The composition of exfoliation material and the cells involved in its production.

Abstract

The hallmark of exfoliation syndrome is the pathologic production and stable accumulation of an abnormal, fibrillar, extracellular material (XFM). Although the exact biochemical composition of the pathologic matrix product is still not known, immunohistochemical and biochemical approaches have shown XFM to represent a highly glycosylated, cross-linked, and enzymatically resistant glycoprotein/proteoglycan complex, composed of a protein core surrounded by glycoconjugates. The protein core includes basement membrane components, such as laminin, nidogen, and fibronectin, and components of the elastic fiber system, such as fibrillin-1, elastin, and latent transforming growth factor binding proteins, as well as enzymatically active components, such as metalloproteinases, the extracellular chaperone clusterin, and the cross-linking enzyme lysyl oxidase-like 1 (LOXL1). Ultrastructural evidence suggests that XFM is multifocally produced by intraocular cells, such as ciliary epithelial cells, preequatorial epithelial cells of the lens, trabecular and corneal endothelial cells, all cell types of the iris, as well as by extraocular cells, such as fibrocytes, vascular cells, and muscle cells. All cells involved in the exfoliation syndrome process disclosed common ultrastructural signs of active fibrillogenesis and metabolic activation, such as increased vesicular transport to the cell surface, XFM formation within infoldings of cellular surfaces, and a prominent rough endoplasmic reticulum. Finally, cells involved in the production of XFM displayed a gene expression pattern characterized by the upregulation of elastic components, the transient upregulation of LOXL1, and the dysregulated expression of cytoprotective gene products, matrix metalloproteinases, and their inhibitors, possibly leading to the accumulation and stable deposition of XFM.