Latent TGF-beta 1 binding protein (LTBP-1): a new marker for intra- and extraocular PEX deposits

Background: Pseudoexfoliation (PEX) syndrome is a generalized process of th e extracellular matrix characterized by the accumulation of an abnormal pat hognomonic material in various intraocular and extraocular tissues. Whereas the intraocular manifestations can be directly diagnosed by biomicroscopic observations, the extraocular manifestations can presently only be diagnos ed by electron microscopic methodology. in order to better evaluate the dis tribution and precise localization of PEX deposits in the various organ sys tems, we searched for a relatively specific immunohistochemical marker for PEX material on the light microscopic level. Material and Methods: Eyes and tissue specimens of various organ systems (s kin, heart, lungs, liver, kidney abdominal aorta, cerebral artery, plexus c horoideus, meninges) obtained from 4 organ donors with ocular PEX syndrome and age-matched control tissues were investigated by electron microscopy an d immunohistochemistry using antibodies against various elastic microfibril lar components. Results: Out of a panel of antibodies tested, the immunolabeling of both in tra- and extraocular PEX deposits with antibodies against. latent TGF-beta 1 binding protein (LTBP-1) was particularly prominent. In addition to the k nown intraocular sites of PEX material accumulations, focal plaque-like LIB P-1 positive deposits could be observed in the conjunctival stroma, optic n erve meninges, skin, heart muscle. lungs, kidney as well as in the adventit ia of the aorta and cerebral artery from donors with PEX syndrome; such pla que-like deposits positive for LTBP-1 were not present in the control tissu es. Transmission electron microscopy confirmed the presence of typical fibr illar PEX aggregates in the respective tissues. Conclusions: Antibodies against LTBP-1 provide a new and relatively specifi c marker for PEX deposits both in intraocular and extraocular locations. Sy stematic screening of PEX accumulations in a larger number of extraocular t issue specimens obtained from PEX patients may help to elucidate the functi onal implications and consequences of the systemic manifestations.