BETA-AMYLOID PROTEIN-PRECURSOR EXPRESSION IN LACRIMAL GLANDS AND TEARFLUID

Purpose. Proteases in tear fluid play important roles in the regulatio n of corneal wound healing. Inhibitors of proteolytic activity are maj or modulators of the associated events. Although it is known that vari ous enzyme inhibitors exist in tear fluid, it is not known whether cer tain isoforms of the beta-amyloid protein precursor (beta-APP), a pote nt inhibitor of serine proteases, are present in tear fluid. The purpo se of this study was to investigate whether beta-APP can be detected i n human tear fluid and, if so, to determine the isoform composition an d cellular origin. Methods. Tear fluid was collected from healthy volu nteers. The beta-APP was identified and characterized by immunoblottin g using antibodies specific for domains of the beta-APP. The protein w as characterized further by ion exchange chromatography. Expression of the beta-APP gene was studied using in situ hybridization and RNA-RNA solution hybridization assay. Results. beta-APP with protease inhibit ory properties was identified in all samples of human tear fluid. Immu nologic analysis revealed that it had been processed proteolytically b efore secretion. Gene expression studies showed that the beta-APP gene was expressed in lacrimal glands, particularly in acinar cells. The g ene transcript almost exclusively corresponded to beta-APP containing the protease inhibitor insert. Conclusions. beta-APP is expressed in l acrimal glands and subsequently is secreted into tear fluid. Because t he bulk of the beta-APP contained the protease inhibitor insert, the a uthors propose that beta-APP is an important regulator of proteolysis in tear fluid and that possibly it plays a role in the events associat ed with corneal wound healing. This suggests a novel physiological fun ction of beta-APP in addition to those previously described-regulation of blood coagulation and cell growth.