Lacrimal gland acinar cells secrete an important array of bacteriocidal tear proteins that are critical for the health of the ocular surface. 'BM180', a recently discovered component of the lacrimal peri-acinar basement membrane, appears to play an important role in modulating tear protein secretion. The goal of this proposal is to characterize BM180 and establish whether it is linked to the Dry Eye component of Sjogren's syndrome. The exorbital lacrimal gland, located adjacent to the eye in its superior lateral aspect, contains a vast number of basement membranes which appear in cross-section as linear peri-acinar structures. The PI searched for basement membrane molecules which interact with lacrimal and parotid glands.
The specific aims of this proposal are: (i) to complete the cDNA cloning of BM180; (ii) to prepare recombinant BM180 for elucidation of site(s) in BM180 responsible for modulating tear secretion, the BM180 receptor and how BM180 affects intracellular signalling; and (iii) to establish the incidence and pathogenicity of anti-BM180 autoantibodies in Sjogren s syndrome patients. The approach is to use a PCR-based cloning strategy, combined with a eukaryotic expression system, to unveil molecular mechanisms of BM180 action. These studies could open the door to a new molecular understanding of Dry Eye in Sjogren's syndrome and lead to new therapeutic strategies.
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