Biological functions of tear film

Abstract

Tears have a vital function to protect and lubricate the ocular surface. Tear production, distribution and clearance is tightly regulated by the lacrimal functional unit (LFU) to meet ocular surface demands. The tear film consists of an aqueous-mucin layer, containing fluid and soluble factors produced by the lacrimal glands and mucin secreted by the goblet cells, that is covered by a lipid layer. The array of proteins, glycoproteins and lipids in tears function to maintain a stable, well-lubricated and smooth optical surface. Tear factors also promote wound healing, suppress inflammation, scavenge free radicals, and defend against microbial infection. Disease and dysfunction of the LFU leads to tear instability, increased evaporation, inflammation, and blurred and fluctuating vision. The function of tear components and the consequences of tear deficiency on the ocular surface are reviewed.

Keywords: Dry eye; Dry eye disease; Growth factor; Innate immunity; Lipid; Mucin; Pain; Tear stability; Tears; Visual acuity.

Figure 1.

Tear film structure. Evidence suggests the tear film consists of membrane associated mucins (MAM) such as MUC16 that form the glycocalyx on the apical epithelium, a secretory mucus layer containing soluble MUC5AC mucin secreted by the conjunctival goblet cells, aqueous fluid and electrolytes, and proteins secreted by the lacrimal glands. The surface of the tears is covered with a lipid layer with polar lipids adjacent to the aqueous layer and nonpolar lipids interfacing with the air.

Figure 2.

Lacrimal Functional Unit (LFU). The LFU regulates the production, delivery and clearance of tears to maintain a homeostatic environment on the ocular surface. Anatomically, the LFU includes the main and accessory lacrimal glands, Meibomian glands, conjunctival goblet cells, the surface epithelium, eye lids, lacrimal drainage system, the glandular and mucosal immune system and the interconnecting innervation. The neural component of the LFU consists of a reflexive loop starting at the highly innervated cornea surface with afferent traffic to the central nervous system, including the brainstem and cerebral cortex. These afferents project to secretory and motor efferent nerves to drive tear production and blinking. The efferent pathways are found to terminate within the secretory glands. Innate and adaptive inflammatory/immune pathways maintain immune tone to defend the ocular surface from microbial infection. Dysfunction of the LFU stimulates cytokine, chemokine and protease production by ocular surface epithelial and immune cells (cytokine storm) that results in autoantigen release, antigen presenting cell activation and migration to the lymph nodes and priming of effector CD4+ T cells that can traffic to the ocular surface and can provide the cytokines to stimulate autoantibody production by plasma cells. These immune mediators and cells cause ocular surface epithelial disease and can sensitize pain receptors.