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13 Pathogenesis: Emphasis on Dry Eye and the Role of the Lacrimal Functional Unit . . .

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humidity, wind, UV irradiation, allergens, and irritants, such as pollutants and particulate matter. The tear Þlm must have sufÞcient stability to buffer the ocular surface microenvironment against these challenges. Protective components of the tear Þlm, such as immunoglobulin A, lactoferrin, lysozyme, and peroxidase, resist bacterial or viral infections. The surface lipid layer minimizes evaporation of the aqueous component of the tear Þlm in adverse environments. Additionally, tear production may be stimulated to help wash out particulates, irritants, and allergens.

Fourth, the tear Þlm provides a trophic environment for the corneal epithelium. Because it lacks vasculature, the corneal epithelium depends on the tear Þlm for growth factors and for certain nutritional support. The electrolyte and oxygen supply of the corneal epithelium is provided by the tear Þlm. While most of the glucose utilized by the corneal epithelium is supplied by diffusion from the aqueous humor, tears contain about 25 μg/mL glucose, roughly 4% of the glucose concentration in blood [38], a sufÞcient concentration to support non-muscular tissue. Tear Þlm anti-oxidants help maintain a reducing environment and scavenge free radicals. The tear Þlm also contains a plethora of growth factors, important for the constant regeneration of the corneal epithelium and for wound healing.

tear Þlm viscosity and protects against the shear force of blinking that would otherwise cause irritation, inßammation, and accelerated sloughing of surface epithelial cells. The mucin layer also helps to maintain optical clarity and smoothness of the cornea [39].

At Þrst glance the mucin layer appears loosely organized and amorphous, although recent Þndings have demonstrated that it is highly organized in a manner that facilitates its function. The ocular surface epithelia express transmembrane mucins 1, 2, 4, and 16, which form the glycocalyx and anchor the mucin layer to the hydrophobic epithelial cell surface [40Ð43]. The membrane-spanning domain of MUC1 anchors it to epithelial cells, and its extracellular domain extends 200Ð500 nm into the glycocalyx [44]. MUC4, expressed by the stratiÞed conjunctival epithelium [45], forms a sialomucin complex on the surfaces of corneal and conjunctival epithelial cells and can also be shed into tear ßuid as a soluble mucin [46]. Conjunctival goblet cells secrete the soluble mucin MUC5AC [47], which interacts with the membrane-bound mucins and the aqueous layer to form a water-trapping gel. Lacrimal glands secrete MUC7 into the tear ßuid [48, 49]. MUC1 and MUC4 have been shown to prevent inßammatory cell adhesion [50, 51], suggesting that the mucin layer may function, in general, to prevent adherence to or repel inßammatory cells, bacteria, or debris from the ocular surface [43, 47]. In summary, the chemical interactions between membrane and soluble mucins

13.9The Makeup of the Tear Film create a stable tear Þlm that coats the ocular

The tear Þlm is currently viewed as a hydrated mucin gel that contains ßuid, electrolytes, and proteins that are secreted by the lacrimal glands and ocular surface epithelium. The surface is covered with a lipid layer that is produced by the meibomian glands.

13.9.1 Hydrated Mucin Gel

The mucin layer functions as a surfactant for the ocular surface, facilitating even spread of tears over the hydrophobic epithelium. It maintains

surface epithelium and facilitate tear Þlm spreading and ocular surface wetting. An intact and hydrated mucin gel helps protect the epithelium from environmental insult and minimizes shear forces during blinking [35, 39, 52].

13.9.2 Lipid Profile

The lipid layer, secreted by the meibomian glands whose ducts exit just anterior to the mucocutaneous junction of the lids, functions to facilitate tear Þlm spreading over the corneal surface and minimize tear evaporation [35, 39, 52, 53]. In

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