The proposal is a continuation of the PI's ongoing studies ont he role of corneal lipids in inflammation. The PI has discovered that the lipid mediator, platelet-activating factor (PAF) induces the expression of enzymes involved in the degradation of extracellular matrix (ECM) components such as the metalloproteinases (MMP)-1 and MMP-g and of urokinase plasminogen activator (uPA), as well as the induction of the expression of the proinflammatory cyclooxygenase-2 (COX-2) and increased synthesis of prostaglandins (PGs). The specific messengers involved in these events are not known. The PI proposes experiments to test if, during a prolonged inflammatory process: 1)PGs stimulated by PAF can, but autocrine and paracrine mechanisms, activate MMPs and uPA in epithelial and stromal cells; and mechanisms which promote stimulation in ECM degradation and contribute to corneal ulcer formation. When inflammation is not sustained, specific lipids can have a role in the tissue repair process. The hypothesis is that PAF, through the activation of tyrosine kinases, stimulates a signaling pathway involved in epithelial cell migration and wound closure, while the lipoxygenase metabolite, 12(S)-HETE, is an intermediate to epidermal growth factor response in its proliferative action. Selective COX-2 and lipoxygenase inhibitors, as well as PAF antagonists, will be evaluated to determine their sites of action and to correlate their biochemical effects with the clinical evaluation of wound healing or ulcer formation. Quantification of specific mRNA will be accomplished by Northern blot and quantitative pCR. identification of pathway components will be done by RP-HPLC, Western blot and immunprecipitation, as well as Ca2+ imaging. The results obtained will define the involvement of PAF, PGs and 12(s)-HETE in corneal damage and repair and allows us to characterize drugs that target selective steps in the corneal inflammatory response.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004928-20
Application #
6518326
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Shen, Grace L
Project Start
1983-07-01
Project End
2003-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
20
Fiscal Year
2002
Total Cost
$203,086
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
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He, Jiucheng; Eastlack, Jason P; Bazan, Haydee E P (2010) The induction of an angiogenic response in corneal myofibroblasts by platelet-activating factor (PAF). Curr Eye Res 35:1063-71

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