment and immune dysfunction. The present study demonstrated that M2 microglia intensively participated in retinal microangiopathy in human diabetic proliferative membranes, mice retinas, retinas of mice with oxygen-induced retinopathy (OIR) mice, and retinas of streptozotocin-induced DR mice. Further in vivo and in vitro experiments showed that exosomes derived from M2 polarized microglia (M2-exo) could reduce pericyte apoptosis and promote endothelial cell proliferation, thereby promoting vascular remodeling and reducing vascular leakage from the diabetic retina. These effects were further enhanced by M2-exo that facilitated M2 polarization of retinal microglia. Collectively, the study demonstrated the capability of M2-exo to induce retinal microvascular remodeling, which may provide a new therapeutic strategy for the treatment of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Exossomos , Camundongos , Animais , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Remodelação Vascular , Microglia , Retina
5.
Exp Eye Res ; 241: 109837, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382576

RESUMO

The lens is an avascular tissue, where epithelial cells (LECs) are the primary living cells. The role of LECs-derived exosomes (LEC-exos) is largely unknown. In our study, we determined the anti-angiogenic role of LEC-exos, manifested as regressed retinal neovascularization (NV) using the oxygen-induced retinopathy (OIR), and reduced choroidal NV size and pathological vascular leakage using the laser-induced choroidal neovascularization (laser-induced CNV). Furthermore, the activation and accumulation of microglia were also restricted by LEC-exos. Based on Luminex multiplex assays, the expressions of chemokines such as SCYB16/CXCL16, MCP-1/CCL2, I-TAC/CXCL11, and MIP 3beta/CCL19 were decreased after treatment with LEC-exos. Transwell assays showed that LEC-exos restricted the migration of the mouse microglia cell line (BV2 cells). After incubation with LEC-exos-treated BV2 cells, human umbilical vein endothelial cells (hUVECs) were collected for further evaluation using tube formation, Transwell assays, and 5-ethynyl-2'-deoxyuridine (EDU) assays. Using in vitro experiments, the pro-angiogenic effect of microglia was restricted by LEC-exos. Hence, it was investigated that LEC-exos attenuated ocular NV, which might attribute to the inhibition of microglial activation and accumulation.


Assuntos
Neovascularização de Coroide , Exossomos , Células-Tronco Mesenquimais , Camundongos , Animais , Humanos , Microglia , Exossomos/metabolismo , Angiogênese , Neovascularização Fisiológica/fisiologia , Células Endoteliais da Veia Umbilical Humana , Neovascularização de Coroide/metabolismo
6.
Int J Biol Sci ; 20(3): 897-915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38250154

RESUMO

Ocular angiogenic diseases, such as proliferative diabetic retinopathy (PDR), are often characterized by pathological new vessels and fibrosis formation. Anti-vascular endothelial growth factor (VEGF) therapy, despite of its efficiency to inhibit new vessels, has limitations, including drug resistance and retinal fibrosis. Here, we identified that Gremlin1, a novel angiogenesis and fibrosis inducer, was secreted from Müller glial cells, and its expression increased in the vitreous fluid from patients with PDR. Mechanistically, Gremlin1 triggered angiogenesis by promoting endothelial-mesenchymal transition via the EGFR/RhoA/ROCK pathway. In addition, Gremlin1 activated microglia to present profibrotic and fibrogenic properties. Further, anti-Gremlin1 antibody inhibited ocular angiogenesis and microglia fibrosis in mouse models. Collectively, Gremlin1 could be a potential therapeutic target in the treatment of ocular angiogenic diseases.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Peptídeos e Proteínas de Sinalização Intercelular , Animais , Humanos , Camundongos , Transporte Biológico , Retinopatia Diabética/tratamento farmacológico , Modelos Animais de Doenças , Olho , Fibrose , Peptídeos e Proteínas de Sinalização Intercelular/genética
7.
J Ophthalmol ; 2023: 1609332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37868692

