Vitreous Fluid Of Patients Research Articles

Role of chemokines in diabetic retinopathy

SummaryWe have detected altered expression of chemokines in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR). In the early phase of disease chemokines (CXCL8, CCL2) are involved in leukocyte attraction. Later, CXCL12 may attract progenitor cells (endothelial cell precursors and fibrocytes) involved in establishment of neovessels and in formation of fibrovascular membranes. The myofibroblasts producing ECM in the fibrovascular membranes of the diabetic patients can originate from endothelial (precursor) cells via endoMT, from fibrocytes or from leukocyte‐like precursors. During the active disease stage also angiostatic chemokines (CXCL4, CXCL4L1 and CXCL10) are upregulated, probably in an attempt to counteract the stimulatory effects (angiogenesis and increased vascular permeability) of VEGF. Finally, CCL2 and CXCL10 have been reported to induce fibrosis and might play a role in the later stages of the pathology. Recently, we have demonstrated that CXCL4L1, a most potent angiostatic chemokine can be applied therapeutically as VEGF‐inhibitor in diabetic rats. Indeed, intraocular injections of CXCL4L1 early after the onset of diabetes protected animals against diabetes‐induced blood‐retinal barrier breakdown.

Short Communication: Increase of Sialylated N-Glycansin Eyes with Neovascular Glaucoma Secondary to Proliferative Diabetic Retinopathy

Purpose: To investigate the alteration of N-glycans in the vitreous fluid of patients with neovascular glaucoma (NVG) secondary to proliferative diabetic retinopathy (PDR).Methods: Vitreous samples were collected from 18 patients with PDR (including 7 with NVG and 11 without NVG), and 17 patients without diabetes. Profiles of N-glycans were analyzed by glycoblotting-based high throughput protocol, which we recently developed. Protein levels of vascular endothelial growth factor (VEGF)-A were measured by ELISA.Results: The concentration of total N-glycans and the concentration of N-glycans with sialic acids were significantly higher in NVG group compared with those in non-NVG group or control group, whereas there was no significant difference in concentrations of high-mannose N-glycans among three groups. There was a moderate correlation between the concentrations of sialylated N-glycans and VEGF-A.Conclusions: Our data demonstrate the distinct changes of N-glycan profile and the increase of sialylated N-glycans in eyes with NVG secondary to PDR.

CD18 expression in granulocytes infiltrating the vitreous fluid in patients with diabetic retinopathy.

To assess the levels of CD18 on the surface of granulocytes infiltrating the vitreous fluid in patients with diabetic retinopathy (DR). Vitreous samples from twelve patients with non-proliferative DR with significant macula edema (group A), 33 patients with proliferative DR (grade 3 as group B, n=14, and, grade 4 as group C, n=19) were obtained during pars plana vitrectomy. Vitreous samples from 12 patients with macular hole as controls (group D) were analyzed together. The infiltrating of granulocytes and its surface level of CD18 were measured by flow cytometry. The level of CD18 was presented as the mean channel fluorescence (MCF) on a logarithmic scale. Granulocytes were detected in 6 of 12 vitreous samples from group A, 9 of 14 from group B, 15 of 19 from group C, and none of 12 from group D. MCF of CD18 on granulocytes from groups A, B, and C were 2.978±1.446, 3.201±0.692, and 4.072±0.837, respectively. The difference was significant (F=4.354, P=0.021). Subjects with more severe DR were more likely to have a higher level of CD18 MCF (trend test, χ (2)=7.351, P=0.007). CD18 MCF was significantly associated with the development of DR (r=0.46, P=0.005 and β=0.147, P=0.035). Our results confirm the presence of granulocytes and the elevated levels of CD18 on the surface of them in the vitreous fluid from DR patients. These results may provide indirect evidence shown that granulocytes activation also has occurred in the retinal local compared to non-DR control.

