Vitreous Of Patients Research Articles

Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma.

Diagnosis of primary central nervous system lymphoma (PCNSL) is usually made by identifying malignant lymphocytes in the brain, cerebrospinal fluid (CSF), or vitreous. However, these cells are few and friable, and misdiagnosis can occur, even in properly prepared specimens. Recent data suggest that levels of interleukin 10 (IL-10) are elevated in the serum and vitreous of patients with non-Hodgkin lymphoma; levels of interleukin 6 (IL-6) are elevated in the vitreous of patients with intraocular inflammation unrelated to a malignant neoplasm. We investigated whether PCNSL involving the vitreous or CSF is associated with elevated ratios of IL-10 to IL-6. Vitreous specimens were obtained from 5 patients with PCNSL involving the eye and from 13 control patients with intraocular inflammation not related to a malignant neoplasm; CSF specimens were obtained from 11 patients with PCNSL. Levels of IL-10 exceeded those of IL-6 in all 5 patients with intraocular lymphoma but in none of the 13 patients with uveitis (P < .001). In patients with PCNSL, levels of IL-10 exceeded those of IL-6 in 6 of 11 CSF samples with malignant cells compared with 7 of 53 samples without malignant cells (P = .01). The calculated odds ratio (OR) suggests that the risk for malignant involvement of the CSF is about 8 times higher when IL-10 levels exceed IL-6 levels. Levels of IL-10 and IL-6 were determined by enzyme-linked immunosorbent assay in both vitreous and CSF specimens. The occurrence of PCNSL in the eye was strongly associated with elevated vitreous levels of IL-10 relative to levels of IL-6. Moreover, among patients with diagnosed PCNSL, malignant cells were significantly more likely to be present in CSF when levels of IL-10 exceeded those of IL-6.

Advanced Glycation End Products Induce Expression of Vascular Endothelial Growth Factor by Retinal Müller Cells

Recent studies have suggested that advanced glycation end products (AGEs) are involved in the development of diabetic complications. To assess the pathogenic role of AGEs and vascular endothelial growth factor (VEGF) in the development of retinal neovascularization in diabetic retinopathy, we investigated the effect of AGEs on induction of VEGF by retinal Müller cells and measured AGE and VEGF concentrations in the vitreous of patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the production of VEGF protein by cultured Müller cells were enhanced by the presence of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in patients with PDR compared with patients without diabetes (P< 0.01). There was a moderate positive correlation between the levels of crossline and VEGF (r=0.698,P< 0.01). Elevation of AGEs in the vitreous may promote intraocular neovascularization in diabetic retinopathy through production of VEGF from Müller cells.

Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation.

Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. Subretinal neovascularisation is an important cause of central visual loss, but little is known about the role of this growth factor in its pathogenesis. The aim of this study was to investigate the possible role of VEGF in the development of subretinal neovascularisation. Undiluted vitreous samples were obtained from patients undergoing vitrectomy for removal of non-age-related subfoveal neovascular membranes (SFNM). For comparison vitreous from patients undergoing vitrectomy for idiopathic full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR) was used. Indirect enzyme linked immunosorbent assay (ELISA), with an antibody directed against the conserved N-terminal region of human VEGF165, was used to determine vitreous levels of VEGF. The growth factor was also localised in the vitreous of patients with SFNM by western blot analysis. The mean (SE) VEGF concentration in the vitreous of patients with SFNM was 27.78 (2.22) ng/ml (n = 8), FTMH was 16.62 (0.9) ng/ml (n = 18), and PDR was 37.77 (3.28) ng/ml (n = 16). The differences between the PDR group and SFNM group versus the FTMH group were both significant (p = 0.0001 and p = 0.0015) as analysed by the Wilcoxon rank sum test). Vitreous levels of VEGF are significantly elevated in eyes with non-age-related subretinal neovascularisation compared with eyes with FTMH but not as elevated as in PDR. This suggests that VEGF is involved in subretinal angiogenesis.

Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.

