Glucose Metabolic Characterization of Human Aqueous Humor in Relation to Wet Age-Related Macular Degeneration

Purpose: Energy compromise underpins wet age-related macular degeneration (wAMD) pathogenesis, but the relationship between glucose metabolism and the disease remains unclear. Here, we characterized aqueous humor (AH) to elucidate glucose-related metabolic signatures in patients with wAMD. Methods: In total, 25 eyes of 25 patients with wAMD were divided into phakic (15 eyes), pseudophakic (10 eyes), and intravitreal injections of ranibizumab (13 eyes) wAMD groups. Twenty patients with cataract (21 eyes) served as controls. Ultrahigh-performance liquid chromatography tandem mass spectrometry was used to quantitatively characterize AH. Results: Twenty-one metabolites related to glucose metabolism were identified in AH from 45 patients. Tricarboxylic acid (TCA)-related metabolic substrates, including citrate, were detected in AH and were significantly increased in AMD (P < 0.01) and AMD pseudophakic groups (P < 0.05). In contrast, α-ketoglutarate levels were decreased in the AMD group (P < 0.05). The α-ketoglutarate/citrate ratio was significantly decreased, corresponding to 71.71% and 93.6% decreases in the AMD (phakic and pseudophakic) groups as compared with controls (P < 0.001), revealing a significant positive correlation with glutamine. A lower mean glutamine and higher glutamate level were detected in AMD cases compared with controls. No significant differences were observed for lactic acid or other Krebs cycle metabolites. Intravitreal injection significantly alleviated mean central foveal thickness but did not significantly alter metabolites. Conclusions: Compromised glucose TCA cycle and altered glutamine metabolism are implicated in the AH metabolism in wAMD. These findings highlight potential treatments for alleviating wAMD from a metabolic perspective.