Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy.
Ontology highlight
ABSTRACT:
SUBMITTER: Loporchio DF
PROVIDER: S-EPMC8147162 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Purpose:To investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR). Methods:Vitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1β [MIP-1β], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection. Results:The following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-α, MCP-1, MIP-1β, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-α, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01). Conclusions:In this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.
| S-EPMC7326572 | biostudies-literature
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:Aims/hypothesisProliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR.MethodsWe analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration.ResultsWe identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024).Conclusions/interpretationThese results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR. Graphical abstract.
| S-EPMC7718434 | biostudies-literature
Project description:BackgroundDiabetes can lead to serious microvascular complications such as proliferative diabetic retinopathy (PDR), which results in severe vision loss. The diabetes-induced alterations in the vitreous protein composition in diabetic patients with PDR may be responsible for the presence of PDR. The vitreous humour can be utilised in a variety of studies aimed toward the discovery of new targets for the treatment or prevention of PDR and the identification of novel disease mechanisms. The aim of this study was to compare the protein profile of vitreous humour from diabetic patients with PDR with that of vitreous humour from normal human eyes donated for corneal transplant.ResultsVitreous humour from type 2 diabetic patients with PDR (n = 10) and from normal human eyes donated for corneal transplant (n = 10) were studied. The comparative proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Differentially produced proteins (abundance ratio > 2 or < -2, p < 0.01) were identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF tandem mass spectrometry. A total of 1242 protein spots were detected on the 2-D master gel of the samples, and 57 spots that exhibited statistically significant variations were successfully identified. The spots corresponded to peptide fragments of 29 proteins, including 8 proteins that increased and 21 proteins that decreased in PDR. Excluding the serum proteins from minor vitreous haemorrhage, 19 proteins were found to be differentially produced in PDR patients compared with normal subjects; 6 of these proteins have never been reported to be differentially expressed in PDR vitreous: N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH 1), tubulin alpha-1B chain, gamma-enolase, cytosolic acyl coenzyme A thioester hydrolase, malate dehydrogenase and phosphatidylethanolamine-binding protein 1 (PEBP 1). The differential production of pigment epithelium-derived factor (PEDF) and clusterin was confirmed by Western blot analysis.ConclusionsThese data provide an in-depth analysis of the human vitreous proteome and reveal protein alterations that are possibly involved in the pathogenesis of PDR. Further investigation of these special proteins may provide potential new targets for the treatment or the prevention of PDR.
| S-EPMC3310785 | biostudies-literature
Project description:PurposeTo determine the differences of metabolites and metabolic pathways between patients with proliferative diabetic retinopathy (PDR) and without diabetes (nondiabetic controls) in plasma and vitreous, respectively, and to characterize the relationship between plasma and vitreous metabolic profiles.MethodsLiquid chromatography/tandem mass spectrometry technology was performed to distinct metabolite profiles of plasma and vitreous. A total of 139 plasma samples from 88 patients with PDR and 51 nondiabetic controls, as well as 74 vitreous samples from 51 patients with PDR and 23 nondiabetic controls, were screened. Pathway analysis was performed using MetaboAnalyst 5.0. Pearson correlation analysis was used to investigate the correlation of metabolites in vitreous and plasma.ResultsAfter adjusting for age, fasting blood glucose, and urea, in vitreous metabolomes, a total of 76 features distinguished patients with PDR from controls. Fifteen differential metabolites were found in plasma metabolites. Pantothenate and CoA biosynthesis was the common metabolic pathway altered in both plasma and vitreous. Aromatic amino acid metabolism pathways were dysregulated in vitreous of PDR. For four metabolic features, there were positive correlations between vitreous and plasma.ConclusionsDespite great differences between the metabolic profiles of plasma and vitreous in PDR cases, there are also similarities in the change of metabolites and metabolic pathways. Exploring the relationship of metabolomics between vitreous and plasma may help provide new understanding of the mechanism of PDR.
| S-EPMC8842420 | biostudies-literature
Project description:Vitreous of proliferative diabetic retinopathy patients
| PRJNA790455 | ENA
Project description:Purpose: This study aims to determine vitamin D concentrations in the vitreous and serum, as well as the expression levels of NLRP3 inflammasome pathway in the vitreous of patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the possible correlation between NLRP3 inflammasome levels and vitamin D concentrations. Methods: We obtained vitreous samples before vitrectomy from 55 PDR patients, 25 non-diabetic patients with idiopathic macular hole (IMH), and 10 non-proliferative diabetic retinopathy (NPDR) patients. We also collected serum samples from the same patients. Enzyme-linked immunosorbent assay (ELISA) was used to examine NLRP3 inflammasome pathway proteins, including NLRP3, caspase-1, IL-1β, and VEGF. In addition, vitamin D concentrations were analyzed in Roche Cobas 6000's module e601 platform using electrochemiluminescence immune assay. Results: The levels of NLRP3 inflammasome pathway and VEGF increased dramatically in PDR vitreous. However, vitamin D concentrations in vitreous and serum followed the opposite trend. Meanwhile, vitreous and serum vitamin D concentrations were significantly negatively correlated with vitreous NLRP3 expression in PDR patients. Moreover, serum and vitreous vitamin D concentrations were positively correlated and demonstrated discriminatory ability in DR. The subgroup analysis of PDR group revealed that eyes with tractional retinal detachment (TRD) had higher NLRP3 inflammasome pathway and VEGF levels but lower vitamin D concentrations. Conversely, eyes that received preoperative pan-retinal photocoagulation (PRP) exhibited lower levels of NLRP3 inflammasome pathway, but vitamin D concentrations were irrelevant to laser treatment. Conclusions: Our results demonstrate a strong correlation between increased NLRP3 inflammasome pathway and decreased vitamin D concentrations in the vitreous of PDR patients, which may be linked to PDR pathogenesis. In addition, vitamin D supplementation may play a key role in preventing, treating, and improving PDR prognosis due to its inhibitory impact on NLRP3 inflammasome pathway and VEGF.
