Interleukin-10 Promotes Pathological Angiogenesis by Regulating Macrophage Response to Hypoxia during Development

Aberrant angiogenesis in the eye is the most common cause of blindness. The current study examined the role of interleukin-10 (IL-10) in ischemia-induced pathological angiogenesis called neovascularization during postnatal development. IL-10 deficiency resulted in significantly reduced pathological retinal angiogenesis. In contrast to the choroicapillaris where IL-10 interferes with macrophage influx, IL-10 did not prevent anti-angiogenic macrophages from migrating to the retina in response to hypoxia. Instead, IL-10 promoted retinal angiogenesis by altering macrophage angiogenic function, as macrophages from wild-type mice demonstrated increased vascular endothelial growth factor (VEGF) and nitric oxide (NO) compared to IL-10 deficient macrophages. IL-10 appears to directly affect macrophage responsiveness to hypoxia, as macrophages responded to hypoxia with increased levels of IL-10 and STAT3 phosphorylation as opposed to IL-10 deficient macrophages. Also, IL-10 deficient macrophages inhibited the proliferation of vascular endothelial cells in response to hypoxia while wild-type macrophages failed to do so. These findings suggest that hypoxia guides macrophage behavior to a pro-angiogenic phenotype via IL-10 activated pathways

Interleukin and Growth Factor Levels in Subretinal Fluid in Rhegmatogenous Retinal Detachment: A Case-Control Study

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. METHODOLOGY: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. FINDINGS: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control

Value of duplex and color doppler ultrasonography in the evaluation of orbital vascular flow and resistance in sickle cell disease

PubMedID: 11391712The aim of the present study was to assess and to compare the orbital and retinal vascular flow dynamics and resistance in patients with homozygous sickle cell disease with controls by means of duplex and color Doppler ultrasonography. Forty-six patients with homozygous sickle cell disease (SCD) and 20 healthy subjects were included in the study. None of the patients had objective signs of ocular involvement. Duplex and color Doppler ultrasonography of the ophthalmic, short posterior ciliary, and central retinal arterial flows of the both eyes were performed to assess peak systolic flow velocity (PSFV), end-diastolic flow velocity (EDFV), and mean flow velocity (MFV) through entire cardiac cycle with further calculation of resistive indices (RI) and pulsatility indices (PI). Ophthalmic arterial flow velocities were significantly increased in patients with SCD than in controls (P < 0.0001). Blood flow velocities of the central retinal artery were found to be significantly reduced (P < 0.0001) while RI and PI values were markedly higher (P < 0.02 and P < 0.03) in patients with SCD compared to controls. Reduction of retinal vascular flow velocities and increase of retinal vascular resistance were significantly related to the mean hemoglobin and hematocrit levels, red blood cell count, and mean corpuscular hemoglobin volume (P < 0.009, P < 0.01, P < 0.02, and P < 0.04, respectively). In conclusion, Doppler ultrasonography in patients with SCD who had no objective signs of ocular involvement allowed detection enhancement of ophthalmic flow velocities, reduced retinal flow velocities, and increased retinal vascular resistance, which are associated with haematological features. © 2001 Wiley-Liss, Inc

Interleukin (IL)-6, interleukin (IL)-8 levels and cellular composition of the vitreous humor in proliferative diabetic retinopathy, proliferative vitreoretinopathy, and traumatic proliferative vitreoretinopathy

PubMedID: 16422002Purpose: To investigate the interleukin (IL)-6 levels, IL-8 levels, and cellular composition of the vitreous humor in patients with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and traumatic PVR. Methods: Vitreous samples from 14 patients with PDR, 10 patients with PVR, and 10 patients with traumatic PVR were analyzed. Fifteen cadaver eyes were used as controls. Cytokine levels were measured by ELISA. Results: Elevated IL-6 levels were detected in the vitreous of 12 (85.7%) of the PDR patients, eight (80%) of the PVR patients, and all (100%) of the traumatic PVR patients. None of the control IL-6 results were elevated. Vitreous IL-8 levels were elevated in 12 (85.7%) of the PDR patients, six (60%) of the PVR patients, all (100%) of the traumatic PVR patients, and one (6.7%) of the control eyes. Cytological examination of the vitreous specimens revealed a predominance of macrophages (50%) in the PDR samples and a predominance of retinal pigment epithelial (RPE) cells (60%) in the PVR samples. In contrast, neutrophils predominated (88%) in the traumatic PVR samples. Conclusion: The findings suggest that IL-6 and IL-8 may be involved in the pathogenesis of PDR, PVR, and traumatic PVR. High proportions of RPE cells and macrophages are associated with elevated IL-6 and IL-8 levels in the vitreous of PDR and PVR patients; however, the fact that these cells are not predominant in traumatic PVR suggests that different immune response mechanisms may be active in the pathogenesis of these disorders. Copyright © Taylor & Francis Inc

Human T-lymphotrophic virus type-I antibodies in uveitis and leukemia patients in southern Turkey

Purpose: Human T-lymphotrophic virus type-I is a human retrovirus, that has been reported all around the world in recent years. It has been shown to be associated with different disease entities, such as adult T-cell leukemia/lymphoma, spastic paraparesis and uveitis. Until now, HTLV-I seropositivity has not been shown in the Turkish population. Methods: In the present study, HTLV-I antibodies were explored in the sera of 41 patients with idiopathic uveitis, 10 with Behcet's disease and 38 with leukemia, and in 96 controls, in order to evaluate the seropositivity of the virus in southern Turkey, and to estimate its role in uveitis and leukemia. Results: Although no HTLV-I antibodies were detected in our controls, the global, occurrence of HTLV-I seropositivity states the importance of screening in blood donors. None of the patients with uveitis were found to have HTLV-I antibodies, however we believe in that HTLV-I should be taken into consideration in evaluating the aetiopatogenesis of uveitis in our region, as large series of HTLV-I uveitis were reported from different regions of the world. The positivity of HTLV-I antibodies in 12 leukemia patients in our series needs further investigation. Conclusion: conclusion, studies performed on larger series are needed in order to evaluate the seropositivity of HTLV-I in Turkey, and its role in the occurrence of ueitis

Vasculitis induced by zafirlukast therapy

PubMedID: 12189465Zafirlukast is a leukotriene inhibitor that has recently been approved for the prophylaxis of asthma. Although this new product has been well accepted because of its convenient dosing and relatively few side effects, several cases of Churg-Strauss syndrome have been reported to be associated with its use. In this paper we describe the case of a 54-year-old white man with no history of corticosteroid therapy in whom leukocytoclastic vasculitis, hepatitis and eosinophilia developed while he was on zafirlukast therapy for mild asthma