Immunohistochemical Expression of Pro-Inflammatory Cytokines, Transforming Growth Factors and Tumor Necrosis Factor-a in Pseudoexfoliation Syndrome: A Comparative Study with Non-PEX Cataract Controls

Purpose: The purpose of the present study is to investigate the immunohistochemical expression patterns of interleukins (IL-1, IL-6, IL-8), transforming growth factors (TGF-β1, TGF-β2), and tumor necrosis factor-alpha (TNF-α) in the anterior lens capsule of patients with pseudoexfoliation syndrome (PEX) compared age-matched non-PEX cataract controls. Materials and Methods: A comparative immunohistochemical analysis was performed on anterior lens capsule specimens obtained from patients diagnosed with PEX and from age-matched patients without clinical evidence of PEX undergoing cataract surgery. A total of 79 participants were enrolled in the study, consisting of 40 patients in the PEX group and 39 patients in the CONTROL group. The mean age was 80.9 years (range: 69–91 years) for the PEX group and 79.8 years (range: 66–90 years) for the CONTROL group. Semi-quantitative assessment of staining intensity was performed separately in lens epithelial cells and the basement membrane; the previously used term “stromal tissue” was removed because the anterior lens capsule does not contain a true stromal compartment. Staining intensity was graded as negative (0), weak (+), moderate (++), or strong (+++). Between-group differences were analyzed using the two-sided Mann–Whitney U test because the staining scores were ordinal. Exact two-sided p-values, Holm-adjusted p-values, and effect sizes (r) were calculated. The study adhered to the tenets of the Declaration of Helsinki and The Ethical Committee of the Aristotle University of Thessaloniki approved the study (Number of approval: 6.703/14.06.2022). Results: Significant differences between PEX and control specimens were identified in epithelial staining for all six investigated markers. IL-6, IL-8, TGF-β1, TGF-β2, and TNF-α showed higher epithelial staining in PEX specimens, whereas IL-1 showed significantly lower epithelial staining. In the basement membrane, significant differences were observed for IL-1, IL-8, and TGF-β2, whereas no significant differences were observed for TGF-β1, TNF-α, or IL-6. Conclusions: The findings demonstrate distinct immunohistochemical expression patterns of inflammatory and profibrotic mediators in the anterior lens capsule in PEX. The observed associations support involvement of altered inflammatory and extracellular-matrix-related signaling but do not establish cellular origin or causality. In particular, the findings cannot establish that lens epithelial cells are the principal source of the investigated mediators or that any individual mediator directly promotes pseudoexfoliative material deposition.