DIA-Based Quantitative Proteome Profiling of Aqueous Humor of Diabetic Retinopathy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Qianli Meng
PROVIDER: PXD046630 | iProX | Fri Nov 03 00:00:00 GMT 2023
REPOSITORIES: iProX
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Project description:Diabetic retinopathy (DR) is a leading cause of irreversible vision impairment and blindness. To explore the dynamics of aqueous humor (AH) protein profiles during four stages from non-diabetic individuals to proliferative diabetic retinopathy patients, especially to improve our understanding of pathophysiological mechanisms of proliferative diabetic retinopathy (PDR).
2024-07-04 | PXD053634 |
Project description:Diabetic retinopathy (DR) is a leading cause of blindness in adults under 40 in the developed world, with a significant proportion progressing to vision-threatening stages like proliferative diabetic retinopathy (PDR) and neovascular glaucoma (NVG). This study aims to explore the molecular mechanisms underlying the progression from non-proliferative DR (NPDR) to PDR and NVG, focusing on identifying potential biomarkers and therapeutic targets. We utilized discovery-based proteomics, specifically label free quantification (LFQ), to analyze aqueous humor (AH) proteins from patients with NPDR, PDR, and NVG from the AH samples obtained during cataract surgery or anterior chamber paracentesis. We employed triple quadrupole (QQQ)-MS for targeted protein quantification to validate marker proteins for each disease state. Notably,subsequent analyses revealed specific proteins associated with each stage of DR. Gene ontology analysis and functional annotation unveiled significant processes in DR such as immune response and lipid metabolic process. Validation of potential biomarkers revealed proteins showing significant concentration changes, with several candidates demonstrating diagnostic potential through ROC curve analysis. These findings provide insights into the biomarkers and pathogenesis of these severe neovascular complications. The identification of specific proteins associated with the progression of DR to more advanced stages offer a promising avenue for early diagnosis and targeted therapy. The study underscores the potential of AH proteomics in understanding complex diseases like DR and its complications.
2025-05-01 | PXD058481 | Pride
Project description:To investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal aflibercept (IVA) treatment in patients with proliferative diabetic retinopathy (PDR) patients. 5 PDR patients provided 10 samples of AH before and after IVA treatment (pre-group vs post-group). Proteins were identified using liquid chromatography-tandem mass spectrometry. Then, bioinformatics was employed to investigate the functional significance of differentially expressed proteins (DEPs) and hub proteins.
2024-05-21 | PXD039210 | Pride
Project description:Proliferative diabetic retinopathy (PDR) is a vision-threatening disorder characterized by the formation of cicatricial fibrovascular membranes leading to traction retinal detachment. Despite the recent advance in the treatment of PDR such as vitreoretinal surgery with use of anti-vascular endothelial growth factor (VEGF) drug as an adjunct, it still remains vision-threatening disease. In order to identify genes associated with the pathogenesis of PDR, we performed gene expression analyses in fibrovascular membrane in patients with PDR using DNA microarray technology.
2014-08-16 | GSE60436 | GEO
Project description:Proliferative diabetic retinopathy (PDR) is the advanced stage of diabetic retinopathy (DR), coupling with irregular neovascularization, and is the leading cause of blindness in working-age people; but the molecular mechanism of vascular differentiation in PDR remains poorly characterized. In our study, we obtained the transcriptome profile of neovascular proliferative membrane specimens from patients with PDR via high-throughput sequencing and advanced bioinformatics. Marker genes of neovascularization were validated and distinct gene expression patterns were formed of PDR compared with normal retina. We also discovered gene sets that were co-expressed with vascular endothelial growth factor A (VEGFA), including transcription factors (TFs) that dysregulate VEGFA. In particular, ETS transcription factors family could negatively regulate VEGFA. We also detected a set of genes related to PDR was dramatically changed from pre-mRNA to mature mRNA. In summary, our study firstly presented the profile of neovascular proliferative membrane and identified new marker genes and key regulators of VEGFA, which could contribute the molecular therapy of PDR in the future.
2020-08-10 | GSE102485 | GEO
Project description:Proliferative diabetic retinopathy (PDR) is a vision-threatening disorder characterized by the formation of cicatricial fibrovascular membranes leading to traction retinal detachment. Despite the recent advance in the treatment of PDR such as vitreoretinal surgery with use of anti-vascular endothelial growth factor (VEGF) drug as an adjunct, it still remains vision-threatening disease. In order to identify genes associated with the pathogenesis of PDR, we performed gene expression analyses in fibrovascular membrane in patients with PDR using DNA microarray technology. This study was approved by the Ethics Committee of the Kyushu University Hospital and Fukuoka University Chikushi Hospital, and the surgical specimens were handled in accordance with the ethical standards of the 1989 Declaration of Helsinki. All patients gave informed consent before inclusion in the study. Fibrovascular membranes (FVMs) were surgically dissected from the retinal surface with horizontal scissors of patients with PDR undergoing pars plana vitrectomy. These specimens were classified into active and inactive according to the clinical findings of neovascularization (NV) in the FVMs.Total RNA were extracted from the FVMs. RNA from human retina was obtained from Clontech (Palo Alto, CA).
