Abstract
Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.
Highlights
Glaucoma, which is a leading cause of irreversible blindness worldwide [1,2], is a multifactorial disease characterized by retinal ganglion cell death [3]
The intraocular pressure (IOP) was significantly higher in the exfoliation glaucoma (EXG) group (26.4 ± 14.8) than in the control (14.3 ± 3.4; p = 0.0012) and primary open-angle glaucoma (POAG) (17.1 ± 14.8; p = 0.0142) groups; The IOP did not differ between the control and POAG groups (p = 0.1042)
The number of antiglaucoma medications did not differ between the POAG (2.0 ± 1.5) and EXG (2.9 ± 1.9) groups (p = 0.1884)
Summary
Glaucoma, which is a leading cause of irreversible blindness worldwide [1,2], is a multifactorial disease characterized by retinal ganglion cell death [3]. The trabecular dysfunction can obstruct the outflow of the aqueous humor (AH) [17,18], leading to IOP elevation and contributing to retinal ganglion cell death [21]. Antioxidants can scavenge reactive oxygen and nitrogen species by interacting with various redox signaling pathways [22], which prevents retinal ganglion cell death [23]. Oral supplementation of antioxidants might decrease IOP in patients with glaucoma [28]. Overall, this evidence suggested that oxidative stress is likely to play a significant role in the pathogenesis of glaucoma; the clinical impact of oxidative stress on the pathogenesis of glaucoma and the relationship between systemic redox status and intraocular ocular oxidative stress in various types of glaucoma are still to be investigated
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