Humor Vascular Endothelial Growth Factor Research Articles

Axial myopia, a protective factor for diabetic retinopathy-role of vascular endothelial growth factor.

Long axial length is one of the ocular protective factors in development of diabetic retinopathy (DR). In this study we examined the effect of axial length (AL) on aqueous humor vascular endothelial growth factor (VEGF) levels in patients with diabetes mellitus with or without DR. Forty-eight eyes of 48 participants were divided into three groups of 16 each. Group A consisted of non-diabetic patients, Group B had diabetic patients without DR, and Group C had diabetic patients with treatment-naive non-proliferative DR (NPDR). The groups were further subdivided based on axial lengths i.e., AL ≤ 23.30 mm (A1, B1, C1) and AL > 23.30 mm (A2, B2, C2). Undiluted aqueous humor was obtained during cataract surgery to measure the VEGF levels. We observed significant decrease in VEGF concentration in patients with AL ≥ 23.30 mm as compared with AL ≤ 23.30 mm in non-diabetic as well as diabetic patients. As the eye elongates, there is less secretion of VEGF in non-diabetics as well in diabetics with or without DR. Our findings strengthened the concept that an increase in AL leads to less VEGF in diabetic eyes, thus leading to less severe DR changes.

Effect of Probenecid on Endothelial Cell Growth Rate and Retinal Angiogenesis in an Oxygen-Induced Retinopathy Model.

Objectives: Probenecid is an anion transport inhibitor, which, according to the connectivity map (CMap; a biological application database), interferes with hypoxia-induced gene expression changes in retinal vascular endothelial cells (ECs). Here, we investigated the influence of probenecid on retinal EC cytotoxicity and retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model. Methods: The retinal EC growth rate in the presence of hypoxia-mimicking concentrations of cobalt chloride (CoCl2) was determined using the thiazolyl blue tetrazolium bromide (MTT) assay and proliferating cell nuclear antigen (PCNA) expression. In OIR rats, probenecid was administered by intraperitoneal injection (i.p.) from postnatal day (P) 1 to P7. The concentrations of vitreous humor vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α, and placental growth factor (PlGF) were determined by using the ELISA kit at P21. The amount of newly formed vascular lumen was evaluated by histopathological examination. Retinopathy and neovascularization were assessed by scoring isolectin B4 fluorescein–stained retinal flat mounts. Western blots for liver tissue HIF-1α and hepcidin (HAMP) were performed. Results: In vitro, probenecid led to the recession of the hypoxia-induced EC growth rate. In vivo, compared to the OIR retina, the upregulation of VEGF, HIF-1α, and PlGF in phase II retinopathy of prematurity (ROP) was inhibited by probenecid administration. Moreover, probenecid ameliorated neovascularization and resulted in significantly reduced relative leakage fluorescence signal intensity in fluorescein-stained retinal flat mounts (p < 0.05). Probenecid alleviated the liver overactivation of HAMP and downregulation of HIF-1α in OIR rats. Conclusions: This is the first demonstration that implies that probenecid might be a protective compound against retinal angiogenesis in OIR. These changes are accompanied with decreased hyperoxia-mediated hepcidin overproduction. Although the relevance of the results to ROP needs further research, these findings may help establish potential pharmacological targets based on the CMap database.

Aqueous humor vascular endothelial growth factor concentration before and after intravitreal injection of Bevacizumab for diabetic retinopathy

Aim: To study the concentration of aqueous humor vascular endothelial growth factor (VEGF) before and after intravitreal injection of Bevacizumab in eyes with proliferative diabetic retinopathy (PDR) and correlate this with area of retinal ischemia and neovascularization. Methods: In this prospective, interventional case series; 1.25 mg of Bevacizumab was injected into the vitreous cavity in 48 PDR eyes of 29 consecutive patients. Aqueous humor samples were obtained before intravitreal Bevacizumab injection and 1 week after, or before starting cataract surgery in the controls. The controls were 15 consecutive non-diabetic patients undergoing cataract surgery (15 eyes). Results: Aqueous VEGF level was higher in eyes with PDR than in control eyes (474.2 ± 361.3 vs. 120.65 ± 45.05 pg/mL) and this level reduced to 16.96 ± 18.1 pg/ mL 1 week after Bevacizumab injection (p<0.001). There was significant correlation between aqueous VEGF level and retinal ischemia-neovascularization area. No correlation between aqueous VEGF level and clinical markers such as blood glucose levels, HbA1C lever and duration of diabetes. Conclusion: VEGF levels correlate with the area of retinal ischemia and presence of neovascularization.

Relationships among Retinal Nonperfusion, Neovascularization, and Vascular Endothelial Growth Factor Levels in Quiescent Proliferative Diabetic Retinopathy.

Purpose: To investigate the relationships among the retinal nonperfusion (NP) area, neovascularization (NV) area, and aqueous humor vascular endothelial growth factor (VEGF) levels in quiescent proliferative diabetic retinopathy (PDR). Methods: Forty-seven eyes from 47 patients with treatment-naïve PDR that did not show macular edema or vitreous hemorrhage were enrolled. NP area, NV number, and NV area were quantitatively measured using ultra-widefield fluorescein angiography in an automated manner. Aqueous humor VEGF level was measured using a bead assay. Results: The NP areas of the total, posterior pole, peripheral retinae, and NV area positively correlated with each other (all p < 0.034). NV number correlated with total NP area, peripheral NP area, and NV area (all p ≤ 0.001). VEGF levels were significantly positively correlated with total, posterior polar, and peripheral NP areas and NV area (r = 0.575, 0.422, 0.558, and 0.362, respectively; all p ≤ 0.012). In eyes with NV in the disc area, the VEGF level was higher compare to eyes without NV in the disc area (208.89 ± 192.77 pg/mL vs. 103.34 ± 132.66, p = 0.010). A multiple linear regression model using NP area, NV area, and NVD demonstrated good prediction for VEGF level (R2 = 0.417, p < 0.001) and revealed a significant contribution of the peripheral NP area in predicting the VEGF level (β = 0.497, p = 0.002). Conclusions: Aqueous humor VEGF levels in quiescent PDR eyes were associated with NP and NV areas, which had positive correlations with each other. In addition, the NP area of the peripheral retina was the most important predictor of VEGF level.

