Growth Factor In Aqueous Humor Research Articles

Concentrations of Selected Cytokines and Vascular Endothelial Growth Factor in Aqueous Humor and Serum of Diabetic Patients

ABSTRACTPurpose: To investigate the aqueous humor and serum levels of selected cytokines and vascular endothelial growth factor (VEGF) in diabetic patients, implicating their role in the pathogenesis of diabetic eye complications.Materials and methods: Atotal of 65 patients (27 males and 38 females) who underwent cataract surgery were recruited into the study. The study group consisted of 30 cataract patients with type 2 diabetes mellitus, and this group was divided into two subgroups: 14 patients with diabetic retinopathy (DR group) and 16 patients without DR (NDR group). The control group consisted of 35 non-diabetic cataract subjects.Results: Patients in the DR group had significantly higher aqueous humor concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, monocyte chemotactic protein (MCP-1) and VEGF. Likewise, serum concentrations of IL-1β, IL-6, IL-8, IL-12, TNF-α and IFN-γ were significantly higher in the DR group as compared to the controls. Aqueous humor concentrations of IL-1β, IL-8, MCP-1 and VEGF were significantly higher in the DR group as compared with the NDR group.Conclusion: Our findings support the hypothesis that chronic inflammation and a disturbance of the immune system play important roles in the pathogenesis of diabetic cataract and DR.

Usefulness of Liquid Biopsy Biomarkers from Aqueous Humor in Predicting Anti-VEGF Response in Diabetic Macular Edema: Results of a Pilot Study.

The objective was to investigate the usefulness of the “liquid biopsy” of aqueous humor (AH) to predict the clinical response after intravitreal injections (IVT) of anti-VEGF agents for treating diabetic macular edema (DME). For this purpose, AH samples obtained during the first anti-VEGF IVT from 31 type two diabetic patients were analyzed. Patients were classified into three groups according to their anti-VEGF response: rapid responders (n = 11), slow responders (n = 11), and non-responders (n = 9). In addition, patients (n = 7) who showed good response to corticosteroids but a delayed or no response to anti-VEGF therapy were analyzed. Levels of 17 different cytokines, chemokines, and growth factors in AH were measured using a multiplex immunoassay. We found higher concentrations of VEGF in rapid responders to anti-VEGF therapy compared to non-responders. In addition, slow responders to anti-VEGF treatment showed higher levels of inflammatory markers than rapid responders, but did not reach statistical significance. Finally, those patients who responded to corticosteroids but not to anti-VEGF therapy showed significantly lower levels of VEGF than patients with rapid response (p = 0.01). In conclusion, “liquid biopsy” of AH could be useful to determine whether the predominant pathogenic event is primarily angiogenic or inflammatory in nature. This approach would allow physicians to select a more rational and cost-effective treatment. Further studies to validate these preliminary results are warranted.

Profiling and Bioinformatic Analysis of Differentially Expressed Cytokines in Aqueous Humor of High Myopic Eyes – Clues for Anti-VEGF Injections

ABSTRACT Purpose To investigate the aqueous humor growth factor profile in high myopic eyes and analyze the interaction of differentially expressed cytokines. Methods A case–control study including aqueous humor samples from 36 high myopic patients and 32 controls was conducted. Quantibody® Human Growth Factor Array was used to screen the presence of 40 growth factors in aqueous humor. Expressions of differential growth factors were validated by Bio-Plex ProTM multiplex bead-based immunoassay. Protein–protein interaction (PPI) and gene ontology (GO) analyses were performed. Results Growth differentiation factor 15 (GDF-15), hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF)-AA were found to be significantly higher and vascular endothelial growth factor (VEGF) was detected to be lower in high myopic eyes (all P = .03). Multi-plex bead-based assay further validated the differential expressions of four growth factors and all of them were significantly correlated with axial length (P < .001). Twenty-six proteins were mapped into PPI network and positive regulation of cell migration, cellular component movement, and cell motility were the most enriched biological processes based on GO analysis. Conclusions Differential expressed cytokines that indicates a distinctive intraocular microenvironment in high myopic eyes might provide clues for pathological changes within high myopic eyes after anti-VEGF injections.

