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1.
IEEE Trans Med Imaging ; PP2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587957

RESUMO

Accurate retinal layer segmentation on optical coherence tomography (OCT) images is hampered by the challenges of collecting OCT images with diverse pathological characterization and balanced distribution. Current generative models can produce high-realistic images and corresponding labels without quantitative limitations by fitting distributions of real collected data. Nevertheless, the diversity of their generated data is still limited due to the inherent imbalance of training data. To address these issues, we propose an image-label pair generation framework that generates diverse and balanced potential data from imbalanced real samples. Specifically, the framework first generates diverse layer masks, and then generates plausible OCT images corresponding to these layer masks using two customized diffusion probabilistic models respectively. To learn from imbalanced data and facilitate balanced generation, we introduce pathological-related conditions to guide the generation processes. To enhance the diversity of the generated image-label pairs, we propose a potential structure modeling technique that transfers the knowledge of diverse sub-structures from lowly- or non-pathological samples to highly pathological samples. We conducted extensive experiments on two public datasets for retinal layer segmentation. Firstly, our method generates OCT images with higher image quality and diversity compared to other generative methods. Furthermore, based on the extensive training with the generated OCT images, downstream retinal layer segmentation tasks demonstrate improved results. The code is publicly available at: https://github.com/nicetomeetu21/GenPSM.

2.
Med Image Anal ; 93: 103092, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325155

RESUMO

Optical coherence tomography angiography (OCTA) is a novel imaging modality that has been widely utilized in ophthalmology and neuroscience studies to observe retinal vessels and microvascular systems. However, publicly available OCTA datasets remain scarce. In this paper, we introduce the largest and most comprehensive OCTA dataset dubbed OCTA-500, which contains OCTA imaging under two fields of view (FOVs) from 500 subjects. The dataset provides rich images and annotations including two modalities (OCT/OCTA volumes), six types of projections, four types of text labels (age/gender/eye/disease) and seven types of segmentation labels (large vessel/capillary/artery/vein/2D FAZ/3D FAZ/retinal layers). Then, we propose a multi-object segmentation task called CAVF, which integrates capillary segmentation, artery segmentation, vein segmentation, and FAZ segmentation under a unified framework. In addition, we optimize the 3D-to-2D image projection network (IPN) to IPN-V2 to serve as one of the segmentation baselines. Experimental results demonstrate that IPN-V2 achieves an about 10% mIoU improvement over IPN on CAVF task. Finally, we further study the impact of several dataset characteristics: the training set size, the model input (OCT/OCTA, 3D volume/2D projection), the baseline networks, and the diseases. The dataset and code are publicly available at: https://ieee-dataport.org/open-access/octa-500.


Assuntos
Angiografia , Tomografia de Coerência Óptica , Humanos , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem
3.
Int J Gen Med ; 17: 447-456, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333017

RESUMO

Silicone oil has emerged as the common option for intraocular tamponade during complicated retina vitrectomy. However, the postoperative elevation of intraocular pressure (IOP), influenced by numerous factors, remains a significant and frequently encountered complication that poses a potential threat to vision. Extensive research has been conducted to investigate the risk factors associated with elevated IOP following silicone oil tamponade, including silicone oil viscosity, preoperative high IOP, diabetes, and lens status. This comprehensive review aims to gather and summarize the current research findings regarding the risk factors contributing to IOP elevation following silicone oil tamponade, as well as the optimal management strategies for secondary glaucoma. The analysis includes the physicochemical properties of silicone oil, preoperative and intraoperative risk factors, and the effective management of secondary glaucoma. Enhancing our understanding of the primary factors associated with silicone oil-induced IOP elevation will facilitate the guidance of timely and appropriate interventions.

4.
EMBO Mol Med ; 16(2): 294-318, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38297099

RESUMO

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Quinase 2 Dependente de Ciclina , Diabetes Mellitus , Retinopatia Diabética , Animais , Camundongos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Células Endoteliais/metabolismo , Retina/metabolismo , RNA , Peixe-Zebra/genética
5.
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
6.
IEEE Trans Med Imaging ; 42(1): 329, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37747846

RESUMO

In the above article [1], there is an error in (3). Instead of [Formula: see text] It should be [Formula: see text].