The changes of aqueous humor vascular endothelial growth factor and pigment epithelium-derived factor levels before and after intravitreal injection of ranibizumab in proliferative diabetic retinopathy

Background Intraocular neovascularization is a primary cause of visual reduce in proliferative diabetic retinopathy (PDR), and intravitreal injection of ranibizumab is one of treating approachs.Researching the mechanism of intravitreal injection of ranibizumab for PDR is a new target for the prevention and management of PDR. Objective This study was to determine the levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of PDR eyes before and after intravitreal injection of ranibizumab. Methods Self-controlled observational study was designed.Fifteen eyes of 15 PDR patients with type 2 diabetes mellitus were included in Fuzhou General Hospital of Nanjing Military Command from January to August 2014, and 1 eye combined with neovascular glaucoma and iris rubeosis.Aqueous samples of 0.1 ml at each time were collected before and 7 days after the injection of ranibizumab from all patients under the informed consent.The changes of aqueous VEGF and PEDF concentrations were detected and analyzed by enzyme-linked immunosorbent assay.This study complied with Declaration of Helsinki and the protocol was approved by this hospital. Results The freeVEGF concentrations before and 7 days after intravitreal injection were (179.4±136.5) pg/ml and (27.1±23.5) pg/ml, respectively, showing a significant reduce after intravitreal injection of ranibizumab (t=4.172, P=0.001). PEDF concentrations before and 7 days after intravitreal injection were (394.0±237.2) pg/ml and (267.7±199.6) pg/ml, respectively, showing a significant reduce after intravitreal injection of ranibizumab (t=5.443, P=0.000). Intraocular neovascularization vanished after intravitreal injection of ranibizumab and vitrectomy was carried out at the seventh day after intravitreal injection. Conclusions Free VEGF and PEDF levels in aqueous humor appear to be significantly decreased after intravitreal injection of ranibizumab, and ocular neovascularization disappears at same time, which avoids intraoperative bleeding during vitrectomy. Key words: Angiogenic factor/aqueous humor; Angiostatic proteins/aqueous humor; Diabetic retinopathy; Neovascularization; Vascular endothelial growth factor; Pigment epithelium-derived factor; Enzyme-linked immunosorbent assay; Ranibizumab

Aqueous humor vascular endothelial growth factor in dogs: association with intraocular disease and the development of pre‐iridal fibrovascular membrane

To examine the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor of dogs with intraocular disease and to evaluate the association of aqueous humor VEGF with pre-iridal fibrovascular membrane (PIFM) formation. Two hundred and twenty six aqueous humor samples and 101 plasma samples were collected from 178 dogs with a variety of intraocular diseases (including cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation, and intraocular neoplasia), and aqueous humor was collected from 13 ophthalmically normal control dogs. Systemic disease status and administration of select medications were recorded. Aqueous and plasma VEGF was assayed via enzyme-linked immunosorbant assay validated for canine VEGF. Available histopathology samples were examined for the presence of PIFM. Where present, PIFMs were categorized as none, cellular, vascular or fibrous, and fibrovascular. Data were evaluated by mixed model anova, with application of Tukey-Kramer adjustment for multiple comparisons. There was no association between aqueous humor and plasma VEGF levels. Compared with normal controls, aqueous humor VEGF was significantly elevated for all intraocular diseases (P < 0.05) except for primary and diabetic cataracts. Systemic disease and administered medications had no significant effect on aqueous humor VEGF concentration. Compared to dogs without PIFM, aqueous humor VEGF was significantly higher in dogs with fibrovascular PIFM (P = 0.001), but not cellular (P = 0.1704) or fibrous/vascular PIFM (P = 0.0667). These findings confirm that VEGF is commonly elevated in aqueous humor of dogs with intraocular disease and likely plays a role in the causation or progression of a variety of intraocular disorders, including the development of PIFM.

Aqueous humor and plasma vascular endothelial growth factor in uveitis-associated cystoid macular edema

PURPOSE: To determine the association between cystoid macular edema and vascular endothelial growth factor concentration in the aqueous humor and plasma of uveitis patients. METHODS: Cross-sectional study. Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay in the aqueous humor of 20 uveitis patients (9 with and 11 without cystoid macular edema), and in the plasma of 40 uveitis patients (20 with and 20 without cystoid macular edema) and 20 healthy volunteers. RESULTS: Mean aqueous humor vascular endothelial growth factor concentrations for uveitis patients with and without cystoid macular edema were 152.3 and 109.5 pg/ml, respectively, P = .044. Mean plasma vascular endothelial growth factor concentrations in uveitis patients with and without cystoid macular edema and in healthy volunteers were 32.2, 29.6, and 55.0 pg/ml, respectively. Uveitis patients had lower plasma vascular endothelial growth factor levels than did healthy volunteers, P = .0002 CONCLUSION: In uveitis patients, vascular endothelial growth factor concentration is increased in the aqueous humor of eyes with cystoid macular edema. It may be useful to investigate vascular endothelial growth factor antagonists as a treatment for uveitis-associated cystoid macular edema.