The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy

Proteins in the vitreous play an important role on the induction of proliferative vitreoretinopathy (PVR) after retinal detachment. The aim of this study was to investigate the variation of protein patterns in the vitreous of PVR eyes and examine whether differentially expressed protein levels were expressed in experimental PVR retina. Vitreous samples from PVR and macular hole patients were selected for proteomic analysis. The vitreous protein samples were separated by two-dimensional electrophoresis (2-DE). The differentially expressed protein spots in the two groups were excised and subjected to in-gel digestion and identification by electrospray ionization mass spectrometry (ESI-MS) analysis. Two differentially expressed proteins, zinc finger protein 670 (ZFP 670) and prostaglandin D2 synthase (PGD2S), were further validated by immunohistochemical staining and western blotting analysis in the retina of the experimental rabbit PVR model. In proteome analysis of human vitreous samples, five proteins had increased expression in PVR, including zinc finger protein 670 (ZFP 670), prostaglandin D2 synthase (PGD2S), IgG (Immunoglobulin G) light chain, transthyretin precursor, and haptoglobin precursor. ZFP 670 and PGD2S levels were expressed significantly higher in the experimental PVR retinas than in the control group. Levels of ZFP 670 and PGD2S were elevated in the vitreous fluid of patients with PVR. In addition, there were higher expressions of ZFP 670 and PGD2S in the experimental PVR retina. This result will expand our knowledge of pathophysiologic characteristics of PVR, and might be helpful for further developing possible treatment on this disorder.

The role of erythropoietin in physiological angiogenesis of the mouse retina

Background: Diabetic retinopathy (DR) is a prevalent microvascular complication and it is characterized by increased vascular permeability, ischemia and neovascularization. Angiogenesis is modulated by growth factors such as vascular endothelial growth factor and angiopoietin-2. Recently, it is found that erythropoietin, besides neuroprotection, has angiogenic effects and its level is highly elevated in vitreous fluid of patients with proliferative diabetic retinopathy. However, the role of erythropoietin in physiological angiogenesis of the retina and its cooperation with angiopoietin 2 remains unclear.

Detection of choroid- and retina-antigen reactive CD8+ and CD4+ T lymphocytes in the vitreous fluid of patients with birdshot chorioretinopathy

Birdshot chorioretinopathy (BSCR), a progressive form of non-infectious uveitis, is the strongest HLA-associated disease described to date, with >95% of the patients displaying HLA-A29. Since indirect evidence indicates the involvement of T cells in the etiopathology of the disease, we now isolated, cultured and analyzed the vitreous fluid-infiltrating T cells from two BSCR patients with respect to their phenotype, cytokine profile, clonal distribution and antigen specificity. Phenotypic analyses revealed the predominant presence of both CD4+ and CD8+ T cells in vitreous fluid. Further analyses on short term expanded and cloned T cells suggested that eye-infiltrating T cells generally displayed a Th1 like cytokine profile with secretion of high levels of IFN-γ and TNF-α. In one patient an oligoclonal CD4+ and CD8+ T cell infiltration, with a moderate to strongly skewed TCR Vβ usage was suggestive for an antigen driven infiltration/expansion. Indeed, a number of intraocular CD4+ and CD8+ T cells responded to crude retinal and choroidal lysates. These results, which demonstrate for the first time the existence of eye-antigen-specific T cells in the vitreous fluid of BSCR patients, substantiate the current view on the role of eye-antigen specific T cells in the etiopathology of BSCR.

Current and future management of diabetic retinopathy: a personalized evidence-based approach.

Diabetic retinopathy (DR) is the leading cause of new-onset blindness in working-age individuals in the USA and represents a growing worldwide epidemic. Classic risk factors for onset or progression of DR include poor glycemic control, hypertension and hyperlipidemia; however, these factors account for only a small proportion of the risk of DR. New systemic risk factors are emerging, which may allow for personalized risk profiling and targeted treatment by physicians. In addition, early studies of vitreous fluid in patients with DR have resulted in a new paradigm: diabetes causes inflammation in the retina, which is mediated by multiple small signaling molecules that induce angiogenesis and vascular permeability. Future treatment of DR may involve two approaches: early vitreous analysis, followed by drug treatment targeted to the unique vitreous composition of the patient; and collaboration between ophthalmologists and primary care providers to address the unique systemic risk profile of each diabetic patient.

