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)

Corneal neovascularization (CNV) can cause significant visual loss because of the scarring and lipid deposition that frequently accompany it. In addition, penetrating keratoplasty in a vascularized recipient carries a significant risk of failure from allograft rejection. Frequently CNV is induced by nonspecific inflammatory stimuli, mediated primarily by polymorphonuclear neutrophils. Neovascularization can also be associated with specific corneal immune reactions, such as herpes simplex keratitis. Immunologically mediated CNV may be more amenable to treatment than CNV that results from nonspecific inflammation. Photodynamic therapy (PDT) following the intravenous injection of hematoporphyrin derivative or purified dihematoporphyrin ether (DHE) has been shown to suppress tumor growth and blood vessel growth in the eye. We have developed a murine model of CNV induced by the intrastromal injection of stimulated lymphocytes or interleukin-2 (IL-2). We have noted corneal DHE retention following its intravenous injection in mice with IL-2 induced CNV. Preliminary studies indicate that PDT can induce regression of CNV in these mice. Other recent studies that have enhanced our understanding of the pathogenesis and treatment of CNV are reviewed, and directions for future research are discussed.
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PMID:Corneal neovascularization. Pathogenesis and inhibition. 244 23

In herpetic keratitis, the role of T cell subsets is not clearly understood although the involvement of cell-mediated immunity has been reported. The purpose of this paper is to analyse T cell-mediated immunopathological conditions and the role of non-T cell lineage in herpetic stromal keratitis employing nude (nu/nu) and Balb/c mice. All mice were divided into three groups. Group 1: Herpes simplex virus type 1 (HSV-1)-inoculated nu/nu mice. Group 2: HSV-1-inoculated nu/nu mice with interleukin-2 (IL-2). Group 3: HSV-1-inoculated Balb/c mice. The conditions of the disease were compared in those three groups clinically and by using histological and immunopathological staining. Following antibodies were employed: anti-Asialo GMI (natural killer). anti-Thy 1 (pan-T). anti-L3T4 (helper/inducer), anti-Lyt 2 (suppressor/killer), anti-Mac 3 (macrophage), anti-Mice Immunoglobulins (monocyte. B.). Corneal lesions showed a reduced inflammatory tendency in nu/nu mice. Topical application of IL-2 in nu/nu mice induced moderate stromal inflammation compared with nu/nu mice. However, the severity of these was less than in Balb/c. Many natural killer cells (NK) were found in nu/nu mice but few in Balb/c mice. These results confirm the involvement of T-cell mediated immunity in stromal inflammation and indicate that NK cell may have an important role in suppressed T-cell immunity in nu/nu mice but are not involved in stromal inflammation.
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PMID:[Immunopathological analysis of T and non-T cell involvement in corneal inflammation caused by HSV type-1 infection]. 278 89

Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) may be an important mediator in the blinding ocular inflammation which develops following herpes simplex virus type 1 (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP-1alpha-deficient (-/-) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 x 10(5) PFU of HSV-1 strain RE and subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the mean corneal opacity score of -/- mice was 1.1 +/- 0.3 while that of the +/+ mice was 3.7 +/- 0.5. No detectable infiltrating CD4+ T cells were seen histologically at 14 or 21 days p.i. in -/- animals, whereas the mean CD4+ T-cell count per field (36 fields counted) in +/+ hosts was 26 +/- 2 (P < 0.001). In addition, neutrophil counts in the -/- mouse corneas were reduced by >80% in comparison to the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon could be detected in six of seven -/- mice, whereas both T-cell cytokines were readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte chemoattractant protein-1 protein levels were significantly lower in MIP-1alpha -/- mouse corneas than in +/+ host corneas, suggesting that MIP-1alpha directly, or more likely indirectly, influences the expression of other chemokines. Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from the eyes of -/- mice was not significantly different from that observed in +/+ hosts. We conclude that MIP-1alpha is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis.
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PMID:Absence of macrophage inflammatory protein-1alpha prevents the development of blinding herpes stromal keratitis. 955 52

Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. Sprague-Dawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunized rats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunized groups had significantly reduced IL-1 beta levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adverse pathology, with nasal immunization being the most effective.
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PMID:Effector mechanisms of protection against Pseudomonas aeruginosa keratitis in immunized rats. 1129 52

Generating and using regulatory T cells (Tregs) to modulate inflammatory disease represents a valuable approach to therapy but has not yet been applied as a means to control virus-induced immunopathological reactions. In this report, we developed a simplified technique that used unfractionated splenocytes as a precursor population and showed that stimulation under optimized conditions for 5 days with solid-phase anti-CD3 monoclonal antibody in the presence of transforming growth factor beta (TGF-beta) and interleukin-2 could induce up to 90% of CD4(+) T cells to become Foxp3(+) and able to mediate suppression in vitro. CD11c(+) dendritic cells were intricately involved in the conversion process and, once modified in the presence of TGF-beta, could convert Foxp3(-) CD4(+) cells into Foxp3(+) CD4(+)cells by producing TGF-beta. The converted cells had undergone cell division, and the majority of them expressed activation markers along with surface molecules that would facilitate their migration into tissue sites. The primary reason for our study was to determine if such in vitro-converted Tregs could be used in vivo to influence the outcome of a virus-induced immunoinflammatory lesion in the eye caused by herpes simplex virus infection. We could show in three separate models of herpetic stromal keratitis that adoptive transfers of in vitro-converted Tregs effectively diminished lesion severity, especially when given in the initial phases of infection. The suppression effect in vivo appeared to be polyspecific. The protocol we have developed could provide a useful additional approach to control virus-induced inflammatory disease.
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PMID:In vitro-generated antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells control the severity of herpes simplex virus-induced ocular immunoinflammatory lesions. 1848 Apr 41