Evaluation of oxidative stress on trabecular meshwork cells and lens or iris epithelial cells in pseudoexfoliation glaucoma patients

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Pseudoexfoliation glaucoma is one of the intractable types of glaucoma, which resist to the medical treatment due to the large fluctuation of intraocular pressure. There is a hypothesis that the cellular stresses including oxidative stress and TGF-beta are related to the formation of pseudoexfoliation substances. Previously, we had demonstrated that TGF-beta3 concentration in the aqueous humor also increased in pseudoexfoliation glaucoma patients. The purpose of this study was not only to evaluate the role of the oxidative stress along with the TGF-beta to the formation of the pseudoexfoliation substances, but also to clarify the relationship to the LOX-L1 gene. From the experimental data through 2009 and 2010, we could evaluate the specimens and culture conditions from the surgical samples of pseudoexfoliation glaucoma patients, such as trabecular meshwork, lens capsule, iris, and conjunctivae. Trabecular meshwork cells had a difficulty to culture due to the mitomycin C which is routinely utilized for the surgical procedure, and iris pigmented epithelial cells could not be cultured as a single cell types because of the cell purification. Therefore, we decided to utilize the subconjunctival fibroblasts, which grow easily and are suggested to produce pseudoexfoliation substances, as our experimental system. In 2011, we confirmed not only the increase of the mRNA expression levels of LOXL1 and fibrillin-1 gene after the induction of TGF-beta 1, 2, and 3 with different duration and concentration, but also the response to the oxidative stress loading of the hydrogen peroxide, utilizing subconjuncival fibroblasts culture system. Since our new genome-wide association study data suggest that other genes but LOXL1 also relates to the pseudoexfoloation glaucoma(unpublished data), we concluded to re-evaluate the oxidative stress not only to the LOXL1 but also our new genetic loci after the genetic analysis has done.