Identification of new pathogenic candidates for diabetic macular edema using fluorescence‐based difference gel electrophoresis analysis

Diabetic macular edema is the main cause of visual impairment in diabetic patients. The aim of the present study was to explore the differential proteomic pattern of the vitreous fluid from diabetic macular edema patients by means of fluorescence-based difference gel electrophoresis (DIGE). Samples of vitreous from eight type 2 diabetic patients [four with diabetic macular edema without proliferative diabetic retinopathy and four with proliferative diabetic retinopathy without diabetic macular edema), and eight from non-diabetic subjects with idiopathic macular hole (control group) were selected from our vitreous bank for proteomic analysis. To further confirm the potential candidates identified by DIGE, 18 additional samples (six proliferative diabetic retinopathy, six diabetic macular edema and six macular hole, matched by age) were analysed by enzyme-linked immuno sorbent assay (ELISA). Selecting an abundance ratio of 1.5-fold, p < 0.05, as the threshold for the study, four proteins were specifically associated with diabetic macular edema. Hemopexin was significantly higher in the vitreous fluid of patients with diabetic macular edema in comparison with both control subjects and proliferative diabetic retinopathy patients. By contrast, clusterin, transthyretin and crystallin S were significantly decreased in the vitreous of patients with diabetic macular edema. The differential production of hemopexin, clusterin and transthyretin was further confirmed by ELISA. Proteomic analysis by DIGE was useful in identifying new potential candidates involved in the pathogenesis of diabetic macular edema. These results could open up new strategies in the treatment of diabetic macular edema.

Correlation of inflammatory and proangiogenic cytokines from undiluted vitreous samples with spectral domain OCT scans, in untreated branch retinal vein occlusion

PurposeTo assess the levels of inflammatory and angiogenic cytokines in undiluted vitreous from treatment-naïve patients with macular edema secondary to nonischemic branch retinal vein occlusion (BRVO), with flow cytometric bead array (CBA) and to correlate the results with subjective and multiple spectral-domain optical coherence tomography (SD-OCT) parameters.MethodsA total of 43 eyes from 43 patients (mean age 69.7 years, 23 male) were divided into groups of new, “fresh” (n = 28; mean duration after onset 4.1 months) and older BRVO (n = 15; 11.6 months). Because of macular edema, these patients underwent an intravitreal therapy combining a single-site 23 g core vitrectomy with bevacizumab and dexamethasone. Undiluted vitreous was then analyzed for interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor isoform A (VEGF-A) levels with CBA and correlated with visual acuity (VA), clinical parameters of BRVO (type and perfusion status), and morphologic parameters, such as central macular thickness, central retinal thickness, thickness of the neurosensory retina, thickness of the serous retinal detachment, and the disruption of the ellipsoid line (photoreceptor inner and outer segments) and the external limiting membrane, as measured with SD-OCT. Twenty-eight undiluted vitreous samples from patients with idiopathic, nonuveitis vitreous floaters served as the controls.ResultsThe mean IL-6 was 23.2 pg/mL (standard deviation, ±48.8), MCP-1 was 602.6 (±490.3), and VEGF-A was 161.8 (±314.3), and this was higher than in the control group, which had a mean IL-6 of 6.2 ± 3.4 pg/mL (P = 0.17), MCP-1 of 253.2 ± 73.5 (P < 0.0000001), and VEGF-A of 7.0 ± 4.9 (P < 0.003). In all BRVO samples, IL-6 correlated positively with MCP-1 and VEGF-A (correlation coefficient r = 0.79 and r = 0.46, respectively). VEGF-A was the only cytokine to correlate significantly with SD-OCT parameters (thickness of the neurosensory retina r = 0.31; disruption of the ellipsoid line r = 0.33). In the older BRVO group, there was a positive correlation between cytokines (IL-6 with MCP-1, r = 0.77; Il-6 with VEGF-A, r = 0.68; MCP-1 and VEGF-A, r = 0.68), whereas only IL-6 correlated with MCP-1 in the fresh group (r = 0.8).ConclusionThe inflammatory markers and VEGF-A were elevated in the vitreous fluid of patients with BRVO, and these correlated with one another. VEGF-A was more often correlated with the morphologic changes assessed by SD-OCT, whereas the inflammatory markers had no significant influence on SD-OCT changes.

