Publications (2)9.38 Total impact
-
Article: Multiplex bead analysis of vitreous humor of patients with vitreoretinal disorders.
[show abstract] [hide abstract]
ABSTRACT: Vitreoretinal disorders are frequently characterized by increased vitreous levels of cellular mediators, including cytokines, chemokines, and growth factors. The study was conducted to investigate whether multiplex bead analysis could identify disease-specific profiles of these mediators in a variety of vitreoretinal diseases. Levels of 19 mediators were measured: the cytokines IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF, IFN-gamma, granulocyte-macrophage-colony-stimulating factor (GM-CSF), and granulocyte-stimulating factor (G-CSF); the chemokines CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL8; and the growth factors epidermal growth factor (EGF), FGF, and VEGF, by using multiplex bead analysis of vitreous humor of 58 eyes undergoing vitrectomy for a variety of vitreoretinal disorders. The predominant mediators detected were IL-6, CXCL8, and CCL2. The most complex pattern of mediators was seen in patients with proliferative vitreoretinopathy (PVR) and included a mixture of cytokines, chemokines, and growth factors. Patients with chronic uveitis showed a limited mediator pattern that did not suggest either a Th1 or Th2 response. By comparison, patients with lens-induced uveitis (LIU) showed significantly greater levels of cytokines than did patients with chronic uveitis, including IFN-gamma and IL-12, with a trend toward an acute Th1 inflammatory response. Moreover, in samples from patients with LIU, CXCL8 inversely correlated with time after initial surgery and duration of treatment. Multiplex bead analysis allows the measurement of multiple mediators from a single vitreous sample. The data confirm patterns of mediators previously described in different vitreoretinal conditions. In addition, LIU mediator levels correlate with duration of treatment and time after cataract surgery.Investigative Ophthalmology & Visual Science 06/2007; 48(5):2203-7. · 3.60 Impact Factor -
Article: Topical glucocorticoid therapy directly induces up-regulation of functional CXCR4 on primed T lymphocytes in the aqueous humor of patients with uveitis.
[show abstract] [hide abstract]
ABSTRACT: Overexpression of the constitutive chemokine receptor CXCR4 has been shown to contribute to the accumulation of leukocytes at sites of chronic inflammation. Glucocorticoids are widely used to treat inflammatory disorders such as uveitis to considerable effect, yet paradoxically have been reported to increase CXCR4 expression in vitro. We show here that ocular lymphocytes isolated from patients with uveitis who had been treated with topical glucocorticoids expressed highly elevated levels of CXCR4. The up-regulation of CXCR4 could be reproduced in vitro by culture of CD4(+) T cells with aqueous humor (AqH), indicating a role for the ocular microenvironment rather than preferential recruitment of CXCR4(+) cells. Untreated uveitis and noninflammatory AqH up-regulated CXCR4 to a limited extent; this was dependent on TGF-beta2. However, the highest levels of CXCR4 both in vivo and in vitro were found in the glucocorticoid-treated patients. Glucocorticoids appeared to be directly responsible for the induction of CXCR4 in treated patients, as the glucocorticoid receptor antagonist RU38486 inhibited the in vitro up-regulation by AqH from these patients. Dexamethasone selectively up-regulated CXCR4 in vitro, but not any of a wide range of other chemokine receptors. CXCL12, the ligand for CXCR4, was present in AqH under noninflammatory conditions, but the levels were low in untreated uveitis and undetectable in treated uveitis AqH. The importance of these results for the treatment of HIV patients with glucocorticoids is discussed as well as a role for glucocorticoid-induced CXCR4 up-regulation and CXCL12 down-regulation in controlling the migration of lymphocyte populations, resulting in resolution of inflammation.The Journal of Immunology 07/2004; 172(11):7154-61. · 5.79 Impact Factor
