The process of leukocyte migration across the vascular endothelial barrier is fundamental to the process of inflammation and the response to infection. We will quantitate the effect of various medications such as topical corticosteroids, oral nonsteroidal anti-inflammatory drugs, and mast cell stabilizers in several of these processes. We have applied intravital microscopy in animal systems to visualize, quantitate and analyze this process. Recent advances in confocal microscopy have allowed a European group to quantitate leukocyte endothelial rolling and sticking in the microvasculature of the human eye. Combining our clinical expertise in confocal microscopy and our experience analyzing leukocyte vascular interactions, we propose to utilize in vivo confocal technology to quantitate leukocyte rolling and arrest in 4 different human vascular beds: the limbus, conjuctiva, episclera, and sclera. With these three specific aims:
Aim one, we propose to image rolling and sticking of leukocytes in four different normal ocular vascular beds: the conjunctiva, limbus, episclera, and sclera.
Aim two, we will compare leukocyte-endothelial dynamics in specific vascular beds in seven disease states: a) allergic seasonal conjunctivitis, b) Sjogren's syndrome and dry eye, c) blepharitis, d) graft versus host disease (GVHD), e) episcleritis, f) scleritis, and g) anterior uveitis.
Aim three, we will determine the effect of medications including topical prednisolone acetate, a mast cell stabilizer (optipranolol), or an oral nonsteroidal anti-inflammatory drug (indomethacin) on endothelial-leukocyte dynamics in diseases for which each is frequently prescribed. Our studies will directly clarify the pathogenesis of several troublesome and rarely studied ocular disease processes. These studies will elucidate the mechanism by which medications alter these processes. Most importantly these studies will quantitate a fundamental human biological process in microvascular beds that have not previously been imaged. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
5R03EY014013-02
Application #
6732733
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Fisher, Richard S
Project Start
2003-04-15
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$148,450
Indirect Cost
Name
Oregon Health and Science University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Wertheim, Michael S; Mathers, William D; Lim, Lyndell et al. (2006) Non-invasive detection of multinucleated giant cells in the conjunctiva of patients with sarcoidosis by in-vivo confocal microscopy. Ocul Immunol Inflamm 14:203-6
Wertheim, Michael S; Mathers, William D; Suhler, Eric B et al. (2005) Histopathological features of conjunctival sarcoid nodules using noninvasive in vivo confocal microscopy. Arch Ophthalmol 123:274-6
Wertheim, Michael S; Mathers, William D; Planck, Stephen J et al. (2004) In vivo confocal microscopy of keratic precipitates. Arch Ophthalmol 122:1773-81