Vascular endothelial growth factor (VEGF) is a hypoxia induced angiogenic factor. Recent studies have shown that high levels of VEGF accumulate in the vitreous of patients with proliferative diabetic retinopathy (PDR). The purpose of the present study was to identify the retinal cells that upregulate VEGF expression in human PDR patients representing progressive stages of retina deterioration. Thirteen formalin fixed and paraffin embedded enucleated eyes with PDR were used (eyes were enucleated because of being blind and painful as a result of neovascular glaucoma). Thin retina sections were hybridised in situ with a VEGF specific probe, to identify cells producing VEGF mRNA. All eyes with PDR showed upregulated expression of VEGF mRNA, specifically in the cells of the neurosensory retina. VEGF expression was upregulated in all three nuclear layers--namely, the ganglion cell layer, the inner nuclear layer, and the outer nuclear layer. However, in each patient, VEGF producing cells were mostly distributed in a different layer, or even confined to a specific region in that layer. For example, expression by the outer nuclear layer was mostly detected in detached (presumably hypoxic) regions of the retina. Progression of PDR is distinguished by a sustained, upregulated expression of VEGF by the neurosensory retina. Cells in all retina layers can potentially contribute to augmented VEGF production. The restricted population of VEGF producing cells in each case is likely to represent cells residing in ischaemic regions of the retina. Thus, VEGF may function as a linking factor between retinal ischaemia and PDR associated neovascularisation.

Posterior Vitreoschisis: An Echographic Finding in Proliferative Diabetic Retinopathy

To describe the echographic characteristics of splitting the outer posterior cortical vitreous in patients with proliferative diabetic retinopathy and vitreous hemorrhage. The authors retrospectively reviewed the echographic findings in 270 patients who were evaluated at the Doheny Eye Institute between January 1983 to December 1989 for proliferative diabetic retinopathy and vitreous hemorrhage. None of the eyes had undergone pars plana vitrectomy before echographic examination. Forty-five patients (17%) had echographic evidence of splitting of the outer posterior vitreous cortex, a finding the authors have termed posterior vitreoschisis. In all patients, differentiation of the posterior vitreoschisis from a true posterior hyaloid detachment was possible, either on the initial or on serial echographic examination, by the separate detachment of the inner wall of the vitreoschisis cavity and the true posterior hyaloid from the retinal surface. The vitreoschisis cavities often were found to contain unclotted blood. In some eyes, the inner wall of the vitreoschisis cavity was adherent to the apex of the most highly elevated area of traction retinal detachment, suggesting that posterior vitreoschisis may itself result in clinically significant vitreoretinal traction, independent of the presence or extent of true posterior hyaloid separation. The authors' finding suggest that spontaneous splitting of the outer posterior vitreous cortex may occur in patients with proliferative diabetic retinopathy and vitreous hemorrhage, which may mimic a true posterior cortical vitreous detachment on echographic examination. Preoperative recognition of posterior vitreoschisis may be important in the surgical management of these patients.

Interleukin-10 in the Vitreous of Patients With Primary Intraocular Lymphoma

To find an accurate and simple method to diagnose primary intraocular lymphoma. We prospectively analyzed concentrations of interleukin-10, interleukin-1, interleukin-2, interleukin-4, and interleukin-6 in vitrectomy specimens from three patients with primary intraocular lymphoma and five patients with uveitis by enzyme-linked immunosorbent assay. Interleukin-10 in the vitreous was detected in patients with primary intraocular lymphoma. Interleukin-10 levels correlated with clinical activity and the number of malignant cells. Concentrations of interleukin-10 in the vitreous may be a helpful clue to both clinicians and pathologists in diagnosing primary intraocular lymphoma.

Cytokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy.

We determined whether interleukin-8, monocyte chemotactic protein-1, and macrophage-colony stimulating factor are present in the vitreous of patients with proliferative diabetic retinopathy (PDR) or proliferative vitreoretinopathy (PVR). The levels of these cytokines were measured by specific enzyme-linked immunoassays in vitreous from 30 patients with PDR, 13 patients with PVR, and 26 control individuals, including 10 cadaver eyes and 16 patients with idiopathic macular holes, idiopathic macular puckers, vitreous hemorrhages, or uncomplicated retinal detachments. Detectable levels of interleukin-8 were found in 90% of vitreous samples of patients with PDR, 85% with PVR, and 58% of control samples. IL-8 was significantly increased in PDR (mean +/- SEM; 25.0 +/- 5.3 ng/ml; p = 0.01), but not in PVR (11.9 +/- 3.9 ng/ml; p = 0.50) compared to control human vitreous (8.5 +/- 2.5 2.5 ng/ml). MCP-1 was detected in 90% of vitreous samples of patients with PDR, 92% with PVR, and 81% of control samples. MCP-1 was significantly increased in PDR (6.2 +/- 0.9 ng/ml, p = 0.001) and PVR (7.7 +/- 2.5 ng/ml, p = 0.001) over the levels in control vitreous (1.2 +/- 0.2 ng/ml). M-CSF was detected in 94% of vitreous samples of patients with PDR, 88% with PVR, and 92% from control vitreous. M-CSF was significantly elevated in PDR (32.3 +/- 8.3 ng/ml, p = 0.03), but not in PVR (23.6 +/- 12.8 ng/ml, p = 0.4) compared to control (10.7 +/- 3.5 ng/ml). Our results suggest that IL-8, MCP-1, and M-CSF participate in the pathogenesis of PDR and PVR.

