Abstract - Mucin polymers in the tear film protect the corneal surface from pathogens and modulate the tear-film flow characteristics. Recent studies have suggested a relationship between the loss of membrane-associated mucins and premature rupture of the tear film in various eye diseases. This work aims to elucidate the hydrodynamic mechanisms by which loss of membrane-associated mucins causes premature tear-film rupture. We model the bulk of the tear film as a Newtonian fluid in a two-dimensional periodic domain, and the lipid layer at the air-tear interface as insoluble surfactants. Gradual loss of membrane-associated mucins produces growing areas of exposed cornea in direct contact with the tear fluid. We represent the hydrodynamic consequences of this morphological change through two mechanisms: an increased van der Waals attraction due to loss of wettability on the exposed area, and a change of boundary condition from an effective negative slip on the mucin-covered areas to the no-slip condition on exposed cornea. Finite-element computations, with an arbitrary Lagrangian-Eulerian scheme to handle the moving interface, demonstrate a strong effect of the elevated van der Waals attraction on precipitating tear-film breakup. The change in boundary condition on the cornea has a relatively minor role. Using realistic parameters, our heterogeneous mucin model is able to predict quantitatively the shortening of tear-film breakup time observed in diseased eyes.