RESUMO

Objective: This study aimed to evaluate conjunctival vessels in patients with dry eye disease (DED) using optical coherence tomography angiography (OCTA). Methods: This was a cross-sectional, observational clinical study. Twenty-three eyes of 18 patients with DED and 28 eyes of 23 healthy controls were included for examination in this study. The evaluation included the application of an Ocular Surface Disease Index Questionnaire, Schirmer Basic Secretion Test, and anterior OCTA targeting the temporal conjunctiva. AngioTool software was used to quantify the total vessel length and vessel density in the 3 × 3 mm temporal region of interest. Results: Blood vessel density measurements were compared across the OCTA systems. The total vessel length within the conjunctiva of the DED group (4799.34 ± 834.36) exceeded that of the control eye (3864.89 ± 1455.70) group (P < 0.05). However, the difference in vessel density between the two groups was not statistically significant. Conclusion: Measurement and analysis of conjunctival blood vessels using OCTA exhibited robust repeatability. In dry eyes, the total number of conjunctival blood vessels increased in accordance with disease severity. Hypoxia of conjunctival tissue may be an important cause of dry eye disease.

8.
FASEB J ; 37(10): e23192, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37682530

RESUMO

Abnormal ocular neovascularization, a major pathology of eye diseases, leads to severe visual loss. The role of lens epithelial cell (LEC)-derived exosomes (Lec-exo) is largely unknown. Thus, we aimed to investigate whether Lec-exo can inhibit abnormal ocular neovascularization and explore the possible mechanisms. In our study, we proved the first evidence that exosomes derived from LECs attenuated angiogenesis in both oxygen-induced retinopathy and laser-induced choroidal neovascularization mice models. Further in vitro experiments proved that Lec-exo inhibited proliferation, migration, and tube formation capability of human umbilical vein endothelial cells in high glucose condition. Further high-throughput miRNAs sequencing analysis detected that miR-146a-5p was enriched in Lec-exo. Mechanistically, exosomal miR-146a-5p was delivered to endothelial cells and bound to the NRAS coding sequence, which subsequently inactivated AKT/ERK signaling pathway. We successfully elucidated the function of Lec-exo in inhibiting abnormal ocular neovascularization, which may offer a promising strategy for treatment of abnormal ocular neovascularization.


Assuntos
Neovascularização de Coroide , Exossomos , MicroRNAs , Humanos , Animais , Camundongos , Células Epiteliais , Neovascularização de Coroide/genética , Células Endoteliais da Veia Umbilical Humana , MicroRNAs/genética
9.
Diabetes ; 72(9): 1307-1319, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37347724

RESUMO

Diabetic retinopathy (DR), one of the most common microangiopathic complications in diabetes, causes severe visual damage among working-age populations. Retinal vascular endothelial cells, the key cell type in DR pathogenesis, are responsible for abnormal retinal angiogenesis in advanced stages of DR. The roles of exosomes in DR have been largely unknown. In this study, we report the first evidence that exosomes derived from the vitreous humor of patients with proliferative DR (PDR-exo) promote proliferation, migration, and tube formation of human retinal vascular endothelial cells (HRVECs). We identified long noncoding RNA (lncRNA) LOC100132249 enrichment in PDR-exo via high-throughput sequencing. This lncRNA, also mainly derived from HRVECs, promoted angiogenesis both in vitro and in vivo. Mechanistically, LOC100132249 acted as a competing endogenous sponge of miRNA-199a-5p (miR-199a-5p), thus regulating the endothelial-mesenchymal transition promoter SNAI1 via activation of the Wnt/ß-catenin pathway and ultimately resulting in endothelial dysfunction. In conclusion, our findings underscored the pathogenic role of endothelial-derived exosomes via the LOC100132249/miR-199a-5p/SNAI1 axis in DR angiogenesis and may shed light on new therapeutic strategies for future treatment of DR. ARTICLE HIGHLIGHTS: This study provides the first evidence that exosomes derived from vitreous humor from patients with proliferative diabetic retinopathy participate in angiogenesis. The findings demonstrate an unreported long noncoding RNA (lncRNA), LOC100132249, by exosomal sequencing of vitreous humor. The newly found lncRNA LOC100132249, mainly derived from endothelial cells, promotes angiogenesis via an miRNA-199a-5p/SNAI1/Wnt/ß-catenin axis in a pro-endothelial-mesenchymal transition manner.


