Brief research report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells.

Intercellular adhesion molecule 1 (ICAM-1) is a central cell adhesion molecule for retinal transendothelial migration of the leukocytes in non-infectious posterior uveitis. Inhibiting gene transcription reduces induction of ICAM-1 in inflamed retinal endothelium. Based on published literature implicating transcription factor ETS-1 as an activator of gene transcription, we investigated the effect of ETS-1 blockade on ICAM-1 levels in cytokine-stimulated human retinal endothelial cells.

Metabolic reprogramming of the retinal pigment epithelium by cytokines associated with age-related macular degeneration.

The complex metabolic relationship between the retinal pigment epithelium (RPE) and photoreceptors is essential for maintaining retinal health. Recent evidence indicates the RPE acts as an adjacent lactate sink, suppressing glycolysis in the epithelium in order to maximize glycolysis in the photoreceptors. Dysregulated metabolism within the RPE has been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss.

Effects of tumor necrosis factor-α and interleukin-1β on human retinal endothelial cells.

Uveitis, or intraocular inflammation, is a potentially blinding condition that mostly affects the working-age population. The cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play a role in the pathogenesis of non-infectious uveitis and have been linked to the breakdown of the inner blood-retinal barrier, composed mainly of retinal endothelial cells, leading to macular oedema and vascular leakage. However, the effects of TNF-α and IL-1β on human retinal endothelial function are not fully understood.

Dengue Virus Infection of Human Retinal Müller Glial Cells.

Retinopathy is a recently recognized complication of dengue, affecting up to 10% of hospitalized patients. Research on the pathogenesis has focused largely on effects of dengue virus (DENV) at the blood-retinal barrier. Involvement of retinal Müller glial cells has received little attention, although this cell population contributes to the pathology of other intraocular infections.

Human retinal endothelial cells express functional interleukin-6 receptor.

Background: Interleukin (IL)-6 is an inflammatory cytokine present in the eye during non-infectious uveitis, where it contributes to the progression of inflammation. There are two major IL-6 signaling pathways: classic signaling and trans-signaling. Classic signaling requires cellular expression of the IL-6 receptor (IL-6R), which exists in membrane-bound (mIL-6R) and soluble (sIL-6R) forms.

Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding.

The interaction between leukocytes and cytokine-activated retinal endothelium is an initiating step in non-infectious uveitis involving the posterior eye, mediated by cell adhesion molecules. However, because cell adhesion molecules are required for immune surveillance, therapeutic interventions would ideally be employed indirectly. Using 28 primary human retinal endothelial cell isolates, this study sought to identify transcription factor targets for reducing levels of the key retinal endothelial cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, and limiting leukocyte binding to the retinal endothelium.

Expression of Long Non-Coding RNAs in Activated Human Retinal Vascular Endothelial Cells.

Purpose: Retinal endothelial cell activation is a central event in non-infectious posterior uveitis. There is recent interest in long non-coding (lnc)RNA-targeted therapeutics for retinal diseases. We aimed to identify human retinal endothelial cell lncRNAs that might be involved in activation.

Transcriptomic Responses of Human Retinal Vascular Endothelial Cells to Inflammatory Cytokines.

Purpose: Molecular profiling of human retinal endothelial cells provides opportunities to understand the roles of this cell population in maintenance of the blood-ocular barrier, and its involvements in diverse retinal vasculopathies. We aimed to generate a transcriptome of human retinal endothelial cells in the unstimulated state, and following treatment with inflammatory cytokines linked to cell dysfunction.

Methods: Endothelial cells were isolated from retinae of five human cadaveric donors, and treated for 60 minutes and 24 hours with interleukin-1β or tumor necrosis factor-α, or exposed to medium alone for the same intervals.

Infection of Human Retinal Pigment Epithelial Cells with Dengue Virus Strains Isolated during Outbreaks in Singapore.

Prevalence of dengue retinopathy varies across epidemics, with the disease linked to circulation of dengue virus serotype 1 (DENV-1). The retinal pigment epithelium has been implicated in the pathology. We investigated infectivity, molecular response, and barrier function of epithelial cells inoculated with DENV strains from different outbreaks in Singapore.

Zika Virus Infection of Human Iris Pigment Epithelial Cells.

