Elevated carbonic anhydrase-1 in the aqueous humor in diabetic macular edema: associations between inflammatory cytokines and retinal vascular dysfunction

Purpose This study aimed to investigate the expression of carbonic anhydrase-1 (CA-1) in the aqueous humor of patients with diabetic macular edema (DME) and to explore its correlations with other cytokines and macular structure in a real-world setting. Methods This was a retrospective cross-sectional study. A total of 74 patients were enrolled in the DME group, and 30 patients were included in the control group. Aqueous samples were collected before intravitreal injections or relevant surgical procedures. The concentrations of CA-1, prekallikrein (PK), intercellular adhesion molecule-1 (ICAM-1), vascular intercellular adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and interleukin-8 (IL-8) were measured using a cytometric bead array (CBA). Retinal structural biomarkers were examined using optical coherence tomography (OCT) and fundus photography. Results The levels of CA-1 in the aqueous humor were markedly elevated in patients with DME compared to the control group. The DME group showed a significantly higher geometric mean CA-1 level than the control group (geometric mean ratio = 10.65, 95% CI: 3.64–31.14, p < 0.001). Receiver-operating characteristic curve analyses (AUC = 0.89; 95% CI: 0.871–0.981, p < 0.001) revealed that CA-1 has a strong discriminatory ability for distinguishing DME patients. In addition, other cytokines (PK, ICAM-1, VCAM-1, and IL-8) in the aqueous humor were elevated in the DME group compared to the control group ( p < 0.05). In the DME group, CA-1 levels exhibited positive correlations with PK, ICAM-1, VCAM-1, MCP-1, VEGF, IL-6, and IL-8 ( r = 0.306, 0.551, 0.347, 0.589, 0.349, 0.248, and 0.538, respectively; all p < 0.05). Conversely, CA-1 levels showed a negative correlation with retinal hemorrhage ( r = −0.330, p = 0.016) and did not show significant association with other macular structural parameters. Conclusion In DME patients, CA-1 levels were significantly elevated and showed associations with PK, ICAM-1, VCAM-1, VEGF, MCP-1, IL-6, and IL-8. These findings suggest that higher CA-1 levels are associated with increased retinal vascular permeability and inflammation in patients with DME. Clinical trial registration https://www.chictr.org.cn/index.html , identifier 268319.