Retinoblastoma (Rb) is the most common primary intraocular tumor in children. Local treatment of disease usually effective if diagnosed early; however advanced Rb can metastasize through routes that involve invasion choroid, sclera and optic nerve or more broadly via ocular vasculature. Metastatic patients have very high mortality rates. While current therapy for directed toward blocking cell division growth, there are no specific treatments targeted to block metastasis. Two such targets...

Pathological mechanisms underlying diabetic retinopathy are still not completely understood. Increased understanding of potential cellular pathways responsive to hyperglycemia is essential develop novel therapeutic strategies for retinopathy. A growing body evidence shows that microRNA (miRNA) play important roles in pathological involved retinopathy, as well possessing targets. The hypothesis this study was miR-146a plays a key role attenuating hyperglycemia-induced inflammatory through...

The goals of this study were 2-fold: 1) to determine whether stimulation Eph B4 receptors promotes microvascular endothelial cell migration and/or proliferation, and 2) elucidate signaling pathways involved in these responses. human cells used possessed abundant with no endogenous ephrin B2 expression. Stimulation B2/Fc chimera resulted dose- time-dependent phosphorylation Akt. These responses inhibited by LY294002 ML-9, blockers phosphatidylinositol 3-kinase (PI3K) Akt, respectively....

Regional influences of parasympathetic and sympathetic innervation on choroidal blood flow were investigated in anesthetized rats. Parasympathetic pterygopalatine neurons activated by electrically stimulating the superior salivatory nucleus, whereas cervical trunk stimulation uveal was measured laser Doppler flowmetry. increased flux anterior choroid nasal vortex veins but not posterior choroid. Vasodilation blocked completely neuronal nitric oxide synthase inhibitor...

Purpose. Super-selective intra-ophthalmic artery chemotherapy (SSIOAC) is an eye-targeted drug-delivery strategy to treat retinoblastoma, the most prevalent primary ocular malignancy in children. Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, commonly used chemotherapeutic. Methods. To explore reasons for unexpected toxicities, we examined effects of as well carboplatin (another chemotherapeutic retinoblastoma), vitro human retinal...

Mechanisms underlying the pathology of diabetic retinopathy are still not completely understood. Increased understanding potential cellular pathways responsive to hyperglycemia is essential develop novel therapeutic strategies for retinopathy. Emerging evidence shows impact microRNA (miR) as a target. The purpose our study was test hypothesis that miR-15b and miR-16 altered by in retinal endothelial cells (REC), miR-15b/16 play key roles regulating insulin signaling through reduction TNFα-...

Hyperglycemia is a significant risk factor for diabetic retinopathy and induces increased inflammatory responses retinal leukostasis, as well vascular damage. Although there an increasing amount of evidence that miRNA may be involved in the regulation pathology retinopathy, mechanisms by which mediate cellular to control onset progression are still unclear. The purpose our study was investigate hypothesis miR-15a/16 inhibit pro-inflammatory signaling reduce leukostasis. We generated...

To determine whether Compound 49b, a novel PKA-activating drug, can prevent diabetic-like changes in the rat retina through increased insulin-like growth factor binding protein-3 (IGFBP-3) levels.For cell culture studies, we used both human retinal endothelial cells (REC) and Müller either 5 mM (normal) or 25 (high) glucose. Cells were treated with 50 nM 49b alone of following treatment protein kinase A (PKA) siRNA IGFBP-3 siRNA. Western blotting ELISA analyses done to verify PKA knockdown,...

Sympathetic nerves may play a role in vascular disorders of the eye. In present study, we hypothesized that activation β3-adrenergic receptors on retinal endothelial cells would promote migration and proliferation these cells, two markers an angiogenic phenotype. We show, for first time, expression cultured cells. Activation with BRL37344, specific receptor agonist, promoted was blocked by inhibitors phosphatidylinositol 3-kinase (PI3K), mitogen activated protein kinase component MEK, matrix...