7.
Cell Rep ; 42(7): 112779, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37436898

RESUMO

Retinal pigment epithelium (RPE) dysfunction and choroidal neovascularization (CNV) are predominant features of age-related macular degeneration (AMD), with an unclear mechanism. Herein, we show that RNA demethylase α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) is up-regulated in AMD. In RPE cells, ALKBH5 overexpression associates with depolarization, oxidative stress, disturbed autophagy, irregular lipid homeostasis, and elevated VEGF-A secretion, which subsequently promotes proliferation, migration, and tube formation of vascular endothelial cells. Consistently, ALKBH5 overexpression in mice RPE correlates with various pathological phenotypes, including visual impairments, RPE anomalies, choroidal neovascularization (CNV), and interrupted retinal homeostasis. Mechanistically, ALKBH5 regulates retinal features through its demethylation activity. It targets PIK3C2B and regulates the AKT/mTOR signaling pathway with YTHDF2 as the N6-methyladenosine reader. IOX1, an ALKBH5 inhibitor, suppresses hypoxia-induced RPE dysfunction and CNV progression. Collectively, we demonstrate that ALKBH5 induces RPE dysfunction and CNV progression in AMD via PIK3C2B-mediated activation of the AKT/mTOR pathway. Pharmacological inhibitors of ALKBH5, like IOX1, are promising therapeutic options for AMD.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase , Neovascularização de Coroide , Degeneração Macular , Animais , Camundongos , Neovascularização de Coroide/metabolismo , Células Endoteliais/metabolismo , Degeneração Macular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Homólogo AlkB 5 da RNA Desmetilase/metabolismo
8.
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
9.
J Biomed Res ; 37(5): 367-381, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37366063

RESUMO

Age-related macular degeneration (AMD) causes irreversible blindness in people aged over 50 worldwide. The dysfunction of the retinal pigment epithelium is the primary cause of atrophic AMD. In the current study, we used the ComBat and Training Distribution Matching method to integrate data obtained from the Gene Expression Omnibus database. We analyzed the integrated sequencing data by the Gene Set Enrichment Analysis. Peroxisome and tumor necrosis factor-α (TNF-α) signaling and nuclear factor kappa B (NF-κB) were among the top 10 pathways, and thus we selected them to construct AMD cell models to identify differentially expressed circular RNAs (circRNAs). We then constructed a competing endogenous RNA network, which is related to differentially expressed circRNAs. This network included seven circRNAs, 15 microRNAs, and 82 mRNAs. The Kyoto Encyclopedia of Genes and Genomes analysis of mRNAs in this network showed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway was a common downstream event. The results of the current study may provide insights into the pathological processes of atrophic AMD.

10.
IEEE J Biomed Health Inform ; 27(5): 2432-2443, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37028061

RESUMO

Large volume of labeled data is a cornerstone for deep learning (DL) based segmentation methods. Medical images require domain experts to annotate, and full segmentation annotations of large volumes of medical data are difficult, if not impossible, to acquire in practice. Compared with full annotations, image-level labels are multiple orders of magnitude faster and easier to obtain. Image-level labels contain rich information that correlates with the underlying segmentation tasks and should be utilized in modeling segmentation problems. In this article, we aim to build a robust DL-based lesion segmentation model using only image-level labels (normal v.s. abnormal). Our method consists of three main steps: (1) training an image classifier with image-level labels; (2) utilizing a model visualization tool to generate an object heat map for each training sample according to the trained classifier; (3) based on the generated heat maps (as pseudo-annotations) and an adversarial learning framework, we construct and train an image generator for Edema Area Segmentation (EAS). We name the proposed method Lesion-Aware Generative Adversarial Networks (LAGAN) as it combines the merits of supervised learning (being lesion-aware) and adversarial training (for image generation). Additional technical treatments, such as the design of a multi-scale patch-based discriminator, further enhance the effectiveness of our proposed method. We validate the superior performance of LAGAN via comprehensive experiments on two publicly available datasets (i.e., AI Challenger and RETOUCH).


