Identification of α-fodrin as an autoantigen in experimental coronavirus retinopathy (ECOR).

The coronavirus, mouse hepatitis virus (MHV), JHM strain induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop either the late phase or autoimmune reactivity. A mouse RPE/choroid DNA expression library was screened using sera from virus infected BALB/c mice.

Who pays the toll for solving the enigma of corneal herpes?

In herpetic stromal keratitis (HSK), herpes simplex virus type-1 DNA fragments and herpes simplex virus-immunoglobulin G immune complexes are present in corneas long after the infective virus has disappeared. These viral components are highly immunogenic and potentiate the production of proinflammatory cytokines and chemokines via Toll-like receptors expressed on corneal cells and macrophages. In addition, angiogenic factors, such as the vascular endothelium growth factor and the tissue-damaging enzyme, matrix metalloproteinase 9, are induced by corneal cells and macrophages through the recognition of these viral components in the pathogenesis of HSK.

Inhibition of HSV-1 by chemoattracted neutrophils: supernatants of corneal epithelial cells (HCE) and macrophages (THP-1) treated with virus components chemoattract neutrophils (PMN), and supernatants of PMN treated with these conditioned media inhibit viral growth.

The role of PMNs (neutrophils) in corneal herpes was studied using an in vitro system. Human corneal cells (HCE) and macrophages (THP-1) infected with HSV-1 or treated with virus components (DNA or virus immune complexes) released chemokines, which attracted PMNs. Highly reactive oxygen species were detected in PMNs.

Role of human herpes virus 6 in corneal inflammation alone or with human herpesviruses.

Purpose: : The purpose of this study was to determine the association of human herpes virus 6 (HHV-6) and/or other human herpesviruses in corneal inflammation using polymerase chain reaction (PCR).

Methods: : We collected tear films, conjunctival smears, and a corneal button of inflamed cornea, and the presence of HHV-6 and other herpesviruses in these samples were assessed by a nested PCR.

Results: : In tear films collected from 3 of 9 patients with dendritic keratitis, HHV-6 DNA was positive twice, together with herpes simplex virus (HSV) or varicella zoster virus DNA most often, during the acute phase of the disease.

HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9.

Angiogenesis and inflammatory mediators are critical pathogenic factors in herpetic stromal keratitis (HSK). Since disease progresses without infectious virus, HSV-DNA and HSV-IgG complexes (HSV-IC) may contribute to HSK by triggering these factors. Production of VEGF and MMP-9 was studied in vitro using corneal epithelial cells (HCE), fibroblasts (HCRF) and macrophages (THP-1).

Who (what) pays toll for the development of herpetic stromal keratitis (HSK).

In the herpetic stromal keratitis (HSK), HSV DNA fragments and HSV-IgG immune complexes (HSV-IC) are present in most of the corneas long after infective virus has disappeared. These viral components are highly immunogenic and potentiate production of proinflammatory cytokines and chemokines via Toll-like receptors (TLRs) expressed on the corneal cells and macrophages. In addition angiogenic factors, such as vascular endothelium growth factor (VEGF) and the tissue damaging enzyme matrix metalloproteinase 9 (MMP-9) deeply involved in the pathogenesis of HSK, are also induced by corneal cells and macrophages through the recognition of these viral components.

IFN-beta provides immuno-protection in the retina by inhibiting ICAM-1 and CXCL9 in retinal pigment epithelial cells.

The retinal pigment epithelial (RPE) cell is a potent regulatory cell that facilitates normal physiologic processes and plays a critical role in a variety of retinal diseases. We evaluated IFN-beta production in human RPE cells through TLR signaling and investigated the effects of IFN-beta on RPE cells. RPE cells treated with poly(I:C) or infected with an RNA virus produce IFN-beta.

Experimental coronavirus retinopathy (ECOR): retinal degeneration susceptible mice have an augmented interferon and chemokine (CXCL9, CXCL10) response early after virus infection.

Mouse hepatitis virus induces a biphasic disease in BALB/c mice that consists of an acute retinitis followed by progression to a chronic retinal degeneration with autoimmune reactivity. Retinal degeneration resistant CD-1 mice do not develop the late phase. What host factors contribute to the distinct responses to the virus are unknown.

Corneal buttons obtained from patients with HSK harbor high copy numbers of the HSV genome.

Purpose: To detect herpes simplex virus (HSV) genome in the cornea, we sampled the limbal corneas and scleras of the imported eye bank eyes and recipient's corneal buttons and quantitated HSV genome in them by real-time polymerase chain reaction (PCR).

Methods: Forty-four recipient corneas including 7 corneas with and 37 corneas without a history of herpetic keratitis, 70 eye bank donor limbal corneas, and 35 eye bank donor scleras were obtained. Primers for real-time PCR were synthesized using the HSV-1 and -2 common regions of the viral DNA polymerase.

Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1-human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors.

Toll-like receptor 3 (TLR-3) and TLR-9 gene expression and interleukin 6 (IL-6) secretion were studied in corneal cells with components of herpes simplex virus (HSV). Human corneal epithelial cells (HCEs) and primary human corneal fibroblasts (HCRFs) were infected with live HSV or UV-inactivated HSV (UV-HSV), transfected with HSV DNA or treated with HSV-anti-HSV IgG immune complexes. Gene expression of TLR-3 and -9 was analysed by real-time PCR.

Human cytomegalovirus induced cyclooxygenase-2 in human retinal pigment epithelial cells augments viral replication through a prostaglandin pathway.

Cytomegalovirus (CMV) retinitis is characterized by alterations in retinal cell function and host responses to virus replication. The goal of this study was to evaluate the induction of cyclooxygenase-2 (COX-2) and prostaglandin (PGE) in CMV infected human retinal pigment epithelial (RPE) cells and to determine their effect on virus replication. CMV immediate early (IE) protein and COX-2 proteins were identified in RPE cells in retinal tissue sections from patients with CMV retinitis.

Retinal degeneration in experimental coronavirus retinopathy (ECOR) is associated with increased TNF-alpha, soluble TNFR2 and altered TNF-alpha signaling.

Experimental coronavirus retinopathy (ECOR) is a virally triggered model of retinal degeneration composed of both genetic and autoimmune components. Since TNF-alpha plays a role in immune-mediated processes we evaluated the levels of TNF-alpha/TNF-alpha receptors and the downstream signaling molecule nitric oxide (NO) during disease in both retinal degeneration susceptible BALB/c and degeneration resistant CD-1 mice. Following coronavirus injection, TNF-alpha mRNA was detected at higher levels within the retinas, and concentrations of TNF-alpha (p<0.