Cells of the Immune System and Their Cytokines in Epiretinal Membranes and in the Vitreous of Patients with Proliferative Diabetic Retinopathy

In the present study, we specifically investigated the presence of the main immune cells, namely T helper/inducer lymphocytes, T suppressor/cytotoxic lymphocytes, B lymphocytes and macrophages, for HLA-DR antigen expression and the cytokines IL-1 alpha and IL-2 in epiretinal membranes of proliferative diabetic retinopathy (PDR) using immunohistochemical staining. The levels of the two cytokines (IL-1 alpha and IL-2) in the vitreous were measured by ELISA. The results show that 18 out of the 32 epiretinal specimens reacted positively with monoclonal anti-CD4 (marker for T helper/inducer cell subset) antibody (56%), 21 reacted with monoclonal anti-CD8 (marker for T suppressor/cytotoxic subset) antibody (66%), 15 reacted with monoclonal anti-CD22 (marker for B lymphocytes) antibody (47%), and 25 (78%) were positive for monoclonal anti-macrophage and anti-HLA-DR antibodies. IL-1 alpha and IL-2 were detected in the epiretinal membranes in 8 out of 13 tested cases (62%). However, in the vitreous, IL-1 alpha was detected in only 3 out of 13 cases (70, 75 and 80 pg/ml, respectively), while IL-2 was not detected in any of the vitreous samples. The results clearly demonstrate that immune cells and their cytokines were found in about half of the epiretinal membrane specimens. The invasion of the immunocompetent cells in the membranes seems to be a secondary event. They would not participate in the pathogenesis of PDR, but probably induce unspecific reactions and thus complicate the disease.

Cytokines in the Vitreous of Patients With Proliferative Diabetic Retinopathy

Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy.

Basic Fibroblast Growth Factor Levels in the Vitreous of Patients With Proliferative Diabetic Retinopathy

A two-site enzyme-linked immunosorbent assay was used to quantitate levels of basic fibroblast growth factor in the vitreous from 36 patients undergoing vitrectomy for a variety of retinal conditions, including proliferative diabetic retinopathy, macular pucker, and retinal detachment with and without proliferative vitreoretinopathy. Basic fibroblast growth factor levels ranged from undetectable to 52 ng/mL. In patients with proliferative diabetic retinopathy, basic fibroblast growth factor levels were greater than or equal to 30 ng/mL in 8 of 17 specimens. Of the 8 patients with elevated basic fibroblast growth factor levels, 6 had evidence of active proliferative disease (ie, neovascularization of the disc or iris), whereas in the patients who had undetectable levels only 2 of 9 had evidence of neovascularization of disc and none had neovascularization of the iris. In the rhegmatogenous retinal detachment group, 2 of 10 eyes had elevated basic fibroblast growth factor levels, while none in the macular pucker group had elevated levels. Our study documents increased levels of basic fibroblast growth factor in vitreous specimens from patients with proliferative diabetic retinopathy, particularly those with active proliferative retinopathy. The role of basic fibroblast growth factor in the pathogenesis of various retinal disease entities is discussed.

Transmission Electron Microscopic Observations of Vitreous Abnormalities in Retinitis Pigmentosa

Ultrastructural studies of six vitreous biopsy specimens obtained during cataract surgery on patients with retinitis pigmentosa showed four types of cells. These were ocular pigment epithelium, uveal melanocytes, retinal astrocytes, and macrophage-like cells. The fibrous astrocytes displayed plump cell bodies, large nuclei, and numerous intracytoplasmic filaments. The pigment epithelial cells and uveal melanocytes were round to cuboidal and were heavily pigmented. Macrophage-like cells demonstrated round cell bodies, inclusions of glycogen, and long processes extending from the cell membrane. Also identified in the vitreous material were loose pigment granules. In contrast, vitreous from the control group showed occasional macrophages and loose pigment. These findings explained the clinical observation of material within the vitreous of patients with retinitis pigmentosa.

Ophthalmoscopic Observation of Microfilarias in the Vitreous of Patients Infected with Onchocerciasis

Ophthalmoscopic Observation of Microfilarias in the Vitreous of Patients Infected with Onchocerciasis