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

Following ocular HSV-1 infection, neovascularisation of the avascular cornea is a critical event in the pathogenesis of herpetic stromal keratitis. This present study evaluates the role of proinflammatory cytokines such as IL-6 in corneal angiogenesis following virus infection. Both in vivo and in vitro data indicate that IL-6 produced from virus-infected cells can stimulate noninfected resident corneal cells and other inflammatory cells in a paracrine manner to secrete VEGF, a potent angiogenic factor. Antibody neutralisation of IL-6 resulted in a significant decrease in the number of VEGF producing cells in the cornea. Thus, our results further demonstrate the close relationship between proinflammatory cytokines and VEGF-induced corneal neovascularisation.
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PMID:Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection. 1600 63

Diabetes Mellitus (DM) is a serious medical problem that causes long-term systemic complications and considerable associated morbidity. DM can cause retinopathy (DRP), maculopathy, cataract, optic neuropathy, defects of eye muscles. DM is a risk factor for acute infectious conjunctivitis, bacterial keratitis, herpes virus infections and endophtalmitis. Elevated blood glucose induces structural, physiological and hormonal changes which affect retinal capillaries. DRP is recognized by loss of pericyte function and capillary occlusions together leading to breakdown of blood-retinal barrier, edematous changes and proliferation of vessels and fibrous tissue. Depending on stage of DRP, there are different preferable therapeutic approaches applied. In the case of ETDRS, in the area of leakage focal treatment should be performed, while panretinal photocoagulation is applied towards ischemic areas or beginning proliferations. Vitreal haemorrhage followed by fibroproliferative changes or tractional retinal detachment is treated by vitrectomy alone or in combination with ILM peeling. In pathogenesis of DRP, Insulin Growth Factor (IGF-1) can play an important role in production of VEGF (Vascular Endothelial Growth Factor). Hypoxia can up-regulate VEGF expression levels leading to pathologic ocular neovascularisation. An application of intravitreal corticosteroid treatment modulates vascular permeability by suppressing the production of VEGF, reducing both extracellular matrix metalloproteinase activity and basic fibroblast growth factor, decreasing major histocompatibility complex 2 Ag expression levels, and inhibiting activity of inflammatory cells. Clinical effects of treatment using intravitreal corticosteroids are evaluated by reduction of macular thickness and visual improvement. Intravitreal use of Anti-VEGF drugs, Pegaptanib, Ranibizumab and Bevacizumab can modify vasoproliferation, trigger macular edema, and, therefore, influence a prognosis for visual loss.
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PMID:Eye disorders in diabetes: potential drug targets. 1853 2

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). VEGF was elevated in HCRF and THP-1 following treatment with HSV-DNA and HSV-IC. MMP-9 was elevated in THP-1 but not in corneal cells. When anti-HSV-IgG(Fab')2 complexes stimulated THP-1, MMP-9 was reduced to control levels. Pretreatment of THP-1 with anti-TLR-2 and -3 inhibited MMP-9 production. Thus, HSV-IC may stimulate THP-1 through the Fc receptor and TLRs. Proinflammatory cytokines (IL-1b, IL-6, and TNF-alpha) increased VEGF and MMP-9 in corneal cells and macrophages. These studies indicate that the continued presence of HSV-DNA and HSV-IC contribute to angiogenesis and inflammation in HSK. Thus, cytokines and TLRs may be potential targets for intervention.
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PMID:HSV immune complex (HSV-IgG: IC) and HSV-DNA elicit the production of angiogenic factor VEGF and MMP-9. 1911 32

