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

假性剥脱性青光眼患者小梁网细胞和晶状体或虹膜上皮细胞氧化应激的评价

基本信息

批准号：
21592240
负责人：
MORI Kazuhiko
金额：
$ 2.91万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

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genome-wide association study data suggest that other genes but LOXL1 also relates to the pseudoexfoloation glaucoma(unpublished data), we concluded to re-evaluate the oxidative stress not only to the LOXL1 but also our new genetic loci after the genetic analysis has done.

假性剥脱性青光眼是难治性青光眼之一，由于眼压波动大，药物治疗效果不佳。有一种假说认为，包括氧化应激和TGF-β在内的细胞应激与假性剥脱物质的形成有关。以前，我们已经证明，在假性剥脱性青光眼患者中，房水中的TGF-β 3浓度也增加。本研究的目的不仅是评估氧化应激沿着TGF-β对假性剥脱物质形成的作用，而且还阐明与LOX-L1基因的关系。根据2009年和2010年的实验数据，我们可以评估假性剥脱性青光眼患者手术样本的标本和培养条件，如小梁网、透镜囊、虹膜和结膜。由于常规用于外科手术的丝裂霉素C，小梁网细胞难以培养，并且由于细胞纯化，虹膜色素上皮细胞不能作为单一细胞类型培养。因此，我们决定利用结膜下成纤维细胞作为我们的实验系统，该成纤维细胞易于生长并且被建议产生假性剥脱物质。2011年，我们利用结膜下成纤维细胞培养系统，证实了在不同时间和浓度的TGF-β 1、2和3诱导后，不仅LOXL 1和L0 XLin-1基因的mRNA表达水平增加，而且对过氧化氢的氧化应激负荷的响应。由于我们新的全基因组关联研究数据表明，除LOXL 1以外的其他基因也与假性脱嵌性青光眼有关（未发表的数据），因此我们得出结论，不仅要重新评估LOXL 1的氧化应激，还要在遗传分析完成后重新评估我们新的遗传基因座。