Assuntos
Retinopatia Diabética , Exossomos , MicroRNAs , RNA Longo não Codificante , Humanos , beta Catenina/metabolismo , Proliferação de Células/genética , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Exossomos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
10.
Comput Methods Programs Biomed ; 229: 107306, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36580822

RESUMO

BACKGROUND AND OBJECTIVE: Fundus fluorescein angiography (FFA) is widely used in clinical ophthalmic diagnosis and treatment with the requirement of adverse fluorescent dyes injection. Recently, many deep Convolutional Neural Network(CNN)-based methods have been proposed to estimate FFA from color fundus (CF) images to eliminate the use of adverse fluorescent dyes. However, the robustness of these methods is affected by pathological changes. METHOD: In this work, we present a CNN-based approach, lesion-aware generative adversarial networks (LA-GAN), to enhance the visual effect of lesion characteristics in the generated FFA images. First, we lead the generator notice lesion information by joint learning with lesion region segmentation. A new hierarchical correlation multi-task framework for high-resolution images is designed. Second, to enhance the visual contrast between normal regions and lesion regions, a newly designed region-level adversarial loss is used rather than the image-level adversarial loss. The code is publicly available at: https://github.com/nicetomeetu21/LA-GAN. RESULTS: The effectiveness of LA-Net has been verified in data with branch retinal vein occlusion. The proposed model reported as measures of generation performance a mean structural similarity (SSIM) of 0.536, mean learned perceptual image patch similarity (LPIPS) 0.312, outperforming other FFA generation and general image generation methods. Further, due to the proposed multi-task learning framework, the lesion-region segmentation performance was further reported as the mean Dice increased from 0.714 to 0.797 and the mean accuracy increased from 0.873 to 0.905, outperforming general single-task image segmentation methods. CONCLUSIONS: The results show that the visual effect of lesion characteristics can be improved by employing the region-level adversarial loss and the hierarchical correlation multi-task framework respectively. Based on the results of comparison with the state-of-the-art methods, LA-GAN is not only effective for CF-to-FFA translation, but also effective for lesion-region segmentation. Thus, it may be used for various image translation and lesion segmentation tasks in future research.


Assuntos
Corantes Fluorescentes , Processamento de Imagem Assistida por Computador , Angiofluoresceinografia , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Fundo de Olho
11.
Front Endocrinol (Lausanne) ; 13: 984561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093071

RESUMO

Objectives: The relationship between renal function and diabetic retinopathy has been controversial. This study is to investigate the influence of renal function on the complex and surgical outcomes of proliferative diabetic retinopathy (PDR). Methods: This was a post hoc analysis of the CONCEPT clinical trial. A total of 45 eyes with PDR underwent vitrectomy were included. Based on the estimated glomerular filtration rate (eGFR), they were divided into abnormal renal function group (ARF group) and normal renal function group (NRG group). Baseline PDR complex, intraoperative outcomes (Intraoperative bleeding, frequency of endodiathermy, surgical time, iatrogenic hole, and tamponade) and postoperative outcomes (logMAR best-corrected visual acuity, vitreous re-hemorrhage, and macular edema, follow up at postoperative 1 month and 3 months) were estimated. Vitreous, aqueous humor and serum were collected at the vitrectomy day and Vascular endothelia growth factor-A levels were quantified for all included patients using liquid chip method. Results: There was no significant difference in baseline PDR complex, intraoperative and postoperative outcomes between ARF group and NRG group (all P > 0.05). At the vitrectomy day, there was also no difference of Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups (all P > 0.05). Conclusion: Our results showed that the renal function seems not parallel to the severity of PDR, neither to the surgical outcomes. This might be interpreted by the similar Vascular endothelia growth factor-A levels in vitreous, aqueous humor and serum between the two groups.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Retinopatia Diabética/cirurgia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Rim/fisiologia , Rim/cirurgia , Resultado do Tratamento , Vitrectomia/métodos , Hemorragia Vítrea/cirurgia
12.
Front Med (Lausanne) ; 9: 794045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847781

