Towards a closed eye model of the pre-ocular tear layer

Although the tear film has been extensively studied as it exists in the ope n eye state, until recently very little was known as to what happens to the tear film on eye closure. Recent studies have shown that eye closure resul ts in a profound change in the composition, origins, turnover and physiolog ical functions of the tear film. These changes include a shift from an indu cible, neurologically controlled, lacrimal secretion containing among other proteins primarily lysozyme, lactoferrin and tear specific lipocalin, to a much slower, constitutive-type of secretion, composed almost exclusively o f sIgA. This change is accompanied by the build-up of sialoglycoproteins of epithelial and goblet cell origin, the build-up and activation of compleme nt and the build-up of serum proteins. In addition, various cytokines and p roinflammatory mediators accumulate. including some which are potent induce rs of angiogenesis and leukochemotaxis. The closed eye also exhibits the re cruitment and activation of massive numbers of PMN cells. This results in a stagnant, closed eye layer, which is extremely rich in reactive complement products. PMN cell proteases including protease-3, elastase. capthepsin G, MMP-9 and urokinase. We have postulated that this shift represents a funda mental change in host-defense strategies from a passive-barrier defense to an active immune, inflammatory, phagocyte-mediated process and that this sh ift is necessitated in order to protect the cornea from entrapped microorga nisms. Studies have shown that autologous cell damage is avoided in closed eye tea r fluid. by the accumulation of several modulators of complement activation . which shift activation towards opsonization of entrapped microorganisms a nd the build-up of a wide array of antiproteases. Some of the latter are li kely to arise from the ocular surface tissues. Corneal neat neovasculation may be avoided in part by the build-up of alpha 2-macroglobulin and the con version of plasminogen to angiostatin. It is highly probable that other bio active protein fragments are produced in the closed eye, which contribute t o homeostasis. Areas of future study are indicated. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.