Expression of platelet-derived growth factor-C in aqueous humor of patients with neovascular glaucoma and its correlation with vascular endothelial growth factor.

The aim of this study was to investigate the expression of platelet-derived growth factor-C in aqueous humor of patients with neovascular glaucoma and its correlation with vascular endothelial growth factor. This study involved 62 eyes of 62 patients with advanced neovascular glaucoma requiring transscleral cyclophotocoagulation. Aqueous humor was collected through paracentesis. Samples from 11 eyes of 11 patients with age-related cataract were collected as control. Concentrations of platelet-derived growth factor-C and vascular endothelial growth factor in aqueous humor were quantified by enzyme-linked immunosorbent assay. Meanwhile, the correlations between the concentrations of platelet-derived growth factor-C and vascular endothelial growth factor were analyzed. The elements including retinal photocoagulation treatment, iris neovascularization grade, and primary fundus disease were also studied to find out their roles in the concentrations of the two factors. The vascular endothelial growth factor and platelet-derived growth factor-C concentrations in aqueous humor from controls were (679.54 ± 49.81) pg/mL and (18.60 ± 1.85) pg/mL, respectively. Both of them were significantly lower than neovascular glaucoma patients (p < 0.001). The vascular endothelial growth factor and platelet-derived growth factor-C concentrations of neovascular glaucoma patients treated with retinal photocoagulation were (1095.99 ± 52.71) pg/mL and (28.55 ± 0.94) pg/mL, respectively, which were both significantly lower than those of untreated neovascular glaucoma patients, (1146.28 ± 69.57) pg/mL and (30.04 ± 1.64) pg/mL (p = 0.008, p = 0.034). There was a weak correlation between the expression level of vascular endothelial growth factor and platelet-derived growth factor-C in aqueous humor with neovascular glaucoma (r = 0.346, p = 0.006). However, iris neovascularization grade and primary fundus disease were not significant elements in the expression level of vascular endothelial growth factor and platelet-derived growth factor-C. Higher concentrations of vascular endothelial growth factor and platelet-derived growth factor-C were found in aqueous humor of patients with neovascular glaucoma compared with control, which could be lowered by retinal photocoagulation to some extent. Platelet-derived growth factor-C inhibitors may be another potential target for ocular neovascular diseases.

Multiplex Cytokine Analysis of Aqueous Humor from the Patients with Chronic Primary Angle Closure Glaucoma

ABSTRACTPurpose: To compare the levels of cytokines and growth factor in aqueous humor of the patients with chronic primary angle closure glaucoma (PACG) and cataract.Methods: Aqueous humor samples were collected from 19 chronic PACG patients and compared with 14 nonglaucomatous controls presenting for cataract surgery. The levels of 27 cytokines and growth factors were measured in the aqueous samples using multiplex bead immunoassay and compared across groups.Results: Significantly higher levels of interleukin (IL)-8 (p < 0.001), eotaxin (p < 0.001), interferon gamma-induced protein (IP)-10 (p < 0.001) and macrophage inflammatory protein-1-beta (MIP-1β; p < 0.001) were observed in aqueous of chronic PACG patients compared to controls. In comparison to controls, significantly lower levels of IL-9 (p = 0.001), IL-17 (p < 0.001), tumor necrosis factor-alpha (TNF-α; p < 0.001), granulocyte–macrophage colony-stimulating factor (GM-CSF; p < 0.001), and IL-5 (p = 0.001) were observed in chronic PACG eyes. All other assayed cytokines—IL-1β, interleukin-1 receptor antagonist (IL-1rα), IL-6, IL-7, IL-10, IL-12, IL-13, IL-15, fibroblast growth factor-basic (FGF-basic), granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1-alpha (MIP-1α), and vascular endothelial growth factor (VEGF) —showed no significant difference between the groups.Conclusions: These results suggest that the aqueous cytokine levels of chronic PACG eyes differ significantly from nonglaucomatous eyes. This is the first study reporting significantly increased levels of eotaxin, MIP-1β, and IP-10 and lower levels of TNF-α, IL-5, IL-9, IL-17, and GM-CSF in chronic PACG patients, suggesting a plausible role of these inflammatory cytokines in its pathogenesis.