RESUMO

Purpose: To develop artificial intelligence (AI)-based deep learning (DL) models for automatically detecting the ischemia type and the non-perfusion area (NPA) from color fundus photographs (CFPs) of patients with branch retinal vein occlusion (BRVO). Methods: This was a retrospective analysis of 274 CFPs from patients diagnosed with BRVO. All DL models were trained using a deep convolutional neural network (CNN) based on 45 degree CFPs covering the fovea and the optic disk. We first trained a DL algorithm to identify BRVO patients with or without the necessity of retinal photocoagulation from 219 CFPs and validated the algorithm on 55 CFPs. Next, we trained another DL algorithm to segment NPA from 104 CFPs and validated it on 29 CFPs, in which the NPA was manually delineated by 3 experienced ophthalmologists according to fundus fluorescein angiography. Both DL models have been cross-validated 5-fold. The recall, precision, accuracy, and area under the curve (AUC) were used to evaluate the DL models in comparison with three types of independent ophthalmologists of different seniority. Results: In the first DL model, the recall, precision, accuracy, and area under the curve (AUC) were 0.75 ± 0.08, 0.80 ± 0.07, 0.79 ± 0.02, and 0.82 ± 0.03, respectively, for predicting the necessity of laser photocoagulation for BRVO CFPs. The second DL model was able to segment NPA in CFPs of BRVO with an AUC of 0.96 ± 0.02. The recall, precision, and accuracy for segmenting NPA was 0.74 ± 0.05, 0.87 ± 0.02, and 0.89 ± 0.02, respectively. The performance of the second DL model was nearly comparable with the senior doctors and significantly better than the residents. Conclusion: These results indicate that the DL models can directly identify and segment retinal NPA from the CFPs of patients with BRVO, which can further guide laser photocoagulation. Further research is needed to identify NPA of the peripheral retina in BRVO, or other diseases, such as diabetic retinopathy.

13.
Opt Lett ; 47(14): 3515-3518, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838717

RESUMO

An acoustic coupling scheme largely determines the performance of optical-resolution photoacoustic microscopy (OR-PAM), including practicability, sensitivity, and stability. In this study, we propose OR-PAM based on a local-flexible acoustic coupling scheme, which includes a well-designed combiner connecting a set of circulating systems. The combiner integrates an objective lens and an ultrasonic transducer, controls the water level, restricts the flow rate, and drains bubbles. The circulating system provides sustained and steady flowing water. The flowing water constrained in the combiner and the circulating system forms a flexible and stable local contact between the sample and the transducer. Phantom experiments demonstrate that the proposed method can maintain high optical resolution but improve the detection sensitivity by approximately 1.9 times in comparison to dry coupling. In vivo imaging experiments of the mouse eyeground are conducted to examine the practicability of the proposed system in biomedicine. Moreover, in vivo experiments show that OR-PAM based on local-flexible coupling can reveal more details of eyeground microvasculatures, benefiting from its enhanced sensitivity. These merits promise that OR-PAM based on local-flexible coupling may have broad applications in biomedical fields.


Assuntos
Lentes , Técnicas Fotoacústicas , Animais , Camundongos , Microscopia/métodos , Técnicas Fotoacústicas/métodos , Análise Espectral , Água
14.
Front Physiol ; 13: 846003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309074

