Loss of DNA-PK complex in recurrent pterygium suggests a role for defective double-strand break repair

Purpose Pterygium is a common ocular surface disorder strongly associated with ultraviolet (UV) radiation exposure and oxidative stress. Double-strand breaks (DSBs) are among the most deleterious forms of DNA damage, and their repair mainly relies on the non-homologous end joining (NHEJ) pathway, in which the DNA-dependent protein kinase (DNA-PK) complex plays a central role. This study investigated the expression of the DNA-PK complex components—DNA-PKcs, Ku70, and Ku86—in pterygium compared with healthy conjunctiva. Methods Conjunctival tissues were obtained from six patients undergoing surgical excision of recurrent pterygium and 6 age- and sex-matched controls undergoing ocular surgery without surface disease. Protein and transcript expression of DNA-PKcs, Ku70, and Ku86 were assessed by immunofluorescence, Western blotting, and real-time PCR. Results Immunofluorescence revealed markedly reduced DNA-PKcs immunoreactivity in the epithelium of pterygium conjunctiva compared with marked staining in controls. Western blot analysis demonstrated a significant decrease of DNA-PKcs protein, paralleled by a ~ 13-fold reduction of its mRNA. Similarly, Ku70 and Ku86 protein levels were dramatically reduced (by ~ 93.5% and ~ 92.0%, respectively) in pterygium compared with controls. Conclusions This study provides the first evidence of profound down-regulation of the DNA-PK complex in pterygium. The loss of DNA-PKcs and its regulatory subunits Ku70 and Ku86 suggests impaired DSB repair capacity, potentially driven by chronic UV-induced oxidative stress. These alterations may contribute to pterygium pathogenesis and recurrence, highlighting DNA-PK complex proteins as potential biomarkers of disease susceptibility and progression.