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Editors Selection IGR 16-4
Clinical Forms of Glaucoma: LOXL1 expression in lens capsule in XFS/G
Comment by Robert Ritch & Syril Dorairaj on:
27458 LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma, Khan TT; Li G; Navarro ID et al., Molecular Vision, 2010; 16: 2236-2241
The stated objectives of this prospective, cross-sectional study by Khan et al. (1819) were 1) to study and quantify lysyl oxidase-like 1 (LOXL1) expression in freshly collected lens capsules from exfoliation syndrome (XFS), exfoliation glaucoma (XFG), and normal cataract controls; and 2) to investigate the effects of four glaucoma medications on LOXL1 expression in primary human lens epithelial cell cultures to see if they could affect LOXL1 expression. The authors found reduced LOXL1 expression in XFG but not XFS. The drug treatment incubation studies suggested that the change in LOXL1 expression observed in XFG is not attributable to glaucoma therapy. If a causative functional relationship can be validated, modification of LOXL1 expression in affected tissues may present a novel treatment strategy for this disorder. For better validation, the authors could take their analysis a step further and investigate other exfoliation material-producing anterior segment tissues.
Interestingly, the authors' first conclusion is in line with previous reports showing that LOXL1 mRNA expression might be significantly upregulated in early stages of XFS and downregulated in advanced stages with or without glaucoma. Inadequate activity could adversely affect elastin homeostasis and biomechanical properties of the extracellular matrix, and hence predispose to matrix disorganization, alteration, or dysfunction. Elastotic alterations have been described in various tissues, such as lamina cribrosa, conjunctiva, skin, and vessel walls, of patients with advanced XFS/XFG, suggesting abnormal regulation of elastin biosynthesis.
The second conclusion could have practical therapeutic implications. Drugs which affect LOXL1 expression and function might modulate production and accumulation of exfoliation material. One goal of future therapy would be to counteract mechanisms that modify LOXL1 expression in affected tissues. It would have been interesting had the authors evaluated the expression potential of these antiglaucoma drugs on trabecular meshwork as well.
Many patients with XFS never develop glaucoma. Modifier genes presumably play a determining role, modulating the activity of LOL1 affected by the involved SNPs. Environmental conditions associated with fibrotic processes, such as oxidative stress and hypoxia, may regulate both LOXL1 expression and activity. Gene-environment interactions may further regulate production and deposition of exfoliation material. Understanding the epigenetics of XFS/XFG and applying these new therapeutic concepts might eventually open novel approaches for specific treatment strategies.
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