Assuntos
Edema , Tomografia de Coerência Óptica , Humanos , Processamento de Imagem Assistida por Computador
11.
Differentiation ; 132: 51-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37069005

RESUMO

Retinal development is initiated by multipotent retinal progenitor cells, which undergo several rounds of cell divisions and subsequently terminal differentiation. Retinal regeneration is usually considered as the recapitulation of retinal development, which share common mechanisms underlying the cell cycle re-entry of adult retinal stem cells and the differentiation of retinal neurons. However, how proliferative retinal progenitor cells perform a precise transition to postmitotic retinal cell types during the process of development and regeneration remains elusive. It is proposed that both the intrinsic and extrinsic programming are involved in the transcriptional regulation of the spatio-temporal fate commitment. Epigenetic modifications and the regulatory mechanisms at both DNA and chromatin levels are also postulated to play an important role in the timing of differentiation of specific retinal cells. In the present review, we have summarized recent knowledge of epigenetic regulation that underlies the commitment of retinal progenitor cells in the settings of retinal development and regeneration.


Assuntos
Epigênese Genética , Retina , Diferenciação Celular/genética , Células-Tronco , Neurônios
12.
J Pers Med ; 13(2)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36836523

RESUMO

(1) Background: The microstructural alterations of the peripapillary choriocapillaris in high myopes remain elusive. Here, we used optical coherence tomography angiography (OCTA) to explore factors involved in these alterations. (2) Methods: This cross-sectional control study included 205 young adults' eyes (95 with high myopia and 110 with mild to moderate myopia). The choroidal vascular network was imaged using OCTA, and the images underwent manual adjustments to determine the peripapillary atrophy (PPA)-ß zone and microvascular dropout (MvD). The area of MvD and the PPA-ß zone, spherical equivalent (SE), and axial length (AL) were collected and compared across groups. (3) Results: The MvD was identified in 195 eyes (95.1%). Highly myopic eyes exhibited a significantly greater area for the PPA-ß zone (1.221 ± 0.073 vs. 0.562 ± 0.383 mm2, p = 0.001) and MvD (0.248 ± 0.191 vs. 0.089 ± 0.082 mm2, p < 0.001) compared with mildly to moderately myopic eyes, and a lower average density in the choriocapillaris. Linear regression analysis showed that the MvD area correlated with age, SE, AL, and the PPA-ß area (all p < 0.05). (4) Conclusions: This study found that MvDs represent choroidal microvascular alterations in young-adult high myopes, which were correlated with age, SE, AL, and the PPA-ß zone. In this disorder, OCTA is important for characterizing the underlying pathophysiological adaptations.

13.
Front Pharmacol ; 14: 1138452, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843929

RESUMO

Background: Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM. Methods: Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms. Results: Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays. Conclusion: The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.

14.
Exp Eye Res ; 228: 109388, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36652968

RESUMO

In this study we described a new model of subretinal edema induced by single intraocular injection of DL-alpha-aminoadipic acid (DLAAA) that can be employed to study the mechanism of retinal edema and test the efficacy or potential toxicity of treatments. The progression of subretinal edema was evaluated by fundus photography, fluorescein angiography and optical coherence tomography for up to 4 weeks following DLAAA injection. The VEGF, IL-6, TNF-α, Occludin, ZO-1, AQP4, Kir4.1, GFAP and GS levels were examined in DLAAA models by immunostaining, immumohistochemical staining and Western blot. Additionally, bulk RNA-seq was used to detect the mechanism involved in DLAAA-induced retinal Müller cellular injuries. In vivo and vitro assays were further conducted to confirm the sequencing results. Subretinal edema was successfully induced by DLAAA in New Zealand White rabbits (1.29 mg/eye) and C57BL/6 mice (50 or 100 µg/eye). Our results demonstrated that the disruption of blood-retinal-barrier, including vascular hyperpermeability, inflammation, and Müller cell dysfunction of fluid clearance, was involved in subretinal edema formation in the model. Bulk RNA-seq and in vitro studies indicated the activation of p38 MAPK signaling pathway in DLAAA models. This DLAAA-induced subretinal edema model can be used for mechanistic studies or drug screening.


