Background: Pseudoexfoliation (PEX) syndrome is a generalized process of the extracellular matrix characterized by the accumulation of an abnormal pathognomonic 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 diagnosed by electron microscopic methodology. In order to better evaluate the distribution and precise localization of PEX deposits in the various organ systems, 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 (skin, heart, lungs, liver, kidney, abdominal aorta, cerebral artery, plexus choroideus, meninges) obtained from 4 organ donors with ocular PEX syndrome and age-matched control tissues were investigated by electron microscopy and immunohistochemistry using antibodies against various elastic microfibrillar components.
Results: Out of a panel of antibodies tested, the immunolabeling of both intra- and extraocular PEX deposits with antibodies against latent TGF-beta 1 binding protein (LTBP-1) was particularly prominent. In addition to the known intraocular sites of PEX material accumulations, focal plaque-like LTBP-1 positive deposits could be observed in the conjunctival stroma, optic nerve meninges, skin, heart muscle, lungs, kidney as well as in the adventitia of the aorta and cerebral artery from donors with PEX syndrome; such plaque-like deposits positive for LTBP-1 were not present in the control tissues. Transmission electron microscopy confirmed the presence of typical fibrillar PEX aggregates in the respective tissues.
Conclusions: Antibodies against LTBP-1 provide a new and relatively specific marker for PEX deposits both in intraocular and extraocular locations. Systematic screening of PEX accumulations in a larger number of extraocular tissue specimens obtained from PEX patients may help to elucidate the functional implications and consequences of the systemic manifestations.