2014-08-16 | E-GEOD-60436 | biostudies-arrayexpress
Project description:PURPOSE: To investigate the circulatory microRNA (miRNA) profiles of aqueous, vitreous, and plasma in order to identify biomarkers in aqueous humor or plasma that are reflecting changes in vitreous of patients with diabetes. METHODS: Aqueous, vitreous and plasma samples were collected from a total of 27 patients - 11 controls (macular pucker or macular hole patients) and 16 patients with diabetes mellitus (DM) undergoing vitreoretinal surgery: DM-Type I with proliferative diabetic retinopathy (PDR) (DMI-PDR), DM Type II with PDR (DMII-PDR) and DM Type II with nonproliferative DR (DMII-NPDR). MiRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, labeled with FlashTag kit, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data analysis was done using Expression Console (EC), Transcriptome Analysis Console (TAC), and Ingenuity Pathway Analysis (IPA) software. RESULTS: Our comparison of circulatory miRNA population of aqueous and vitreous humor and plasma showed that out of total of 847 human miRNA probes on the Affymetrix GeneChip miRNA 3.0 we found common miRNAs for both aqueous and vitreous samples, as well as larger number of unique miRNA, dependent on the DM type and presence of retinopathy. Most of the dysregulated miRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, most of the DM-specific miRNAs were downregulated. Dysregulation of miRNAs in aqueous generally do not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although we did identify a few candidates for common biomarkers: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed a set of miRNA that is uniquely dysregulated in each fluid, for example in aqueous samples for DMII-NPDR it was miR-455-3p, for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202. Pathway analysis identified TGF-beta and VEGF pathways as the common targets for miRNAs dysregulated in DR aqueous and vitreous. CONCLUSIONS: The comparative profiling of circulatory miRNAs in aqueous, vitreous, and plasma showed that a small number of circulatory miRNAs displayed differential presence in controls vs. diabetic retinopathy. A pattern is emerging of sets of miRNA that are common or uniquely dysregulated in the blood plasma or ocular fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for identifying diagnostic and therapeutic targets.
2020-06-27 | GSE140959 | GEO
Project description:We identified lncRNA expression profiles in vitreous samples between proliferative diabetic retinopathy (PDR) patients and idiopathic macular hole (IMH) patients, and between PDR patients who had received preoperative anti-vascular endothelial growth factor (anti-VEGF) therapy and PDR patients who had received surgery alone. There had been the systemic expression differences in vitreous at the microarray level from PDR patients and IMH patients, and from PDR patients after anti-VEGF treatment and untreated PDR patients.
2022-07-15 | GSE191210 | GEO
Project description:To investigate the key regulators of the disease by comparing the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and the controls with idiopathic epiretinal membrane (iERM).
2021-07-26 | PXD027556 |
Project description:Despite great advancements in proliferative diabetic retinopathy (PDR) therapy over the last decades, one third of treated patients continue to lose vision. Vitreous macrophages called hyalocytes have been implied in the pathogenesis of vitreoretinal proliferative disease previously but little is known about their role in PDR. In this study, we address molecular and cellular alterations of the PDR vitreous, in order to assess the potential contribution of hyalocytes to PDR development. A total of 55 patients were included in this study encompassing RNA-Sequencing analysis of vitreous hyalocytes from PDR and control patients, multiplex immunoassay and ELISA analysis of undiluted vitreous samples and isolation and immunohistochemical staining of cultured porcine hyalocytes. Our transcriptional analysis revealed an enhanced inflammatory signature of hyalocytes contributing to the cytokine pool within the PDR vitreous by expressing, among others, interleukin-6. The data further indicate an expression shift, involving angiopoietin-2, in PDR hyalocytes converting them to a proangiogenic cellular component, which may mediate formation of retinal neovascularization, hallmark of PDR. Finally, our data suggest a role of vitreous macrophages in erythrophagocytosis and, thereby, removal of vitreous hemorrhage, a severe complication of PDR. Immunomodulation of hyalocytes may thus prove an essential novel therapeutical approach in diabetic vitreoretinal disease.
2024-12-06 | GSE276892 | GEO