Apoptotic, oxidative stress, and endothelial signaling protein expression in lens epithelial cells of patients with pseudoexfoliation syndrome

Purpose Pseudoexfoliation syndrome (PXS) is associated with increased lens epithelial cell apoptosis; however, the underlying molecular mechanisms at the protein level remain unclear. This study aimed to investigate apoptotic, nitric oxide, and endothelial signaling-related protein expression (Caspase-3, −8, −9, eNOS, and VEGF-B) in anterior lens capsule epithelial cells of PXS patients and age-matched controls. Methods In this prospective comparative study, anterior lens capsule specimens were obtained from 55 patients with PXS and 30 age-matched cataract controls during phacoemulsification surgery. PXS severity was graded (Grades 1–3) based on slit-lamp biomicroscopic findings. Caspase-3, Caspase-8, Caspase-9, eNOS, and VEGF-B protein levels were measured by ELISA. Marker levels were compared between PXS and control groups and further analyzed according to disease grade (Grades 1–3) within the PXS group. Results No significant differences were observed between groups in age, gender distribution, cataract type, visual acuity, or intraocular pressure. Caspase-3, Caspase-9, VEGF-B, and eNOS levels were significantly higher in the PXS group compared to controls ( P < 0.001). Caspase-8 levels did not differ significantly between groups ( P = 0.711). In grade-based analysis, Caspase-3, Caspase-8, Caspase-9, and VEGF-B levels increased progressively from Grade 1 to Grade 3 (all P ≤ 0.003). In contrast, eNOS showed a decreasing profile across grades, with a significant reduction in Grade 3 versus Grade 1 ( P = 0.01). Conclusion PXS is associated with significant alterations in apoptosis-related, nitric oxide-related, and endothelial signaling proteins in lens epithelial cells, with a distinct grade-dependent molecular pattern. These findings identify Caspase-3, Caspase-9, VEGF-B, and eNOS as potential severity-associated biomarkers and therapeutic targets in PXS pathogenesis.