| S-EPMC8553965 | biostudies-literature
Project description:Evaluation of cytokines in patients with diabetic retinopathy (DR) is important for the identification of future additive or alternative treatment options. Therefore, vitreous samples were obtained from patients with DR and patients with macular hole or macular pucker (control group) during 23-gauge-vitrectomy (n = 17/group). The levels of three pro-inflammatory (IL-1ß, IL-6, IFN-γ) and pleiotropic cytokines (IL-2, IL-4, IL-13) as well as VEGF, VEGF-A, and PGF were measured using an enzyme linked immunosorbent assay (ELISA). IL-1ß (p = 0.02) and IFN-γ (p = 0.04), two of the three tested pro-inflammatory cytokines, were elevated in the DR patients, while IL-6 (p = 0.51) level was comparable in both groups. Moreover, in DR samples, a trend towards an IL-13 down-regulation (p = 0.36) was observable. The IL-2 (p = 0.62) and IL-4 (p = 0.78) levels were comparable in both groups. All analyzed angiogenetic factors were up-regulated in DR patients (VEGF: p<0.001; VEGF-A: p = 0.002; PGF: p<0.001). The up-regulation of angiogenetic factors underline their importance in DR development. However, the interaction of the other cytokines showed an interesting pattern. Pro-inflammatory cytokines were also up-regulated, which could be evidence for inflammation processes in the diabetic retina. Furthermore, it seems that a counter response of immunomodulatory cytokines is in an initial process, but not strong enough to regulate the processes. Therefore, to support these anti-inflammatory mechanisms might be additive treatment option in the future.
| S-EPMC5870958 | biostudies-literature
Project description:PurposeVitreous vitamin C, as an anti-oxidant, is responsible for regulating oxygen tension and oxidative stress in the eye. Oxidative stress and retinal ischemia are implicated in the development of proliferative diabetic retinopathy (PDR). In this study, we aimed to determine whether vitreous level of vitamin C is compromised in patients with PDR and to investigate the association of diabetic macular ischemia and vitamin C.MethodsThis prospective study enrolled forty patients who underwent pars plana vitrectomy for the treatment of PDR (PDR group, n = 20) and idiopathic epiretinal membrane (control group, n = 20). Serum, aqueous humor, and the vitreous were collected for the analysis of vitamin C level by HPLC. Diabetic macular ischemia (DMI) in PDR group was evaluated with fluorescein angiography (FA).ResultsPDR patients (60.4 ± 2.1 y) were younger than non-diabetic control patients (67.4 ± 1.2 y). Serum, aqueous, and vitreous levels of vitamin C in PDR were 38.7%, 22.5%, and 11.1% of non-diabetic control group, respectively. All PDR patients had DMI (grade 1: 25%, grade 2: 30%, grade 3: 30%, grade 4: 15%). DMI grade was inversely correlated with the level of vitreous vitamin C (r = -0.546, P = 0.019), not with HbA1C, serum, or aqueous vitamin C level. In addition, the level of vitreous vitamin C (4.5 ± 2.6 μg/ml) in high DMI group (Gr 3 &4) was lower than that (31.0 ± 9.1 μg/ml) in low DMI group (Gr 1&2) (P = 0.015).ConclusionsVitreous level of vitamin C in PDR patients showed a tenfold decrease, which was associated with the degree of macular ischemia. This suggests that vitreous vitamin C depletion may cause macula ischemia in PDR patients.
| S-EPMC6583975 | biostudies-literature
Project description:Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Systemic and intraocular factors are intricately related to PDR, and vitreous fluid (VF) cytokines are representative intraocular biomarkers. However, the associations between systemic factors and VF cytokines and their influence on PDR pathology are unclear. This study aimed to examine the correlation between systemic factors and VF cytokines and analyze their contributions to the pathology of PDR using multivariate analyses. We conducted a retrospective observational study on 26 PDR eyes of 25 patients with type 2 DM, and 30 eyes of 30 patients with idiopathic macular hole or epiretinal membrane as controls. Fifteen systemic and laboratory tests including blood pressure (BP) and body mass index (BMI), and 27 cytokines in VF were analyzed. BP and BMI correlated positively with VF levels of IL-6 and IP-10 in PDR patients, while no significant correlation was found between systemic factors and VF cytokines in controls. MCP-1 and VEGF-A in VF separately clustered with different systemic factors in controls, but these cytokines lost the property similarity with systemic factors and acquired property similarity with each other in PDR. Systemic factors contributed to only 10.4%, whereas VF cytokines contributed to 42.3% out of 52.7% variance of the whole PDR dataset. Our results suggest that intraocular factors play a major role in the pathology of PDR, whereas systemic factors may have limited effects, and that BP and BMI control in PDR could be useful interventions to improve intraocular immune condition.
| S-EPMC10059790 | biostudies-literature