RESUMO

Purpose: To investigate the influence of preoperative adjunctive anti-VEGF drug (Conbercept) on vitreous inflammatory cytokines and chemokines profiles and whether those cytokines were associated with early macular edema (ME) after surgery for patients with proliferative diabetic retinopathy (PDR). Methods: In this post hoc analysis of the CONCEPT clinical trial, subjects with PDR underwent vitrectomy were included and vitreous samples were collected at the start of vitrectomy. Levels of vitreous VEGF, 17 inflammatory cytokines, and 11 chemokines were measured using Luminex multiplex technology. Subjects were then divided into groups based on with (Pre-IV) or without (No-Pre-IV) preoperative intravitreous injection of Conbercept; with or without early ME after surgery. Results: There was no difference between Pre-IV (13/30) and No-Pre-IV (7/29) concerning the ratio of patients with early ME (p = 0.17). After preoperative intravitreous injection of Conbercept, VEGF level dramatically decreased (p = 0.001), TNF-α (p = 0.002), and IP-10 (p = 0.018) increased in Pre-IV group. In patients with early ME after surgery, however, a number of cytokines increased, including IL-1ß (p = 0.008), IL-2 (p = 0.023), IL-4 (p = 0.030), IL-9 (p = 0.02), IL-10 (p = 0.002), IL-12 (p = 0.001), IL-13 (p = 0.031), IL-17A (p = 0.008), TNF-α (p = 0.012), CXCL9 (p = 0.023), G-CSF (p = 0.019), MCP-1 (p = 0.048), and RANTES (p = 0.016). Conclusion: We found the preoperative adjunctive Conbercept injection has limited influence on the levels of vitreous inflammatory cytokines and chemokines in PDR. The elevated levels of a series of cytokines might be associated with early inflammation after vitrectomy, which may lead to postoperative ME.

15.
J Ophthalmol ; 2022: 3242747, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35190775

RESUMO

PURPOSE: To evaluate the efficacy and safety of vitrectomy with inverted fovea-sparing internal limiting membrane, as a modified surgical technique in the treatment of the eyes with myopic foveoschisis. METHODS: This study was based on a consecutive, interventional case series. A standard 25-gauge (25-G), 3-port pars plana vitrectomy combined with inverted fovea-sparing internal limiting membrane was performed on 13 eyes. Preoperative and postoperative best-corrected visual acuity, optical coherence tomography image, and central foveal thickness were analyzed. Patients were followed up for at least 6 months. RESULTS: All 13 eyes showed dramatical resolution of myopic foveoschisis during the follow-up. The mean logarithm of minimum angle of resolution best-corrected visual acuity showed remarkable improvement from 1.06 ± 0.42 to 0.45 ± 0.25 (p < 0.0001; paired t-test). The mean central foveal thickness significantly decreased from 479.62 ± 113.16 µm to 372.38 ± 88.12 µm, 316.18 ± 73.97 µm, and 272.40 ± 61.32 µm postoperatively at 1 month, 3 months, and 6 months, respectively (p < 0.0001; paired t-test; preoperation vs. latest follow-up). CONCLUSIONS: Vitrectomy with inverted fovea-sparing internal limiting membrane can resolve myopic foveoschisis with high efficacy and safety.

16.
Mol Ther Nucleic Acids ; 27: 491-504, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35036060

RESUMO

Diabetic retinopathy is a heterogeneous retinal degenerative disease with the microvascular dysfunction being recognized as a hallmark of the advanced stage. In this study, we demonstrated that exosomes collected from the vitreous humor of proliferative diabetic retinopathy patients promoted proliferation, migration and tube formation ability of primary human retinal endothelial cells via its elevated miR-9-3p expression level. Müller glia cells were further recognized as the sole source of the aberrantly expressed miR-9-3p, and both in vitro and in vivo experiments validated that Müller glia-derived exosomes aggravate vascular dysfunction under high glucose. Mechanistically, exosomal miRNA-9-3p was transferred to retinal endothelial cells and bound to the sphingosine-1-phosphate receptor S1P1 coding sequence, which subsequently activated VEGFR2 phosphorylation and internalization in the presence or absence of exogenous VEGF-A. We successfully orchestrated the dynamic crosstalk between retinal Müller glia cells and endothelial cells in pathological condition, which may provide a novel biomarker or promising therapeutic agents for the treatment of diabetic retinopathy.