Clinical observation of concentration of vascular endothelial growth factor in aqueous humor after Conbercept intravitreal injection combined with oral use of traditional Chinese medicine——Tangwang kang for the treatment of diabetic retinopathy

Objective To observe the concentration of vascular endothelial growth factor in aqueous humor after Conbercept intravitreal injection combined with oral use of Chinese traditional medicine—Tangwangkang for the treatment of diabetic retinopathy (DR), and clinically evaluate the curative effect of this combined treatments. Methods The DR patients diagnosed from May 2013 to November 2014 were selected. Sixteen patients of treatment group received Conbercept intravitreal injection and paracentesis of anterior chamber combined with Tangwangkang capsule during the period of treatment, while other sixteen patients of control group only received Conbercept intravitreal injection and paracentesis of anterior chamber. The a queous humor of the patients of both groups were extracted respectively 4, 6, 8 and 12 weeks after intravitreal injection, and the concentration of VEGF in aqueous humor was measured using double antibody sandwich enzyme linked immunosorbent assay. The vision and the variations of fundus oculi were determined by follow-up examinations. Results The samples of aqueous humor of all 32 DR patients were collected. ⑴ Average concentration of VEGF in DR patients was(163.21±67.23) pg/ml before the treatment and 6 weeks after the treatment, the concentrations of VEGF in treatment and control group were(118.2±3.47) pg/ml and(128.13±6.21) pg/ml respectively.The differences between before and after the treatment in both two groups were statistically significant (P<0.05). ⑵ The differences between before and after the treatment in both two groups were statistically significant (treatment group t=4.365, P=0.031; control group t=4.723, P=0.028), and the difference between the two groups after the treatment was also statistically significant(t=0.362, P<0.05). ⑶ Both treatments significantly improved the fundus oculi and the differences between before and after the treatment were statistically significant(P<0.001), and the difference between the two groups was also statistically significant. (t=4.742, P<0.05). Conclusion Intravitreal injection can effectively ameliorate VEGF concentration inside of the eyes to cure DPDR. A combination of intravitreal injection and Tangwangkang capsule may reduce VEGF concentration of aqueous humor and consequently decrease the injection times of anti VEGF drugs, which may suggest that the acting pathway of Tangwangkang is consistent with that of anti VEGF drugs. Key words: Diabetic retinopathy; Injection, intravitreal; Paracentesis, anterior chamber; Tangwangkang

Expression of promyelocytic leukemia protein and vascular endothelial growth factor in aqueous humor and vitreous fluid in patients with proliferative diabetic retinopathy

AimsTo examine the expression of promyelocytic leukemia protein (PML) in the eye of proliferative diabetic retinopathy (PDR) patients. MethodsPML mRNA levels were measured in proliferative membranes from 12 PDR patients and idiopathic epiretinal membranes from 5 control patients by quantitative RT-PCR. Protein levels of PML and vascular endothelial growth factor (VEGF) in aqueous humor and vitreous fluid samples from 34 PDR patients and 38 control patients were determined using ELISA. ResultsThe PML mRNA expression levels in membrane samples, and the PML protein concentrations in aqueous humor and vitreous fluid samples were significantly lower in PDR patients than control patients. We observed a statistically significant inverse correlation between the concentrations of PML and VEGF in the aqueous humor and vitreous fluid of PDR patients. ConclusionPML may be a good candidate as a diagnostic marker and a therapeutic agent for PDR.

Increased levels of vascular endothelial growth factor in aqueous humor of patients with diabetic retinopathy: Is it the whole truth?

Increased levels of vascular endothelial growth factor in aqueous humor of patients with diabetic retinopathy: Is it the whole truth?