To determine whether beta-adrenergic receptors are involved in the modulation of inflammatory cytokines Müller cells a hyperglycemic environment.Rat were grown high (25 mM)- or low (5 mM)-glucose medium. lysates processed for real-time polymerase chain reaction to measure steady state mRNA expression following markers: iNOS, TNF-alpha, IL-1B, and ICAM-1. Western blot analysis ELISA assays performed protein levels these markers PGE2 content.Isoproterenol treatment significantly decreased...

Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β -adrenergic receptor agonist, Compound 49b, reduced Toll-like 4 (TLR4) signaling in endothelial cells (REC) grown high glucose. Others TLR4 activates high-mobility group box 1 (HMGB1), which has been associated with the NOD-like 3 (NLRP3) inflammasome. Thus, we hypothesized Epac1, downstream mediator receptors, would block TLR4/HMGB1-mediated stimulation NLRP3 inflammasome, leading to...

During pregnancy in several species including humans and rodents, the endometrium undergoes decidualization. This process of differentiation from endometrial to decidual tissue occurs only after onset implantation mice. It can also be artificially induced causing formation deciduomal tissue. The purpose this study was compare gene expression profile developing decidua pregnant mice with deciduoma formed artificial induction an effort identify conceptus-influenced changes uterine during We...

We describe the histopathologic findings in a nonhuman primate (NHP) model of superselective intraophthalmic artery chemotherapy (SSIOAC), detailing ocular and orbital vascular adverse effects.To further document, using comprehensive histopathology, previously reported toxic effects observed with real-time ophthalmoscopy during SSIOAC NHP model.Comparative interventional case series.Preclinical trial approved under guidelines Institutional Animal Care Utilization committee.Six adult male...

We hypothesized that loss of insulin-like growth factor binding protein 3 (IGFBP-3) signaling would produce neuronal changes in the retina similar to early diabetes.To understand better role IGFBP-3 retina, knockout (KO) mice were evaluated for neuronal, vascular, and functional compared wild-type littermates. also cultured retinal endothelial cells (REC) normoglycemia or hyperglycemia determine interaction between TNF-α, as data indicate both proteins are regulated by β-adrenergic receptors...

Loss of functional retinal ganglion cells (RGC) is an element degeneration that poorly understood. This in part due to the lack a reliable and validated protocol for isolation primary RGCs. Here, we optimize feasible, reproducible, standardized flow cytometry-based enrichment homogeneous RGC with Thy1.2hiCD48negCD15negCD57neg surface phenotype. A three-step validation process was performed by (1) genomic profiling 25-genes associated cells, (2) intracellular labeling sorted RGC-markers SNCG,...

Damage associated molecular pattern (DAMPs), such as high mobility group box 1 (HMGB1), may be involved in retinal inflammation response to glucose. To test whether HMGB1 inhibition could protect the diabetic retina, C57BL/6J mice were made and treated with glycyrrhizin, a inhibitor, for up six months. Measurements of permeability, neuronal, vascular changes done, well assessments HMGB1, tumor necrosis factor alpha (TNFα), interleukin-1-beta (IL1β) levels. Retinal endothelial cells (REC)...

The role of high mobility group box 1 (HMGB1) in acute diabetic retinal damage has been demonstrated. We recently reported that glycyrrhizin, a HMGB1 inhibitor, protected the retina against neuronal, vascular, and permeability changes. In this study, we wanted to investigate exchange protein for cAMP (Epac1) on actions glycyrrhizin. Using endothelial cell specific knockout mice Epac1, made some using streptozotocin, treated with glycyrrhizin up 6 months. measured permeability, vascular...

To determine whether loss of sympathetic innervation alters basement membrane thickness and pericyte loss.Sympathetic to the eye was destroyed by surgical removal right superior cervical ganglion in rats. Basement changes were assessed real-time PCR electron microscopy. The number pericytes measured immunofluorescent staining for NG2 proteoglycan. Steady-state mRNA levels also evaluated platelet-derived growth factor-BB (PDGF-BB).Loss caused a significant increase steady state fibronectin...