Assuntos
Ácido 2-Aminoadípico , Edema , Camundongos , Animais , Coelhos , Camundongos Endogâmicos C57BL , Angiofluoresceinografia/métodos , Barreira Hematorretiniana/fisiologia , Tomografia de Coerência Óptica/métodos
15.
Comput Methods Programs Biomed ; 230: 107364, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36716636

RESUMO

BACKGROUND AND OBJECTIVE: Most of the existing disease prediction methods in the field of medical image processing fall into two classes, namely image-to-category predictions and image-to-parameter predictions.Few works have focused on image-to-image predictions. Different from multi-horizon predictions in other fields, ophthalmologists prefer to show more confidence in single-horizon predictions due to the low tolerance of predictive risk. METHODS: We propose a single-horizon disease evolution network (SHENet) to predictively generate post-therapeutic SD-OCT images by inputting pre-therapeutic SD-OCT images with neovascular age-related macular degeneration (nAMD). In SHENet, a feature encoder converts the input SD-OCT images to deep features, then a graph evolution module predicts the process of disease evolution in high-dimensional latent space and outputs the predicted deep features, and lastly, feature decoder recovers the predicted deep features to SD-OCT images. We further propose an evolution reinforcement module to ensure the effectiveness of disease evolution learning and obtain realistic SD-OCT images by adversarial training. RESULTS: SHENet is validated on 383 SD-OCT cubes of 22 nAMD patients based on three well-designed schemes (P-0, P-1 and P-M) based on the quantitative and qualitative evaluations. Three metrics (PSNR, SSIM, 1-LPIPS) are used here for quantitative evaluations. Compared with other generative methods, the generative SD-OCT images of SHENet have the highest image quality (P-0: 23.659, P-1: 23.875, P-M: 24.198) by PSNR. Besides, SHENet achieves the best structure protection (P-0: 0.326, P-1: 0.337, P-M: 0.349) by SSIM and content prediction (P-0: 0.609, P-1: 0.626, P-M: 0.642) by 1-LPIPS. Qualitative evaluations also demonstrate that SHENet has a better visual effect than other methods. CONCLUSIONS: SHENet can generate post-therapeutic SD-OCT images with both high prediction performance and good image quality, which has great potential to help ophthalmologists forecast the therapeutic effect of nAMD.


Assuntos
Processamento de Imagem Assistida por Computador , Degeneração Macular , Humanos , Processamento de Imagem Assistida por Computador/métodos , Tomografia de Coerência Óptica/métodos , Degeneração Macular/diagnóstico por imagem
16.
Retina ; 43(11): 2045-2050, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35030148

RESUMO

PURPOSE: The purpose of this study was to investigate the clinical outcomes of an optimized method to clearly remove the subretinal proliferative tissue by transscleral puncture into the subretinal space in patients with grade C proliferative vitreoretinopathy without inducing retinal injury. METHODS: This was a prospective clinical observation study. Eight consecutive patients who had undergone optimized vitrectomy surgery for retinal detachment complicated by grade C proliferative vitreoretinopathy were investigated. Subretinal proliferation was cleared by adding one additional scleral 23-gauge trocar under the detached retina at 9 mm to 10 mm from the limbus. After the sclera is pierced, the puncture knife changed its direction without touching the retina. 23-G intraocular forceps were used to remove the proliferation strand or membrane through the puncture channel. RESULTS: Retinal reattachment was achieved in each case without a retinotomy. The mean best-corrected visual acuity was improved within the first 1 month ( P = 0.039) and remained stable at the following phase. There were no postoperative complications, such as reoccurrence of retinal detachment or proliferative vitreoretinopathy. No postoperative hemorrhage or hypotension was observed. CONCLUSION: The satisfying results demonstrated the feasibility of this cost-effective, easy-to-follow, transscleral vitrectomy method in treating retinal detachment with grade C proliferative vitreoretinopathy.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Humanos , Proliferação de Células , Estudos Prospectivos , Descolamento Retiniano/cirurgia , Acuidade Visual , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/cirurgia , Vitreorretinopatia Proliferativa/complicações
17.
Acta Pharmacol Sin ; 44(4): 897-912, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36280689

