Molecular pathology of pseudoexfoliation syndrome/glaucoma – New insights from LOXL1 gene associations

Pseudoexfoliation (PEX) syndrome is a generalized disease of the extracellular matrix and a major cause of severe open-angle glaucoma. Single nucleotide polymorphisms (SNPs) in exon 1 of the lysyl oxidase-like 1 (LOXL1) gene have been recently identified as strong genetic risk factors for both PEX syndrome and PEX glaucoma. LOXL1 is a pivotal cross-linking enzyme in extracellular matrix metabolism and seems to be specifically required for elastic fiber formation and stabilization. This review outlines our current understanding of the role of LOXL1 in the pathophysiology of PEX syndrome and PEX glaucoma. The available data suggest that LOXL1 is differentially regulated dependent on the phase of progression of the fibrotic process. While increased levels of LOXL1 participate in the formation of abnormal PEX fiber aggregates in the initial phase of fibrogenesis, inadequate tissue levels may promote elastotic processes in advanced stages of the disease. Although the functional significance of LOXL1 in the specific PEX-associated matrix process still has to be determined, elucidation of the underlying molecular pathogenesis has been evolving, and might eventually open new approaches for specific treatment strategies in the future.