Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this report, we demonstrate that herpes simplex virus (HSV) infection of the cornea results in the upregulation of the matrix-degrading metalloproteinase enzyme MMP-9. This enzyme was shown to contribute to the neovascularization process that occurs in the corneal stroma in response to HSV infection. The likely source of MMP-9, at least initially after infection, was neutrophils that were signaled to invade the cornea soon after infection. Corneal infiltrating neutrophils were shown to express MMP-9, and preventing the neutrophil response with specific mAb diminished MMP-9 expression as well as the extent of angiogenesis. Further supporting a role for MMP-9 in HSV-induced corneal angiogenesis was the observation that inhibition of MMP-9 with the specific inhibitor TIMP-1 resulted in reduced angiogenesis. In addition, angiogenesis was diminished in ocularly infected MMP-9 knockout mice. Our results demonstrate that MMP-9 is involved in angiogenesis caused by HSV. Since angiogenesis appears to represent a vital step in the pathogenesis of herpetic stromal keratitis, these results indicate that targeting MMP-9 for inhibition should prove useful for the therapy of herpetic stromal keratitis.
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PMID:Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus. 1239 46

A total of 439 patients (adults--184, children--255) with herpetic keratitis as well as with uveitis and choriorenitis of different geneses and localizations were examined. An aggravation of HSV-infection was determined by detecting, in the blood), anti-bodies to the unstructured early viral antigens by using the immune enzyme analysis (IEA). The efficiency of the test was demonstrated during the examination of patients with different ophthalmic pathologies. An active infection was detected in 16-39% of patients with various ocular diseases of non-herpetic etiology. The pathogenetic value of reactivated HSV infection is diverse: it can function as an etiological or trigger factor and it can aggravate the main disease through causing, postoperatively, complications.
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PMID:[Diagnosis and importance of the opportunistic herpes-virus infection in etiology and pathogenesis of different eye diseases]. 1280 Apr 84

Herpes simplex virus (HSV) infection of the eye can induce epithelial and stromal keratitis and may also lead to postoperative endothelial failure in keratoplasty. Clinical symptoms and/or virus culture of corneal scrapings most frequently provide the basis for diagnosis of ocular HSV infection, and although HSV DNA has been shown to be present in the cornea, its role in success or failure of corneal grafts remains unclear. In this study, a PCR assay was used to detect HSV DNA in corneal buttons of 38 corneal graft recipients and in donor scleral remnants, retaining one-half of each sample for subsequent viral isolation. Recipients were followed up clinically for a period of 6 months after keratoplasty. All recipients but three were found to be HSV seropositive. Eight recipient corneal buttons contained detectable HSV DNA (7 HSV-1, 1 HSV-2, the latter case confirmed by viral culture). Two donor corneas were found positive for HSV-1 DNA, with negative cultures, and endothelial graft failure occurred in one of the matching recipients after 4 months. One recipient with no history of herpes contracted herpetic keratitis 4 months after keratoplasty, even though the corneal button and donor scleral remnants contained no detectable HSV DNA. The study confirms previous observations of HSV DNA in the corneal tissue of HSV seropositive patients apparently unrelated to any clinical manifestation of herpes infection. However, as demonstrated by culture, HSV remains infectious and may therefore induce donor-to-host infection in corneal recipients.
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PMID:Herpes simplex virus DNA in corneal transplants: prospective study of 38 recipients. 1285 11

Ocular infection with HSV results in a blinding immunoinflammatory lesion known as herpetic stromal keratitis (HSK). Early preclinical events include inflammatory cell, mainly neutrophils, infiltration of the stroma, and neovascularization. To further evaluate the role of neutrophils in pathogenesis, HSV infection was compared in BALB/c and mice of the same background, but lacking CXCR2, the receptor for chemokines involved in neutrophil recruitment. Our results show clear differences in the outcome of ocular HSV infection in CXCR2-/- compared with control BALB/c mice. Thus, CXCR2-/- animals had minimal PMN influx during the first 7 days postinfection, and this correlated with a longer duration of virus infection in the eye compared with BALB/c mice. The CXCR2-/- mice were also more susceptible to HSV-induced lesions and developed HSK upon exposure to a dose of HSV that was minimally pathogenic to BALB/c mice. The basis for the greater HSK lesion susceptibility of CXCR2-/- mice was associated with an elevated IL-6 response, which appeared in turn to induce the angiogenic factor, vascular endothelial growth factor. Our results serve to further demonstrate the critical role of angiogenesis in the pathogenesis of ocular lesions.
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PMID:CXCR2-/- mice show enhanced susceptibility to herpetic stromal keratitis: a role for IL-6-induced neovascularization. 1470 2

Herpes simplex ocular infection is the leading cause of infectious corneal blindness in the United States and presents a frequent challenge to ophthalmologists. The epithelial infections are usually readily controlled with trifluridine or vidarabine, but clinical resistance may be emerging, and host toxicity remains a problem in chronic cases. Acyclovir offers an alternative, and the oral form appears to be an effective antiviral prophylaxis in stromal keratitis and post-penetrating keratoplasty, as well as a treatment for epithelial infections in patients where administration of topical therapy is difficult. Valacyclovir and perhaps famciclovir may provide similar efficacy as acyclovir at reduced doses. In addition, better control of inflammation with potent steroids used at the appropriate phases of HSV infection can minimize scarring and vascularization. Newer agents attempt to provide more specific therapy for both the infectious and inflammatory components of HSV ocular infections.
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PMID:Herpes simplex virus ocular infections. 1509 53