During recent Zika epidemics, adults infected with Zika virus (ZIKV) have developed organ-specific inflammatory complications. The most serious Zika-associated inflammatory eye disease is uveitis, which is commonly anterior in type, affecting both eyes and responding to corticosteroid eye drops. Mechanisms of Zika-associated anterior uveitis are unknown, but ZIKV has been identified in the aqueous humor of affected individuals.

Model Systems for Studying Mechanisms of Ocular Toxoplasmosis.

The most common human disease caused by infection with Toxoplasma gondii is ocular toxoplasmosis, which typically is manifest as recurrent attacks of necrotizing retinal inflammation with subsequent scarring. The multilayered retina contains specialized cell populations, including endothelial cells, epithelial cells, neurons and supporting cells, all of which may be involved in this condition. In vitro investigations of basic mechanisms operating in human ocular toxoplasmosis use cellular and molecular methods that are common to the study of many pathological processes, and the novel aspect of this research is the use of human retinal cell subsets.

Neutrophil Activities in Human Ocular Toxoplasmosis: An In Vitro Study With Human Cells.

Purpose: Retinal damage in ocular toxoplasmosis reflects Toxoplasma gondii-induced cell lysis and reactive inflammation. Human retinal histopathology demonstrates the presence of neutrophils, but activities of this leukocyte subset are unstudied. We conducted in vitro experiments to evaluate roles for neutrophils as retinal taxis for T.

Expression of Long Non-Coding RNAs by Human Retinal Müller Glial Cells Infected with Clonal and Exotic Virulent .

Retinal infection with -ocular toxoplasmosis-is a common cause of vision impairment worldwide. Pathology combines parasite-induced retinal cell death and reactive intraocular inflammation. Müller glial cells, which represent the supporting cell population of the retina, are relatively susceptible to infection with .

Immunological Molecular Responses of Human Retinal Pigment Epithelial Cells to Infection With .

Ocular toxoplasmosis is the commonest clinical manifestation of infection with obligate intracellular parasite, . Active ocular toxoplasmosis is characterized by replication of tachyzoites in the retina, with reactive inflammation. The multifunctional retinal pigment epithelium is a key target cell population for .

Erratum to "Molecular Responses of Human Retinal Cells to Infection with Dengue Virus".

[This corrects the article DOI: 10.1155/2017/3164375.].

Selection of Reference Genes for Studies of Human Retinal Endothelial Cell Gene Expression by Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction.

Background: Human retinal endothelial cells are employed increasingly for investigations of retinal vascular diseases. Analysis of gene expression response to disease-associated stimuli by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) is common. However, most reported work does not follow the minimum information for publication of qPCR experiments (MIQE) recommendation that multiple, stably expressed reference genes be used for normalization.

ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells.

Objective: Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized.

Effect of NADPH oxidase 1 and 4 blockade in activated human retinal endothelial cells.

Background: Over-production of reactive oxygen species (ROS) and resulting oxidative stress contribute to retinal damage in vascular diseases that include diabetic retinopathy, retinopathy of prematurity and major retinal vessel occlusions. NADPH oxidase (Nox) proteins are professional ROS-generating enzymes, and therapeutic targeting in these diseases has strong appeal. Pharmacological inhibition of Nox4 reduces the severity of experimental retinal vasculopathy.

Retinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye.

Purpose: Success of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells.

The role of PKCζ in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil.

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression.

Molecular Responses of Human Retinal Cells to Infection with Dengue Virus.

Recent clinical reports indicate that infection with dengue virus (DENV) commonly has ocular manifestations. The most serious threat to vision is dengue retinopathy, including retinal vasculopathy and macular edema. Mechanisms of retinopathy are unstudied, but observations in patients implicate retinal pigment epithelial cells and retinal endothelial cells.

Molecular Signals Involved in Human B Cell Migration into the Retina: In Vitro Investigation of ICAM-1, VCAM-1, and CXCL13.

Purpose: B cells participate in diverse retinal immunopathologies. Endothelial adhesion molecules and chemokines direct leukocyte trafficking. We examined the involvement of three molecular signals in retinal transendothelial migration of human B cells: ICAM-1, VCAM-1, and CXCL13.

Targeting Endothelial Adhesion Molecule Transcription for Treatment of Inflammatory Disease: A Proof-of-Concept Study.

Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system.

Protein kinase cα regulates the expression of complement receptor Ig in human monocyte-derived macrophages.

The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages.