Intracapsular metformin bioactivity and its role in posterior capsule opacification

Posterior capsule opacification (PCO) is the most frequent long-term complication after cataract surgery, caused by proliferation of residual lens epithelial cells (LECs). Metformin, a common antidiabetic drug with antifibrotic properties, may act as a pharmacological modulator of this process. The purpose was to assess whether systemically administered metformin reaches the human lens capsule and inhibits LEC proliferation at physiologically relevant concentrations.

Metformin concentrations were quantified in serum and lens capsule tissue of patients with type 2 diabetes mellitus undergoing cataract surgery using high performance liquid chromatography-tandem mass spectrometry. Patients were stratified into low-dose (≤1000 mg/day) and high-dose (>1000 mg/day) groups. Additionally, anterior lens capsules from non-diabetic donors were cultured with or without metformin (0.75 pg/µL), and LEC proliferation was monitored for 14 days by live-cell imaging.

Metformin was detectable in both serum and capsule specimens, with a significant correlation between compartments (r=0.553, p=0.011). Capsule concentrations were similar across dose groups, while serum levels were higher in the low-dose group. In vitro, metformin significantly reduced LEC proliferation compared with controls (p<0.001).

Systemically administered metformin reaches the human lens capsule in vivo and suppresses LEC proliferation in vitro at clinically relevant concentrations. These findings provide first clinical and experimental evidence supporting metformin as a potential pharmacological adjunct to current strategies for PCO prevention.