Level of Vascular Endothelial Growth Factor in Aqueous Humor and Surgical Results of Ahmed Glaucoma Valve Implantation in Patients With Neovascular Glaucoma

To determine the associations between the levels of growth factors in aqueous humor and the surgical outcomes of Ahmed glaucoma valve implantation in patients with neovascular glaucoma (NVG). From 19 NVG eyes of 19 patients, a sample of aqueous humor was taken just before Ahmed glaucoma valve implantation. Levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, and TGF-beta2 in aqueous humor aspirates were measured using a sandwich enzyme-linked immunosorbent assay method. When the postoperative intraocular pressures were >or=21 mm Hg with or without antiglaucoma medications at 2 successive visits or when any other surgical interventions were needed to lower intraocular pressure, that surgery was considered a failure. After patients were classified into success versus failure groups, the levels of the growth factors between the 2 groups was compared. The cumulative probability of success according to Kaplan-Meier analysis was also determined. Mean postoperative follow-up period was 40.9+/-19.6 months and cumulative probability of success was 43% at 57 months after surgery. Mean VEGF level in the failure group was higher than that of the success group (P=0.014). However, there was no statistical difference in the levels of TGF-beta1, TGF-beta2, and protein between 2 study groups (all P>0.05). The level of VEGF in aqueous humor was significantly higher in the failure group after the Ahmed glaucoma implantation compared with the success group. Our results imply that VEGF may play a role in determining surgical success after Ahmed valve implantation in patients with NVG.

Vascular Endothelial Growth Factor in Aqueous Humor Before and After Intravitreal Injection of Bevacizumab in Eyes With Diabetic Retinopathy

To study the concentration of vascular endothelial growth factor in the aqueous humor before and after intravitreal injection of bevacizumab in eyes with proliferative diabetic retinopathy. In this prospective, interventional case series, 1.25 mg of bevacizumab was injected into the vitreous cavity as preoperative adjunctive therapy 1 week before pars plana vitrectomy to treat proliferative diabetic retinopathy in 18 eyes in 18 patients. Aqueous humor samples were obtained just before intravitreal injection of bevacizumab and just before vitrectomy 1 week after the injection. Aqueous humor samples also were obtained in patients with cataract without diabetes mellitus (control group). The vascular endothelial growth factor concentration in the aqueous humor was measured using an enzyme-linked immunosorbent assay. Vascular endothelial growth factor concentration in the aqueous humor ranged from 146 to 676 pg/mL (mean +/- SD, 326 +/- 125 pg/mL) before intravitreal injection of bevacizumab and decreased to less than 31 pg/mL (P < .001) in all eyes 1 week after injection. Intravitreal bevacizumab therapy caused no adverse events. The concentrations in the control group ranged from 80 to 218 pg/mL (mean +/- SD, 146 +/- 40 pg/mL). Intravitreal injections of bevacizumab resulted in a substantial decrease in vascular endothelial growth factor in the aqueous humor.

Increased level of vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma

This study aimed to quantitate and compare the concentration of vascular endothelial growth factor (VEGF) in aqueous humor samples from patients with neovascular glaucoma (NVG), primary open-angle glaucoma (POAG), and cataract, as well as in serum samples of healthy human subjects. The authors collected aqueous humor samples by using their previously published technique of limbal paracentesis. The authors determined the concentration of VEGF by using a competitive enzyme immunoassay system and four-parameter logistic curve fitting and performed statistical analysis by using the Mann-Whitney-Wilcoxon test. The authors detected VEGF in 12 of 12 samples from patients with NVG (mean +/- standard error of the mean, 29.267 +/- 7.350 ng/ml), 15 of 28 samples from patients with POAG (0.726 +/- 0.204 ng/ml), 4 of 20 aqueous humor samples from patients with cataract (0.257 +/- 0.043 ng/ml), and 16 of 16 human serum samples (20.246 +/- 1.568 ng/ml). The mean concentration of VEGF in aqueous humor of patients with NVG was 40- and 113-fold higher than that in patients with POAG and cataract, respectively, and the difference was statistically significant (P < 0.01). The VEGF level in patients with POAG was elevated compared with that in patients with cataract (P < 0.05). Although the mean concentration of VEGF in aqueous humor of patients with NVG was approximately 1.45-fold higher than that in serum, the difference was not significant (P > 0.05). The authors' findings show that patients with NVG had a significantly increased level of VEGF in the aqueous humor and implicate VEGF as an important factor in the pathogenesis of intraocular neovascularization in these patients. The authors discuss the possible role of the ciliary epithelium, in addition to retina, in the production of VEGF and the complementary function of basic fibroblast growth factor and other growth factors.