LTBR Ig preserved the integrity of the ocular surface The integrity of the ocular epithelial surface serves as an indirect measure of the long term EPZ-5676 mw consequences of net changes in the protein composition of the tear film, in combination with the rate volume of tear fluid secretion. Application of aqueous FITC is a simple and effective way to assess the condition of the ocular surface. In this analysis, perfectly intact epithelium does not bind FITC. In contrast, defects in the ocular surface epithelial cell layer allow FITC to access components of the underly ing cell layers and extra cellular matrix where the FITC then can adhere and is visible under UV enriched illu mination with a cobalt blue filter.

Using an established, semi quantitative scoring system, FITC staining of the corneal conjunctival surface was Inhibitors,Modulators,Libraries evaluated by slit lamp microscopic eye examination of each eye, and the corneal and conjunctival areas were scored on a scale of 1 to 4 by an observer unaware of the type of treatment given to each mouse. Inhibitors,Modulators,Libraries The cornea was defined as the region directly over the center of the eye and extending to the peri meter of the pupil, and the con junctiva was the remainder of the ocular surface. Selected examples of the extremes of the range of FITC staining are shown in Figure 7a, in which a zero score is illustrated with an LTBR Ig treated mouse and Inhibitors,Modulators,Libraries a maxi mal score of 4 is illustrated with an untreated mouse. As shown in Figure 7b, LTBR Ig treatment of mice for 8 weeks resulted in significantly lower scores for FITC staining for both conjunctiva and cornea, reflecting less damage to the ocular epithe lial surface.

Discussion In this study, antagonism of the LTBR axis greatly reduced CXCL13 in diseased extra orbital lacrimal glands and profoundly reduced the B lymphocyte bur den in the glands. These effects of LTBR antagonism on B cells and CXCL13 are especially interesting in light of the recent recognition of the importance of B cells in Sj?grens syndrome. Certain Inhibitors,Modulators,Libraries B cell subsets found in the glands of Sj?grens patients, possibly due to aberrant expression of B cell growth and differentiation factor BAFF, have been proposed to contribute to the patho Inhibitors,Modulators,Libraries genesis in Sj?grens. That B cells contribute greatly to other autoimmune diseases has been verified clinically, as exemplified by the success of B cell deple tion therapy for treatment of rheumatoid arthritis.

Recently, a report of a double blind, randomized clinical trial of B cell depletion by rituximab showed beneficial effects in Sj?grens patients suggesting that B cell tar geted therapies may be useful to treat Sj?grens syn drome as well. The health cisplatin synthesis of the ocular surface depends on diverse factors, including tear osmolarity, the protein proteogly can constituents of tear fluids, and the volume of tear fluid delivered to the ocular surface.