The core aqueous stratum is secreted by the main and accessory lacrimal glands (see Chapter 1, Fig 1-38). The main lacrimal gland is divided into 2 anatomical parts, the orbital and the palpebral lobes, by the lateral horn of the levator aponeurosis. The glands of Krause, which constitute two-thirds of the accessory lacrimal glands, are located in the lateral part of the upper fornix. A number of Krause glands are also present in the lower fornix. The glands of Wolfring are variably located along the proximal margin of each tarsus. The accessory lacrimal glands are structurally like the main lacrimal gland.
The main lacrimal gland is richly innervated by parasympathetic nerves containing the neurotransmitters acetylcholine and VIP. The sympathetic innervation is less dense than the parasympathetic and contains norepinephrine and NPY as neurotransmitters. The sensory nerves are sparsely supplied with the neurotransmitters substance P and calcitonin gene–related peptide (CGRP). The accessory lacrimal glands are densely innervated, but the majority of nerves are unidentified. Some of this innervation consists of nerves containing VIP, substance P, and CGRP.
The aqueous stratum consists of electrolytes, water, and proteins. Electrolytes and small molecules regulate the osmotic flow of fluids between the corneal epithelial cells and the tear film, buffer tear pH, and serve as enzyme cofactors in controlling membrane permeability. The sodium (Na+) concentration of tears parallels that of serum; however, the concentration of potassium (K+) is 5–7 times that of serum. Na+, K+, and chloride (Cl–) regulate the osmotic flow of fluids from the cornea to the tear film and thereby contribute to corneal clarity. Bicarbonate () regulates tear pH. Other tear electrolytes (Fe2+, Cu2+, Mg2+, Ca2+, PO43–) are enzyme cofactors.
Tear film solutes include urea, glucose, lactate, citrate, ascorbate, and amino acids. All enter the mucoaqueous layer of the tear film via the systemic circulation, and their concentrations parallel those of serum levels. Fasting tear glucose levels are 3.6–4.1 mg/mL in those with and those without diabetes mellitus. However, after a 100-mg oral glucose load, tear glucose levels exceed 11 mg/mL in 96% of diabetic persons tested.
Proteins in the mucoaqueous layer of the tear film include immunoglobulin (Ig) A and secretory IgA (sIgA). IgA is formed by plasma cells in interstitial tissues of the main and accessory lacrimal glands (see Chapter 1, Fig 1-39) and by the substantia propria of the conjunctiva. The secretory component is produced within lacrimal gland acini, and sIgA is secreted into the lumen of the main and accessory lacrimal glands. IgA plays a role in local host-defense mechanisms of the external eye, as shown by increased levels of IgA and IgG in human tears associated with ocular inflammation. Other immunoglobulins in tears are IgM, IgD, and IgE.
Vernal conjunctivitis causes elevated tear and serum levels of IgE, increased IgE-producing plasma cells in the giant papillae of the superior tarsal conjunctiva, and elevated histamine levels. Increased levels of tear histamine support the concept of conjunctival TC (tryptase and chymotryptic proteinase containing) mast-cell degranulation triggered by IgE–antigen interaction. TC mast cells are unique to the conjunctiva and are specifically sensitive to commercially available topical mast-cell stabilizers.
Levels of matrix metalloproteinase 9 (MMP-9) in the tear film have been shown to be elevated in patients with severe disorders affecting the ocular surface, including Sjögren syndrome and graft-vs-host disease, as well as in patients after laser in situ keratomileusis (LASIK). MMP-9 cleaves epithelial basement membrane components and tight-junction proteins. MMP-9 levels have been shown to parallel corneal staining severity and may represent a sign of late-stage DES. In addition, expression of intercellular adhesion molecule 1 (ICAM-1) has been shown to be upregulated on lymphocytes and/or vascular endothelial cells, resulting in lymphocytic migration to the lacrimal and conjunctival tissues in DES.
Lysozyme, lactoferrin, group II phospholipase A2, lipocalins, and defensins are important antimicrobial constituents of the mucoaqueous layer. Interferon is also present; it inhibits viral replication and may be efficacious in limiting the severity of herpetic keratitis.
In addition, the mucoaqueous layer of the tear film contains a wide array of cytokines and growth factors, including transforming growth factor βs, epidermal growth factor, fibroblast growth factor β, interleukin 1α and 1β, and tumor necrosis factor α. These constituents may play a role in the proliferation, migration, and differentiation of corneal and conjunctival epithelial cells. They may also regulate wound healing of the ocular surface.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.