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.

Clinical Evidence of Sustained Chronic Inflammatory Reaction in Retinitis Pigmentosa

To study the nature of inflammatory reaction in eyes of patients with retinitis pigmentosa (RP) and its possible role in the pathogenesis of RP. Retrospective, observational study. Three hundred seventy-one consecutive patients diagnosed with typical RP were included in this study. We included 165 patients without active inflammatory diseases, including 20 patients diagnosed with cataract, and 36 patients diagnosed with idiopathic epiretinal membrane as controls. Density of the inflammatory cells in the anterior vitreous cavity was measured and graded by slit-lamp biomicroscopy. A multiplex enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of cytokines and chemokines in aqueous humor and vitreous fluid of patients with RP and controls. In addition, we investigated the relationship between visual function and anterior vitreous cells in these patients. Slit-lamp biomicroscopic analysis, best-corrected visual acuity, visual field analysis, and multiplex ELISA. In 190 of 509 eyes with RP (37.3%), "1+" (5-9 cells per field) or more cells were observed in the anterior vitreous cavity. Strong inflammatory reaction with "2+" cells (10-30 cells per field) was associated with younger age. In the elderly patients with RP, significantly decreased visual function was seen in a group with "1+" or more cells (P<0.05). Moreover, the levels of a variety of proinflammatory cytokines and chemokines, including monocyte chemotactic protein-1, were increased both in the aqueous humor and vitreous fluid of RP patients compared with the levels in control patients. Sustained chronic inflammatory reaction may underlie the pathogenesis of RP, suggesting interventions for ocular inflammatory reaction as a potential treatment for patients with RP. The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Vitreous levels of somatostatin in patients with chronic uveitic macular oedema

Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. χ(2)-square test, Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. Plasma SST concentrations were similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22-29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38 mg/ml vs 0.73±0.32 mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73 pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (ρ=0.191, P=0.57 and ρ=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (ρ=0.302, P=0.31 and ρ=0.45, P=0.13). Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.

Soluble Vascular Adhesion Protein-1 Accumulates in Proliferative Diabetic Retinopathy

Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells. Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells. Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells. Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.

Simultaneous Analysis of Multiple Cytokines in the Vitreous of Patients with Sarcoid Uveitis

Levels of some cytokines are significantly higher in the vitreous fluid of patients with acute uveitis than in normal vitreous fluid. The authors sought to determine which proinflammatory cytokines were upregulated in the vitreous fluid of patients with ocular sarcoidosis. Samples of vitreous fluid were collected from patients with sarcoid uveitis and from nonsarcoid control patients with idiopathic epiretinal membrane. The levels of 27 proinflammatory cytokines were measured with a multiplex beads array system. Postvitrectomy macular thickness was also measured by using spectral domain optical coherence tomography (SD-OCT). To assess the relationship between cytokine levels and disease stage, the authors divided patients into three groups based on macular thickness 1 month after operation. The vitreous levels of 17 cytokines were significantly higher in patients with ocular sarcoidosis than in nonsarcoid controls. Serum levels of interferon γ-induced protein 10 (IP-10) were also higher in ocular sarcoidosis patients than in nonsarcoid controls. Conversely, serum levels of interleukin (IL) 15 in ocular sarcoidosis patients were lower than in the control group. Analysis of cytokine levels and macular thickness revealed that IL-1ra, IL-4, IL-8, IFN-γ, IP-10, monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β, and regulated on activation, normal T-cell expressed and secreted (RANTES) were significantly upregulated in patients with thin cystoid macular edema group. Patients with ocular sarcoidosis had elevated levels of proinflammatory cytokines in vitreous fluids. Different cytokines might contribute to different stages of macular edema.

