Potentially compromised systemic and local lactate metabolic balance in glaucoma, which could increase retinal glucose and glutamate concentrations

Abstract

To investigate the association between lactate metabolism and glaucoma, we conducted a multi-institutional cross-sectional clinical study and a retinal metabolomic analysis of mice with elevated intraocular pressure (IOP) induced by intracameral microbead injection. We compared lactate concentrations in serum and aqueous humor in age-matched 64 patients each with primary open-angle glaucoma (POAG) and cataract. Neither serum nor aqueous humor lactate concentrations differed between the two groups. Multiple regression analysis revealed that only body mass index showed a significant positive correlation with serum and aqueous humor lactate concentration in POAG patients (r_s = 0.376, P = 0.002, and r_s = 0.333, P = 0.007, respectively), but not in cataract patients. L-Lactic acid was one of the most abundantly detected metabolites in mouse retinas with gas chromatography and mass spectrometry, but there were no significant differences among control, 2-week, and 4-week IOP elevation groups. After 4 weeks of elevated IOP, D-glucose and L-glutamic acid ranked as the top two for a change in raised concentration, roughly sevenfold and threefold, respectively (ANOVA, P = 0.004; Tukey-Kramer, P < 0.05). Glaucoma may disrupt the systemic and intraocular lactate metabolic homeostasis, with a compensatory rise in glucose and glutamate in the retina.