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Role of Endothelin-1 in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Schlötzer-Schrehardt U., Küchle M., Jünemann A., Naumann G. O. H.,
Friedrich-Alexander-Universität, Augenklinik (Erlangen)

Purpose: Pseudoexfoliation (PEX) syndrome represents an important risk factor for glaucoma and for ocular and systemic vascular complications. Because the endothelin (ET) system is crucially involved in the regulation of perfusion and intraocular pressure, we investigated the role of ET-1, a potent vasoconstrictor, and its specific receptors ETA and ETB in the pathogenesis of PEX syndrome and PEX glaucoma.
Methods: The concentration of ET-1 in aqueous humor and plasma from 20 patients with PEX syndrome, PEX glaucoma, primary open-angle glaucoma (POAG), and cataract, respectively, was measured using an immunoassay; the protein expression of ET-1, ETA, and ETB in ocular tissues from PEX and control patients was analysed by immunohistochemistry.
Results: Whereas the plasma levels of ET-1 (1.4-1.7 pg/ml) showed no significant differences, the aqueous levels of ET-1 were significantly increased in patients with PEX syndrome (9.4±3.5 pg/ml), PEX glaucoma (12.7±3.9 pg/ml), and POAG (13.4±4.2 pg/ml) as compared to patients with cataract (6.5±1.3 pg/ml). ET-1 could be immunolocalized in all ocular tissues, particularly in vascular endothelial cells and smooth muscle cells, but also in trabecular endothelial and ciliary epithelial cells. ETA and ETB receptors showed a widespread but differential expression in ocular tissues with a predominant cytoplasmic localization of ETA and a mainly nuclear association of ETB. In PEX eyes, a markedly increased immunoreaction of ET-1 and both receptor subtypes was observed in the iris stroma and in the walls of iris vessels.
Conclusions: Whereas no relationship could be established between plasma levels of ET-1 and cardiovascular complications in PEX patients, the significantly elevated levels of ET-1 in the aqueous humor and the increased expression of ET-1 and its receptors in the iris of patients with PEX syndrome/glaucoma may be causally involved in the development of both PEX-associated glaucoma and iris vasculopathy in these patients.