YEARS

2003-2005

AUTHORS

A. Razzaque Ahmed

TITLE

Fibrogenic factors in ocular cicatricial pemphigoid

ABSTRACT

DESCRIPTION (provided by applicant): The long-term objective of this grant application is to study the molecular mechanism of scarring in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Severe conjunctival scarring leads to blindness in about 25% of OCP patients, inspite of aggressive systemic therapy. The aim of this grant proposal is to identify some of the factors that are involved in the inflammatory and fibrotic stages, and define their role in the scarring process. Investigators studying ocular scarring in toxic epidermolysis necrosis, Steven-Johnson syndrome, epidermolysis bullosa acquisita, and other similar diseases will significantly benefit from these experiments. The PI has focused on only few molecules in an attempt to define a model system. Our preliminary studies suggest an important role for macrophage colony-stimulating factor (m-CSF), transforming growth factor (TGF)-beta1, matrix metalloproteases (MMPs), and tissue inhibitors of metalloproteases (TIMPs) in regulating inflammatory and fibrotic events in the conjunctiva of OCP patients, and in fibroblasts isolated from conjunctiva of OCP patients. In our proposed study, we will determine the role of macrophage-recruiting molecules, isoforms of TGF-beta, connective tissue growth factor (CTFG), specific members of MMPs and TIMPs (as determined by our microarray analysis) in conjunctiva of patients with OCP. We will perform in vivo studies using an established mouse model of conjunctival scarring to determine the effects of blocking CTGF in this model. We anticipate that the results from studies proposed in this grant application will provide information that will identify and describe some of the key molecules that influence conjunctival scarring in patients with OCP. The studies have significant therapeutic potential. The identified molecules or portion of processes that mediate could be blocked or arrested, and this may result in cessation of disease progression and, prevention of blindness.

FUNDED PUBLICATIONS

  • Role of macrophage migration inhibitory factor in conjunctival pathology in ocular cicatricial pemphigoid.
  • Relationship between cancer and oral pemphigoid patients with antibodies to alpha6-integrin.
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    19 TRIPLES      17 PREDICATES      20 URIs      9 LITERALS

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    1 grants:a4df4cc4b65f2aa039245b3c547ac4ff sg:abstract DESCRIPTION (provided by applicant): The long-term objective of this grant application is to study the molecular mechanism of scarring in the conjunctiva of patients with ocular cicatricial pemphigoid (OCP). Severe conjunctival scarring leads to blindness in about 25% of OCP patients, inspite of aggressive systemic therapy. The aim of this grant proposal is to identify some of the factors that are involved in the inflammatory and fibrotic stages, and define their role in the scarring process. Investigators studying ocular scarring in toxic epidermolysis necrosis, Steven-Johnson syndrome, epidermolysis bullosa acquisita, and other similar diseases will significantly benefit from these experiments. The PI has focused on only few molecules in an attempt to define a model system. Our preliminary studies suggest an important role for macrophage colony-stimulating factor (m-CSF), transforming growth factor (TGF)-beta1, matrix metalloproteases (MMPs), and tissue inhibitors of metalloproteases (TIMPs) in regulating inflammatory and fibrotic events in the conjunctiva of OCP patients, and in fibroblasts isolated from conjunctiva of OCP patients. In our proposed study, we will determine the role of macrophage-recruiting molecules, isoforms of TGF-beta, connective tissue growth factor (CTFG), specific members of MMPs and TIMPs (as determined by our microarray analysis) in conjunctiva of patients with OCP. We will perform in vivo studies using an established mouse model of conjunctival scarring to determine the effects of blocking CTGF in this model. We anticipate that the results from studies proposed in this grant application will provide information that will identify and describe some of the key molecules that influence conjunctival scarring in patients with OCP. The studies have significant therapeutic potential. The identified molecules or portion of processes that mediate could be blocked or arrested, and this may result in cessation of disease progression and, prevention of blindness.
    2 sg:endYear 2005
    3 sg:fundingAmount 739247.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:15b0243dd142977e7ccae0277704762a
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    8 sg:hasFundedPublication articles:ba14b32cc7b2bc84913e1ce66875eeba
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    11 sg:hasRecipientOrganization grid-institutes:grid.38142.3c
    12 sg:language English
    13 sg:license http://scigraph.springernature.com/explorer/license/
    14 sg:scigraphId a4df4cc4b65f2aa039245b3c547ac4ff
    15 sg:startYear 2003
    16 sg:title Fibrogenic factors in ocular cicatricial pemphigoid
    17 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=6792622
    18 rdf:type sg:Grant
    19 rdfs:label Grant: Fibrogenic factors in ocular cicatricial pemphigoid
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