17.
Diabetes ; 71(4): 762-773, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35061025

RESUMO

Vitreous fibrovascular membranes (FVMs), the hallmark of proliferative diabetic retinopathy (PDR), cause retinal hemorrhage, detachment, and eventually blindness. However, little is known about the pathophysiology of FVM. In this study, we used single-cell RNA sequencing on surgically harvested PDR-FVMs and generated a comprehensive cell atlas of FVM. Eight cellular compositions were identified, with microglia as the major cell population. We identified a GPNMB+ subpopulation of microglia, which presented both profibrotic and fibrogenic properties. Pseudotime analysis further revealed the profibrotic microglia was uniquely differentiated from retina-resident microglia and expanded in the PDR setting. Ligand-receptor interactions between the profibrotic microglia and cytokines upregulated in PDR vitreous implicated the involvement of several pathways, including CCR5, IFNGR1, and CD44 signaling, in the microglial activation within the PDR microenvironment. Collectively, our description of the novel microglia phenotypes in PDR-FVM may offer new insight into the cellular and molecular mechanism underlying the pathogenesis of DR, as well as potential signaling pathways amenable to disease-specific intervention.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Citocinas/metabolismo , Diabetes Mellitus/metabolismo , Retinopatia Diabética/metabolismo , Humanos , Glicoproteínas de Membrana/genética , Microglia , Transcriptoma , Corpo Vítreo/metabolismo
19.
Acta Ophthalmol ; 100(3): e726-e736, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34260829

RESUMO

PURPOSE: To monitor the intraocular proangiogenic and profibrotic cytokine profiles within 7 days after intravitreous injection of conbercept (IVC) for patients with proliferative diabetic retinopathy (PDR). METHODS: This prospective, randomized controlled, consecutive, comparative study included 157 eyes with PDR. Participant eyes underwent sham IVC or IVC and subsequent vitrectomy at days 2, 3, 4, 5, 6, 7 postinjection. The intraocular cytokines profiles were measured using beaded assay methods. RESULTS: After IVC, the vascular endothelial growth factor (VEGF)-A level in PDR vitreous decreased rapidly by approximately 10 times at day 2 (p = 0.00001) and kept at a low level at days 3, 4, 5, 6, 7 (p < 0.001, each compared with IVC-sham group). Similar tendency of the change in VEGF-A was observed in aqueous humour. The level of placenta growth factor (PIGF) in aqueous humour decreased 2 days after IVC whereas returned to baseline level after 5 days. The vitreous profibrotic cytokines, tissue growth factor (TGF)-ß1, TGF-ß2, TGF-ß3 and connective tissue growth factor did not increase after IVC in each group. CONCLUSION: We observed a remarkable and rapid decrease in intraocular VEGF-A, temporal decrease in PIGF from day 2 to day 4, increase in VEGF-C and VEGF-D from day 2 onwards, but no profibrotic switch in PDR eyes after IVC. The findings might suggest that ideal vitrectomy timing might be around 3 days after IVC.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Citocinas/metabolismo , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Injeções Intravítreas , Fator de Crescimento Placentário , Estudos Prospectivos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vitrectomia/métodos
20.
Int J Ophthalmol ; 14(9): 1408-1412, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540618

RESUMO

AIM: To explore retinal displacement after surgical treatment for idiopathic macular hole (IMH) with different internal limiting membrane (ILM) peeling patterns. METHODS: Totally 22 eyes from 20 patients with IMH were randomly allocated into two groups, N-T group (11 eyes) and T-N group (11 eyes). For patients in N-T group, ILM was peeled off from nasal to temporal retina. For patients in T-N group, ILM was peeled off from temporal to nasal retina. Preoperative, postoperative 1, 3, and 6mo, autofluorescence fundus images were collected for manual measurement of distances of fixed nasal (N), temporal (T), superior (S), and inferior (I) retinal points (bifurcation or crossing of retinal vessels) around the macula to the optic disc (OD). These were respectively defined as N-OD, T-OD, S-OD, and I-OD. The retinal displacement, macular hole closure rate, and best corrected visual acuity (BCVA) were compared between the two groups after surgery. RESULTS: At postoperative 1, 3, and 6mo, the macula slipped toward the OD, manifested by the decreased T-OD, N-OD, S-OD, and I-OD (P<0.05). No significant difference was found in the T-OD, N-OD, S-OD, and I-OD between N-T group and T-N group. IMH closure rate was 100% both in N-T group and T-N group. There was no significant difference in BCVA between two groups (P<0.05). CONCLUSION: The macula slips toward the OD after successful macular hole surgery. The two different ILM peeling pattern show similar visual outcome and retinal displacement, which means ILM peeling directions are not the influencing factor of postoperative retinal displacement.

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