RESUMO

Anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular eye diseases, but responses are incomplete in some patients. Recent evidence shows that integrins are involved in the pathogenesis of neovascular age-related macular degeneration and diabetic retinopathy. JP1, derived from an optimized seven-amino-acid fragment of JWA protein, is a polypeptide specifically targeting integrin αVß3. In this study we evaluated the efficacy of JP1 on laser-induced choroidal neovascularization (CNV) and retinal vascular leakage. CNV mice received a single intravitreal (IVT) injection of JP1 (10, 20, 40 µg) or ranibizumab (RBZ, 10 µg). We showed that JP1 injection dose-dependently inhibited laser-induced CNV; the effect of RBZ was comparable to that of 20 µg JP1; a combined IVT injection of JP1 (20 µg) and RBZ (5 µg) exerted a synergistic effect on CNV. In the 3rd month after streptozotocin injection, diabetic mice receiving IVT injection of JP1 (40 µg) or RBZ (10 µg) once a week for 4 weeks showed significantly suppressed retinal vascular leakage. In both in vivo and in vitro experiments, JP1 counteracted oxidative stress and inflammation via inhibiting ROS/NF-κB signaling in microglial cells, and angiogenesis via modulating MEK1/2-SP1-integrin αVß3 and TRIM25-SP1-MMP2 axes in vascular endothelial cells. In addition, intraperitoneal injection of JP1 (1, 5 or 10 mg) once every other day for 3 times also dose-dependently inhibited CNV. After intraperitoneal injection of FITC-labeled JP1 (FITC-JP1) or FITC in laser-induced CNV mice, the fluorescence intensity in the CNV lesion was markedly increased in FITC-JP1 group, compared with that in FITC group, confirming that JP1 could penetrate the blood-retinal barrier to target CNV lesion. We conclude that JP1 can be used to design novel CNV-targeting therapeutic agents that may replace current invasive intraocular injections.


Assuntos
Neovascularização de Coroide , Diabetes Mellitus Experimental , Retinopatia Diabética , Animais , Camundongos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Fluoresceína-5-Isotiocianato/uso terapêutico , Integrina alfaVbeta3/uso terapêutico , Peptídeos/uso terapêutico
18.
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
19.
Front Med (Lausanne) ; 10: 1340198, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264037

RESUMO

Background: To evaluate risk factors and further develop prediction models for intraocular pressure elevation (IOP) after vitreoretinal surgery with silicone oil tamponade to support clinical management. Methods: A retrospective study analyzed 1,061 eyes of 1,061 consecutive patients that presented to the Jiangsu Province Hospital between December 2015 and December 2020, the IOP was measured from the preoperative visit and at the 1-week, 1-month, 3-month, and 6-month visits, and the final postoperative visit before silicone oil removal. Four machine learning methods were used to carried out the prediction of IOP elevation: Decision Tree, Logistic Regression, Random Forest, and Gradient-Boosted Decision Trees (GBDT) based on features including demographic and clinical characteristics, preoperative factors and surgical factors. Predictors were selected based on the p-value of the univariate analysis. Results: Elevated intraocular pressure developed in 26.01% of the eyes postoperatively. Elevated intraocular pressure primarily occurred within 1-2 weeks after surgery. Additionally, the majority of IOP values were distributed around 25-40 mmHg. GBDT utilizing features with p-values less than 0.5 from the hypothesis testing demonstrated the best predictive performance for 0.7944 in accuracy. The analysis revealed that age, sex, hypertension, diabetes, myopia, retinal detachment, lens status and biological parameters have predictive value. Conclusion: Age, sex, hypertension, diabetes, myopia, retinal detachment, lens status and biological parameters have influence on postoperative intraocular pressure elevation for patients with silicone oil tamponade after pars plana vitrectomy. The prediction model showed promising accuracy for the occurrence of IOP elevation. This may have some reference significance for reducing the incidence of high intraocular pressure after pars plana vitrectomy combined with silicone oil filling.

20.
J Clin Med ; 11(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362727

RESUMO

Diabetic retinopathy (DR) is currently one of the common causes of vision loss in working-age adults. It is clinically diagnosed and classified according to the vascular changes in the fundus. However, the activation of immune cells occurs before these vascular changes become detectable. These, together with molecular studies and the positive clinical outcomes of anti-inflammatory treatment, highlight the pivotal involvement of the immune system. The role of innate immunity in DR pathophysiology has been studied in depth, but the contribution of adaptive immunity remains largely elusive. This review aims to summarize our current understanding of the activation mechanism of adaptive immunity in DR microenvironments and to discuss the relationship between adaptive immunity and local vascular units or innate immunity, which opens new avenues for clinical applications in DR treatment.

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