Succinate Increases in the Vitreous Fluid of Patients With Active Proliferative Diabetic Retinopathy

To examine vitreous succinate levels from proliferative diabetic retinopathy (PDR) patients and ascertain their association with PDR activity. Comparative case series. A total of 81 eyes of 72 PDR patients were divided into active PDR (22 eyes), quiescent PDR (21 eyes), and active PDR with intravitreal bevacizumab injection (38 eyes). Twenty epiretinal membrane (ERM) patients (21 eyes) served as controls. Mean vitreous succinate levels were 1.27 μM in ERM and 2.20 μM in PDR, with the differences statistically significant (P = .03). When comparing mean vitreous succinate levels (active PDR: 3.32 μM; quiescent PDR: 1.02 μM; active PDR with intravitreal bevacizumab injection: 1.20 μM), significant differences were found between active and quiescent PDR (P < .01) and between active PDR and active PDR with intravitreal bevacizumab injection (P < .01). Even though succinate levels were low, retinopathy activities were very high in patients with active PDR with intravitreal bevacizumab injection. Mean vitreous vascular endothelial growth factor (VEGF) levels (active PDR: 1696 pg/mL; quiescent PDR: 110 pg/mL; active PDR with intravitreal bevacizumab injection: n.d.) were similar to previous reports. Mean vitreous erythropoietin levels (active PDR: 703 mIU/mL; quiescent PDR: 305 mIU/mL; active PDR with intravitreal bevacizumab injection: 1562 mIU/mL) suggested very high retinopathy activities in patients with active PDR with intravitreal bevacizumab injection. Succinate, like VEGF, may be an angiogenic factor that is induced by ischemia in PDR. Although succinate is reported to promote VEGF expression, VEGF inhibition decreases succinate. Thus, VEGF, via a positive feedback mechanism, may regulate succinate.

Vascular Endothelial Growth Factor in Plasma and Vitreous Fluid of Patients with Proliferative Diabetic Retinopathy Patients after Intravitreal Injection of Bevacizumab

To investigate plasma and vitreous vascular endothelial growth factor (VEGF) levels after intravitreal bevacizumab (IVB) injection into eyes with proliferative diabetic retinopathy (PDR). Retrospective, interventional, nonrandomized, comparative study. Fifty-six eyes of 56 patients with PDR and 13 eyes of 13 patients with nondiabetic ocular diseases were enrolled. Analysis included evaluation of basic clinical conditions and measurement of vitreous and plasma VEGF concentrations using enzyme-linked immunosorbent assays. PDR eyes without IVB had the highest vitreous VEGF levels; the levels were significant compared with those in the recent IVB group (previous injection within 1 week), the prolonged IVB group (injection more than 1 week previously), and the nondiabetic control group (P = .001, P = .035, P < .001, respectively). The vitreous VEGF level in the recent IVB group was higher than that in prolonged IVB group (P = .035). PDR eyes without IVB had the highest plasma VEGF level, and the level was significant compared with those in the recent IVB group, the prolonged IVB group, and the nondiabetic control group (P < .001, P = .003, P < .001, respectively). The plasma VEGF level in the recent IVB group was lower than that in the prolonged IVB group (P = .003). The vitreous VEGF level was associated significantly with the plasma VEGF level (P = .002). Vitreous and plasma VEGF levels were increased markedly in patients with PDR. VEGF concentrations in vitreous and plasma were decreased significantly after IVB into PDR eyes, and the effect lasted from 4.4 ± 2.2 days to 34.8 ± 33.7 days after injection.

