FIBRILLIN-1 GENE EXPRESSION IN PSEUDOEXFOLIATION SYNDROME: A PATHOGENETIC CONCEPT
U. Schlötzer-Schrehardt, K. von der Mark, M. Küchle, C. Rummelt, G.O.H. Naumann
The pseudoexfoliation (PEX) syndrome is now recognized as a generalized disorder of the extracellular matrix leading to accumulation of a pathognomonic matrix product in intra- and extraocular tissues. To elucidate the still unknown pathogenesis we analyzed the characteristic matrix disturbance of the cells involved in a molecular biologic approach.
Methods: The glycoprotein fibrillin-1, the main component of elastic microfibrils, has proved to be an integral constituent of PEX fibers in previous studies. The expression of cytoplasmic fibrillin-1 mRNA was therefore investigated by in situ hybridization using non- radioactively labeled riboprobes for fibrillin-1 on tissue sections of intra- and extraocular tissues from patients with and without PEX syndrome. Fluorescence or chromogenic markers were used for signal detection.
Results: In situ hybridization analysis revealed no message for fibrillin-1 in ocular and extraocular control tissues without PEX. Expression of fibrillin-1 mRNA could, however, be focally detected in the preequatorial lens epithelium, the nonpigmented ciliary epithelium, fibroblasts and vascular endothelial cells of the iris stroma, endothelial cells of Schlemms canal in the trabecular meshwork as well as in conjunctival and dermal fibroblasts of PEX patients. The signals were in consistence with the immunohisto- chemical localization of fibrillin-1 positive PEX fibers on lens and ciliary body, in iris stroma and trabecular meshwork, and in connective tissue stroma of conjunctiva and eyelid-skin.
Conclusion: Molecular biologic and immunohistochemical evidence substantiates the concept of PEX syndrome as a disorder of elastic microfibrils associated with an enhanced expression of fibrillin mRNA and excessive production of fibrillin-positive PEX fibers.
supported by the Deutsche Forschungsgemeinschaft (SFB 539)
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