Megumi Honjo1, Nozomi Igarashi1, Makoto Kurano2,3, Yutaka Yatomi2,3,4, Koji Igarashi5, Kuniyuki Kano3,6, Junken Aoki3,6, Robert N Weinreb7, Makoto Aihara1. 1. Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 2. Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 3. CREST, Japan Science and Technology Corporation (JST), Saitama, Japan. 4. Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan. 5. Bioscience Division, Reagent Development Department, AIA Research Group, TOSOH Corporation, Kanagawa, Japan. 6. Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan. 7. Hamilton Glaucoma Center, Shiley Eye Institute and Department of Ophthalmology, University of California-San Diego, La Jolla, California, United States.
Abstract
Purpose: To compare the levels of autotaxin (ATX), lysophosphatidic acid (LPA), and lysophosphatidylcholine (LPC) in the aqueous humor (AH) of healthy control subjects with those of patients with different subtypes of glaucoma, and also to investigate the relationship of the ATX-LPA pathway with IOP and subtype of glaucoma. Methods: This study included 164 eyes of 164 consecutive cases of cataract and glaucoma surgery (37 healthy, 31 normal tension glaucoma, 49 primary open angle glaucoma, 28 secondary open angle glaucoma, and 19 exfoliation glaucoma). Aqueous levels of LPA, LPC, and ATX were quantified using liquid chromatography-tandem mass spectrometry and a two-site immunoenzymetric assay. The association between aqueous levels of ATX/LPA/LPC and IOP elevation in different glaucoma subtypes was investigated. The diagnostic values of indices of the ATX-LPA pathway were compared using receiver operating characteristic curve analysis. Results: Notable increases in ATX/LPA/LPC levels in glaucoma patients were observed. The ATX-LPA pathway was significantly related to IOP elevation and the subtype of glaucoma, especially in SOAG and XFG patients, and the area under the curve was significant for discriminating glaucoma eyes from healthy eyes. Conclusions: Bioactive ATX/LPA/LPC concentrations were present in aqueous humor, and higher ATX and LPA concentrations were significantly correlated with IOP in all study subjects. Furthermore, the ATX-LPA pathway was significantly related to glaucoma subtype. These results reveal the potentially important role of the ATX-LPA pathway for IOP regulation in healthy subjects and glaucoma patients.
Purpose: To compare the levels of autotaxin (ATX), lysophosphatidic acid (LPA), and lysophosphatidylcholine (LPC) in the aqueous humor (AH) of healthy control subjects with those of patients with different subtypes of glaucoma, and also to investigate the relationship of the ATX-LPA pathway with IOP and subtype of glaucoma. Methods: This study included 164 eyes of 164 consecutive cases of cataract and glaucoma surgery (37 healthy, 31 normal tension glaucoma, 49 primary open angle glaucoma, 28 secondary open angle glaucoma, and 19 exfoliation glaucoma). Aqueous levels of LPA, LPC, and ATX were quantified using liquid chromatography-tandem mass spectrometry and a two-site immunoenzymetric assay. The association between aqueous levels of ATX/LPA/LPC and IOP elevation in different glaucoma subtypes was investigated. The diagnostic values of indices of the ATX-LPA pathway were compared using receiver operating characteristic curve analysis. Results: Notable increases in ATX/LPA/LPC levels in glaucomapatients were observed. The ATX-LPA pathway was significantly related to IOP elevation and the subtype of glaucoma, especially in SOAG and XFG patients, and the area under the curve was significant for discriminating glaucoma eyes from healthy eyes. Conclusions: Bioactive ATX/LPA/LPC concentrations were present in aqueous humor, and higher ATX and LPA concentrations were significantly correlated with IOP in all study subjects. Furthermore, the ATX-LPA pathway was significantly related to glaucoma subtype. These results reveal the potentially important role of the ATX-LPA pathway for IOP regulation in healthy subjects and glaucomapatients.