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Abstract #21931 Published in IGR 10-4
The management of exfoliative glaucoma
Ritch RProgress in Brain Research 2008; 173: 211-224
Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. XFS plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. It is accompanied by an increase in serious complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss. It is associated systemically with an increasing number of vascular disorders, hearing loss, and Alzheimer's disease. XFS appears to be a disease of elastic tissue microfibrils. The characteristic fibrils, composed of microfibrillar subunits surrounded by an amorphous matrix comprising various glycoconjugates, contain predominantly epitopes of elastic fibers, such as elastin, tropoelastin, amyloid P, vitronectin, and components of elastic microfibrils, such as fibrillin-1, fibulin-2, vitronectin, microfibril-associated glycoprotein (MAGP-1), and latent TGF-β binding proteins (LTBP-1 and LTBP-2), the proteoglycans syndecan and versican, the extracellular chaperone clusterin, the cross-linking enzyme lysyl oxidase, and other proteins. A recent milestone study showed that two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodeling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protein disorder.
Dr. R. Ritch, New York Eye and Ear Infirmary, New York, NY 10003, USA. ritchmd@earthlink.net