The normal cornea is transparent, which is essential for normal vision, and although the angiogenic factor vascular endothelial growth factor A (VEGF-A) is present in the cornea, its angiogenic activity is impeded by being bound to a soluble form of the VEGF receptor-1 (sVR-1). This report investigates the effect on the balance between VEGF-A and sVR-1 that occurs after ocular infection with HSV, which causes prominent neovascularization, an essential step in the pathogenesis of the vision-impairing lesion, stromal keratitis. We demonstrate that HSV-1 infection causes increased production of VEGF-A but reduces sVR-1 levels, resulting in an imbalance of VEGF-A and sVR-1 levels in ocular tissues. Moreover, the sVR-1 protein made was degraded by the metalloproteinase (MMP) enzymes MMP-2, -7, and -9 produced by infiltrating inflammatory cells that were principally neutrophils. Inhibition of neutrophils, inhibition of sVR-1 breakdown with the MMP inhibitor marimastat, and the provision of exogenous recombinant sVR-1 protein all resulted in reduced angiogenesis. Our results make the novel observation that ocular neovascularization resulting from HSV infection involves a change in the balance between VEGF-A and its soluble inhibitory receptor. Future therapies aimed to increase the production and activity of sVR-1 protein could benefit the management of stromal keratitis, an important cause of human blindness.
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PMID:Ocular neovascularization caused by herpes simplex virus type 1 infection results from breakdown of binding between vascular endothelial growth factor A and its soluble receptor. 2132 21

Ocular infection with HSV causes corneal neovascularization (CV), an essential step in the pathogenesis of the blinding immunoinflammatory lesion stromal keratitis. The infection results in IL-17A production, which contributes to CV in ways that together serve to shift the balance between corneal concentrations of vascular endothelial growth factor A (VEGF-A) and the soluble vascular endothelial growth factor receptor 1 molecule, which binds to VEGF-A and blocks its function (a so-called VEGF trap). Accordingly, animals lacking responses to IL-17A signaling, either because of IL-17 receptor A knockout or wild-type animals that received neutralizing mAb to IL-17A, had diminished CV, compared with controls. The procedures reduced VEGF-A protein levels but had no effect on the levels of soluble vascular endothelial growth factor receptor 1. Hence the VEGF trap was strengthened. IL-17A also caused increased CXCL1/KC synthesis, which attracts neutrophils to the inflammatory site. Neutrophils further influenced the extent of CV by acting as an additional source of VEGF-A, as did metalloproteinase enzymes that degrade the soluble receptor, inhibiting its VEGF-blocking activity. Our results indicate that suppressing the expression of IL-17A, or increasing the activity of the VEGF trap, represents a useful approach to inhibiting CV and the control of an ocular lesion that is an important cause of human blindness.
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PMID:IL-17A differentially regulates corneal vascular endothelial growth factor (VEGF)-A and soluble VEGF receptor 1 expression and promotes corneal angiogenesis after herpes simplex virus infection. 2237 30

The cornea is a complex sensory organ that must maintain its transparency for optimal vision. Infections such as with herpes simplex virus can result in blinding immunoinflammatory reactions referred to as herpes stromal keratitis (HSK). In this review we discuss the pathogenesis of HSK referring to work mainly done using animal model systems. We briefly discuss the role of multiple cell types and soluble mediators but focus on the critical role of corneal vascularization (CV) in contributing to corneal damage. We describe how VEGF and other angiogenic molecules are induced following infection and discuss the many ways by which CV can be controlled. Speculations are made regarding future approaches that could improve the management of HSK.
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PMID:Pathogenesis of herpes stromal keratitis--a focus on corneal neovascularization. 2289 44

Meliacine (MA), an antiviral principle present in partially purified leaf extracts of Melia azedarach L., reduces viral load and abolishes the inflammatory reaction and neovascularization during the development of herpetic stromal keratitis in mice. 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), obtained from MA, displays anti-herpetic and immunomodulatory activities in vitro. We investigated whether CDM interferes with the angiogenic process. CDM impeded VEGF transcription in LPS-stimulated and HSV-1-infected cells. It proved to have neither cytotoxic nor antiproliferative effect in HUVEC and to restrain HUVEC migration and formation of capillary-like tubes. Moreover, MA inhibits LMM3 tumor-induced neovascularization in vivo. We postulate that the antiangiogenic activity of CDM displayed in vitro as a consequence of their immunomodulatory properties is responsible for the antiangiogenic activity of MA in vivo, which would be associated with the lack of neovascularization in murine HSV-1-induced ocular disease.
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PMID:A natural antiviral and immunomodulatory compound with antiangiogenic properties. 2300 4

