Among the observed molecular species of LPA, LPA16:0 and LPA18:1 were the dominant ones in a-SOAG (
Figs. 3B,
3C,
3G), and their levels generally agreed with those of LPC species. ATX shows a preference for saturated LPC substrates with long acyl chains (18:0 << 16:0 and 18:0 << 18:1),
43,44 (indicating that these LPA species are probably produced within the AH and are not extravasated from plasma). This result is in good agreement with the results of AUC analysis and multiple linear regression analysis (
Tables 31552–
5). Although ATX, total LPA, and total LPC all showed high diagnostic performance in their ability to discriminate between control and glaucoma patients, ATX had higher diagnostic performance than LPA or LPC in controls versus a-POAG (NTG and POAG) and controls versus a-SOAG (SOAG and XFG) (
Table 5). However, total LPA showed a larger AUC in a-POAG than in a-SOAG, and we believe that this is in part explained by the dominance of ATX-preferred species of LPA in POAG. In addition, multiple linear regression analysis in glaucoma subjects revealed that ATX was a significant predictor for IOP (
Table 4). Compared with previous studies, there was a relatively high value of lipids in the aqueous humor. We speculate that it is due, in part, to the difference of the methods of presentation. For example, Edwards et al. previously investigated phosphatidylcholine spectrum for aqueous humor samples from a control and from a POAG donor,
20 and they reported the phosphatidylcholine value by picomolar (pM) for each species (i.e., 18:0/18:0 PC, 18:2/22:6 PC) with normalization by the total average protein in the aqueous humor (pmol per species/μg protein). In the present study, we have shown the LPC as a total LPC, which is the sum of each LPC species (i.e., 16:0+16:1+18:0+18:2 LPC); therefore, the total was summed into the nanomolar range. In the earlier study, it was reported that there were no significant differences between normal and POAG eyes
20; this is in good accordance with our present result as there are no significant differences of LPC values between control and OAG eyes with lower IOP (data not shown). The present study is the first to investigate the quantification of lysophospholipids in glaucoma subjects, especially for LPA, and including SOAG and XFG patients, the glaucoma subtypes with suspected disruption of the blood–aqueous barrier. These data collectively suggest that the high value of LPA is related to the upregulation of ATX and the LPA produced by ATX may have a prominent role in the pathogenesis of IOP elevation in POAG and SOAG. Moreover, we recently reported that there was significant ATX expression in conventional outflow pathway specimens from glaucoma patients, and ATX expression was upregulated by dexamethasone (Dex) treatment in human TM cells.
45 In the study, we demonstrated that the fibrotic response in TM cells was induced by Dex, possibly by the de novo production of LPA by ATX in the aqueous humor or outflow tissues.