Correlation between Ficolin-3 and Vascular Endothelial Growth Factor-to-Pigment Epithelium-Derived Factor Ratio in the Vitreous of Eyes with Proliferative Diabetic Retinopathy

To investigate the relationship of ficolin-3 with inflammatory and angiogenic factors, namely, vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF), in the vitreous of eyes with proliferative diabetic retinopathy (PDR). Case-control study. Vitreous fluid and serum samples were obtained at the time of vitreoretinal surgery from 21 eyes of 21 patients with PDR and from 16 eyes of 16 nondiabetic patients with idiopathic macular hole. Ficolin-3, VEGF, and PEDF concentrations were determined by enzyme-linked immunosorbent assay. Vitreous ficolin-3 levels were significantly higher in eyes with PDR than in eyes with idiopathic macular hole. Similarly, VEGF levels also were significantly higher in eyes with PDR than in eyes with idiopathic macular hole. In contrast, vitreous PEDF concentrations were significantly lower in eyes with PDR than in eyes with idiopathic macular hole, and the VEGF-to-PEDF ratio was higher in eyes with PDR than in eyes with idiopathic macular hole. Furthermore, a significant correlation between ficolin-3 and the VEGF-to-PEDF ratio was observed in the vitreous of eyes with PDR. In addition, serum ficolin-3 levels in eyes with PDR were higher than the levels in eyes with idiopathic macular hole, and the vitreous ficolin-3 levels also correlated with serum ficolin-3 levels. We found that ficolin-3 levels were elevated in the vitreous fluid of patients with PDR. Our results suggest that ficolin-3 may be used as a new therapeutic target for treatment of PDR.

Role of soluble vascular endothelial growth factor receptor-2 in macular oedema with central retinal vein occlusion

Background and aimsTo measure soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) in the vitreous fluid of patients with central retinal vein occlusion (CRVO) and macular oedema or patients with idiopathic...

LIPOPOLYSACCHARIDE-BINDING PROTEIN AND SOLUBLE CD14 IN THE VITREOUS FLUID OF PATIENTS WITH PROLIFERATIVE DIABETIC RETINOPATHY

The purpose of this study was to compare intravitreous levels of lipopolysaccharide-binding protein and soluble CD14 (sCD14) between patients with proliferative diabetic retinopathy (PDR) and nondiabetic subjects. This study included 19 consecutive Type 2 diabetic patients with PDR in whom a vitrectomy was performed. Sixteen vitreous humors from nondiabetic patients matched by age, with idiopathic macular holes, were selected from our vitreous bank and used as a control group. Lipopolysaccharide-binding protein was assessed by enzyme-linked immunosorbent assay and sCD14 by a solid-phase enzyme-amplified sensitive immunoassay. Lipopolysaccharide-binding protein and sCD14 levels were significantly higher in patients with PDR than in the control group (lipopolysaccharide-binding protein, P < 0.001; sCD14, P < 0.01). After correcting for vitreal proteins, the results remained significantly higher in patients with PDR. No differences in serum levels were observed, and we did not find any correlation between serum and vitreous levels. A direct correlation between lipopolysaccharide-binding protein and sCD14 was detected in the vitreous fluid (r = 0.57; P < 0.001) but not in the plasma. Finally, a significant correlation between intravitreal levels of both lipopolysaccharide-binding protein and sCD14 and interleukin-8 and monocyte chemotactic protein-1 was also detected. Lipopolysaccharide-binding protein and sCD14 are elevated in the vitreous fluid of patients with PDR and thus may play a role in the innate immune response triggered by the inflammatory injury characteristic of PDR.

Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion

To investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs). Retrospective case-control study. Nineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group). Macular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time of vitreoretinal surgery. IL-8 and MCP-1 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Variables were compared with the Mann-Whitney U-test, Wilcoxon's signed-ranked test, and the chi2-test, when appropriate. To examine correlations, Spearman's rank-order correlation coefficients were calculated. Statistical significance was set at P<0.05. The vitreous fluid levels of IL-8 (median: 63.5 pg/ml) and MCP-1 (median: 1522.4 pg/ml) were significantly higher in the patients with BRVO than in the control group (median: 5.1 and 746.5 pg/ml respectively; P<0.001 and <0.001 respectively). Vitreous IL-8 and MCP-1 were significantly correlated in patients with BRVO (P=0.009). Both IL-8 and MCP-1 were elevated in the vitreous fluid of patients with BRVO and macular oedema. Both chemokines may contribute to the pathogenesis of macular oedema in patients with BRVO.