In order to showcase the major research advances in ophthalmology of the recent five years (2009-2013) in China, the 11th Committee of the Ophthalmic Division of Chinese Medical Association launched the selection of Top Ten Research Advances of Ophthalmology in China. Each ophthalmic subspecialty group voted its top ten research advances and chose two out of ten to join the selection. The Committee voted top ten out from all candidates and announced the final result with honor. The following research advances were selected as the Top Ten Research Advances of Ophthalmology in China: Innovative theory and its application of fungal keratitis; Increased gradient pressure between IOP and ICP is the main cause of glaucomatous optic neuropathy; Domestic developed anti-VEGF medicine Conbercept has been applied successfully in the treatment of choriodal neovascularization; IL-23/IL-17 pathway and their regulation in the pathogenesis of uveitis; The creation of myopic animal model and the biochemical mechanism of myopia; Specialists' consensus on diagnosing amblyopia in children; Generation of induced pluripotent stem cells from human fibroblasts of the Tenon's capsule; The development and application of endoscopic navigation system in orbital surgery; Studies of pathogenesis on congenital cataract candidate gene mutations; The regulation for the diagnosis and treatment of pediatric retinal diseases in China and its extension.
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PMID:[Top ten research advances of ophthalmology in China (2009-2013)]. 2538 81

A 7-year-old, 153.0-kg American Miniature mare presented for evaluation of keratoconjunctivitis of the right eye (OD). A superior palpebral conjunctival mass and stromal keratitis were diagnosed. The incisional biopsy diagnosis was a presumptive corneal hemangiosarcoma. Transpalpebral enucleation was performed, and histopathologic evaluation confirmed angiosarcoma of the conjunctiva, cornea, and extraocular muscles. The horse developed progressive epistaxis and orbital swelling following surgery. A systemic workup was performed 3 months after enucleation, revealing regrowth within the orbit and marked cranial cervical lymphomegaly, suggestive of metastasis. Humane euthanasia was performed, and necropsy confirmed a locally invasive periorbital tumor with metastasis to the submandibular tissue, submandibular lymph node, and thoracic inlet. Histopathologic evaluation of necropsy specimens revealed polygonal to spindle neoplastic cells lining neoplastic vascular channels lacking erythrocytes. Immunohistochemically, the neoplastic cells labeled strongly positive for PROX-1, vimentin, CD-31, VEGF, weakly positive for factor VIII-related antigen, and negative for collagen IV. Based on the clinical, histological, and immunohistochemical features of this tumor, a primary ocular lymphangiosarcoma with metastasis was diagnosed.
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PMID:Presumed primary ocular lymphangiosarcoma with metastasis in a miniature horse. 2558 59

The cornea is a complex tissue that must preserve its transparency to maintain optimal vision. However, in some circumstances, damage to the eye can result in neovascularization that impairs vision. This outcome can occur when herpes simplex virus type 1 (HSV-1) causes the immunoinflammatory lesion stromal keratitis (SK). Potentially useful measures to control the severity of SK are to target angiogenesis which with herpetic SK invariably involves VEGF. One such way to control angiogenesis involves the endothelial receptor Robo4 (R4), which upon interaction with another protein activates an antiangiogenic pathway that counteracts VEGF downstream signaling. In this study we show that mice unable to produce R4 because of gene knockout developed significantly higher angiogenesis after HSV-1 ocular infection than did infected wild type (WT) controls. Moreover, providing additional soluble R4 (sR4) protein by subconjunctival administration to R4 KO HSV-1 infected mice substantially rescued the WT phenotype. Finally, administration of sR4 to WT HSV-1 infected mice diminished the extent of corneal angiogenesis compared to WT control animals. Our results indicate that sR4 could represent a useful therapeutic tool to counteract corneal angiogenesis and help control the severity of SK.
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PMID:Robo 4 Counteracts Angiogenesis in Herpetic Stromal Keratitis. 2672 Jan 97


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