ABSTRACT: Keratoconus (KC) is characterized by corneal thinning due to pathologic degradation of corneal stromal collagen. This study investigates the role of β-estradiol in corneal collagen degradation using both tear fluid samples from KC and non-KC patients and in vitro models (co-culture and 3D collagen hydrogel model). In tear fluids, we observed sex-specific differences in matrix metalloproteinase (MMP) activity, secretory phospholipase A2 (PLA2G2A) levels, and in cytokine profiles, including interleukin (IL-) 2, 3, 5, 6, 8, 11, 13, 15, 19, 24, 27, 31, and 32 tumor necrosis factor (TNF-α), angiopoietin 2, vitamin D binding protein, insulin growth factor binding proteins (IGFBP3), vascular endothelial growth factor (VEGF), and receptor for advanced glycation end product (RAGE). Our model