Ocular infection with herpes simplex virus (HSV) results in a blinding immunoinflammatory stromal keratitis (SK) lesion. Early preclinical events include polymorphonuclear neutrophil (PMN) infiltration and neovascularization in the corneal stroma. We demonstrate here that HSV infection of the cornea results in the upregulation of the cyclooxygenase 2 (COX-2) enzyme. Early after infection, COX-2 was produced from uninfected stromal fibroblasts as an indirect effect of virus infection. Subsequently, COX-2 may also be produced from other inflammatory cells that infiltrate the cornea. The induction of COX-2 is a critical event, since inhibition of COX-2 with a selective inhibitor was shown to reduce corneal angiogenesis and SK severity. The administration of a COX-2 inhibitor resulted in compromised PMN infiltration into the cornea, as well as diminished corneal vascular endothelial growth factor levels, likely accounting for the reduced angiogenic response. COX-2 stimulation by HSV infection represents a critical early event accessible for therapy and the control of SK severity.
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PMID:Role of inflammatory cytokine-induced cyclooxygenase 2 in the ocular immunopathologic disease herpetic stromal keratitis. 1605 51

In primary ocular herpes simplex virus (HSV) infection, nitric oxide may function to control viral replication and herpetic stromal keratitis (HSK) lesions. Recurrent HSK, manifested as corneal opacity and neovascularization, is the potentially blinding sequel to primary infection. Here, we assess the effects of nitric oxide synthase inhibition on a mouse model of recurrent HSK. In preliminary primary infection experiments, NIH inbred mice treated with aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), experienced no changes in post-infection tear, brain, or ganglia virus titers, but encephalitis-related mortality was elevated. After UV-B stimulated viral reactivation, iNOS inhibition did not affect virus shedding or clinical disease. In contrast to primary HSK, there was no exacerbation of mortality in recurrent disease. Our findings indicate that nitric oxide can be neuroprotective without antiviral effects in primary HSK, and does not play a significant role in the pathogenesis of recurrent HSK. Compared with data from other mouse strains, this work suggests that there may be a genetic component to the importance of NO in controlling ocular HSV infection.
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PMID:The effects of aminoguanidine on primary and recurrent ocular herpes simplex virus infection. 1612 22

This report evaluates the role of interaction between glucocorticoid-induced tumor necrosis factor receptor (GITR) and GITR ligand (GITR-L) in the immuno-inflammatory response to infection with herpes simplex virus (HSV). Both GITR and GITR-L were transiently upregulated after ocular HSV infection, on antigen-specific T cells and antigen-presenting cells, respectively, in the draining lymph node (DLN). In addition, virus-specific T-cell responses in the DLN and spleen were enhanced by anti-GITR antibody treatment, an outcome expected to result in more severe inflammatory lesions. Intriguingly, the treatment resulted in significantly diminished T-cell-mediated ocular lesions. The explanation for these findings was that anti-GITR antibody treatment caused a reduced production of ocular MMP-9, a molecule involved in ocular angiogenesis, an essential step in the pathogenesis of herpetic keratitis. Our results are the first observations to determine in vivo kinetics of GITR and GITR-L expression after virus infection, and they emphasize the role of GITR-GITR-L interaction to regulate virus-induced immuno-inflammatory lesions.
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PMID:In vivo kinetics of GITR and GITR ligand expression and their functional significance in regulating viral immunopathology. 1614 Jul 69

Herpes stromal keratitis (HSK) results from infection of herpes simplex virus (HSV) in the cornea. Recurrent HSV infection is a leading cause of corneal scarring and visual loss. Although it is generally thought that HSK is the result of an immune response to one or more viral proteins, no viral proteins have been detected in HSK corneas. Thus, the viral proteins involved in HSK, if any, remain undetermined. In contrast, it is reported here that when HSK corneal buttons from latently infected rabbits were fixed using standard procedures, the important immediate-early HSV-1 protein ICP0 was readily detected in the fixative by Western blotting. Similarly, when HSK corneal buttons were soaked in buffer (rather than fixative), ICP0 was readily detected in the soaking buffer. Other HSV-1 proteins were not detected either in the fixative or in the soaking buffer. It is also reported here that ICP0 was consistently detected in virus-free tears from the eyes of rabbits acutely infected with HSV-1. These results suggest that ICP0 rapidly diffuses out of the cornea and may explain why ICP0 was detected in the fixative of HSK corneas and in the soaking buffer of acutely infected corneas.
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PMID:Herpes simplex virus type 1 immediate-early protein ICP0 diffuses out of infected rabbit corneas. 1622 19

Herpes simplex viruses (HSV) are highly pervasive pathogens in the human host with a seroconversion rate upwards of 60% worldwide. HSV type 1 (HSV-1) is associated with the disease herpetic stromal keratitis, the leading cause of infectious corneal blindness in the industrialized world. Individuals suffering from genital herpes associated with HSV type 2 (HSV-2) are found to be two- to threefold more susceptible in acquiring human immunodeficiency virus (HIV). The morbidity associated with these infections is principally due to the inflammatory response, the development of lesions, and scarring. Chemokines have become an important aspect in understanding the host immune response to microbial pathogens due in part to the timing of expression. In this paper, we will explore the current understanding of chemokine production as it relates to the orchestration of the immune response to HSV infection.
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PMID:Herpes simplex virus and the chemokines that mediate the inflammation. 1657 Aug 56


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