Biological functions of tear film

doi:10.1016/j.exer.2020.108115

Experimental Eye Research

Volume 197, August 2020, 108115

https://doi.org/10.1016/j.exer.2020.108115 Get rights and content

Highlights

•
The complex structure and composition of the tear film protects the cornea, promotes wound healing and maintains eye comfort and quality vision.
•
The integrated lacrimal functional unit regulates tear production and maintains stability.
•
Altered tear composition and stability in dry eye cause eye inflammation, corneal disease and blurred vision.

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.

Introduction

The tear film is the interface between the ocular surface epithelium and the environment. Although the precorneal tear thickness is estimated to be 3 μm (King-Smith et al., 2000), it has a highly complex composition containing water, electrolytes, mucins, and an array of proteins and lipids. Indeed, a study surveying human tear fluid using liquid chromatography-mass spectroscopy (LC-MS) reported detection of over 1500 proteins (Zhou et al., 2012). The structure of the tear film continues to evolve, but evidence suggests it consists of a hydrated mucus layer (secretory mucus layer) covered by lipid that moves over the glycocalyx on the surface epithelium (Fig. 1) (Yokoi and Georgiev, 2018). Knowledge regarding the biological function of the tears is based on activity of individual constituents (e.g. growth factors), imaging studies and the consequences of tear deficiency. Findings from these studies show tears function to maintain comfort, prevent infection, suppress inflammation, heal traumatic and surgical injuries, clear debris and maintain high quality vision. Evidence in support of these functions are reviewed herein.

Section snippets

Methods

A literature search of clinical and basic studies, and review articles published from 1960 to 2020 was performed in PubMed.gov using major terms tear film, tear function and tear stability and subheadings mucin, lipid, growth factors, cytokines, visual acuity and pain. The bibliographies of references identified by this strategy were also reviewed.

Regulation of tear production

The normal tear film contains a tightly controlled complement of ions, proteins and lipids which allow it to fulfill its basic functions. Perhaps its most important function is the primary optical surface of the eye (Tutt et al., 2000). The tear film assures eye comfort through its lubricative properties which decrease shear forces from the lid margin as it traverses the ocular surface during a blink cycle (Rolando and Zierhut, 2001). Reduced tear volume and altered tear film composition in DED

Stability

Maintenance of tear stability is essential for maintaining comfort and quality vision. Tear stability requires dynamic interaction between the major tear constituents described below. An unstable tear film is the hallmark of tear dysfunction/deficiency and maintenance of stability is a major goal of therapy.

Visual performance

The tear film is a critical component of the optical system of the eye. The tears and the anterior surface of the cornea account for approximately 80% of the refractive power for the eye (Rolando and Zierhut, 2001). Deterioration in cornea surface smoothness, reduced contrast sensitivity and increased optical aberrations that degrade retina image quality in eyes with tear film instability highlight the functional role of the tear film in maintaining high quality vision (Rieger, 1992). Studies

Trophic/wound healing factors

The aqueous-mucin tear layer contains numerous proteins, including growth and supportive factors. Some of these have a homeostatic function (e.g. suppress inflammation, maintain innervation or barrier), while others participate primarily in epithelial and/or stromal wound healing (Klenkler et al., 2007). Table 1 lists the most abundant tear growth factors and their function. Certain factors, such as epidermal growth factor (EGF), are secreted by the lacrimal gland into tears (Jones et al., 1997

Innate defense/antimicrobial factors

Since the initial discovery of lysozyme in the tears by Alexander Fleming in 1922, many anti-infective molecules have been found in the normal tear film (Gallo, 2013). They include lysozyme (present at 2.5 mg/ml) (Wiesner and Vilcinckas, 2010) and lactoferrin (present at 1.5 mg/ml) (Kijlstra et al., 1983; Wiesner and Vilcinskas, 2010). Lactoferrin's basic anti-bacterial mechanism is through its ability to bind free iron which is necessary for bacterial growth (Flanagan and Willcox, 2009). This

Anti-inflammatory/antioxidant factors

The tears contain factors that suppress inflammation, such as interleukin 1 receptor antagonist that binds the IL-1 receptor and inhibits IL-1 activity (Solomon et al., 2001), and TGF-β2 and vitamin A and its metabolites that suppress maturation and cytokine production by antigen presenting cells (Contreras-Ruiz and Masli, 2015; Lam et al., 2009; Pflugfelder et al., 2008; Ubels et al., 1986; Xiao et al., 2018) There are a number of antioxidants, including ascorbic acid, lactoferrin and

Summary

The tear film has a complex structure and composition that protects the cornea, promotes wound healing after injury and maintains eye comfort and high-quality vision. Altered tear composition and stability in DED causes eye irritation, corneal epithelial and nerve disease and blurred vision. The ease of collecting tear fluid, identification of relevant biomarkers in health and disease and more sensitive immunoassays that can be read by smartphones create technological opportunities for

Funding

This work was supported by NIH Grant EY11915 (SCP), NIH Core Grants-EY002520 & EY020799, Pathology Cell Core P30CA125123, Biology of Inflammation Center Baylor College of Medicine, an unrestricted grant from Research to Prevent Blindness, New York, NY (SCP), the Oshman Foundation, Houston, TX (SCP), the William Stamps Farish Fund, Houston, TX (SCP), Hamill Foundation, Houston, TX (SCP), Sid W. Richardson Foundation, Ft Worth, TX (SCP).

Declaration of competing interest

None of the authors have any financial or personal relationships to disclose that would cause a conflict of interest regarding this article.

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View full text

Biological functions of tear film

Highlights

Abstract

Introduction

Section snippets

Methods

Regulation of tear production

Stability

Visual performance

Trophic/wound healing factors

Innate defense/antimicrobial factors

Anti-inflammatory/antioxidant factors

Summary

Funding

Declaration of competing interest

Ocul. Surf.

Ocul. Surf.

Prog. Retin. Eye Res.

Biochim. Biophys. Acta

Exp. Eye Res.

Ocul. Surf.

J. Cataract Refract. Surg.

Biochimie

Exp. Eye Res.

Exp. Eye Res.

Prog. Retin. Eye Res.

Int. Rev. Cytol.

Exp. Eye Res.

Am. J. Ophthalmol.

Ocul. Surf.

Ophthalmology

Clin. Chim. Acta

Am. J. Ophthalmol.

Growth Hormone IGF Res.

Adv. Colloid Interface Sci.

Ophthalmology

Ophthalmology

Surv. Ophthalmol.

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome

Invest. Ophthalmol. Vis. Sci.

Dysfunctional tear syndrome: a Delphi approach to treatment recommendations

Cornea

A model for tear film thinning with osmolarity and fluorescein

Invest. Ophthalmol. Vis. Sci.

Human IgA inhibits adherence of Acanthamoeba polyphaga to epithelial cells and contact lenses

Can. J. Microbiol.

Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome

Invest. Ophthalmol. Vis. Sci.

Immunomodulatory cross-talk between conjunctival goblet cells and dendritic cells

PloS One

Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium

Invest. Ophthalmol. Vis. Sci.

Assessing the severity of keratitis sicca with videokeratoscopic indices

Ophthalmology

Tear cytokine and chemokine analysis and clinical correlations in evaporative-type dry eye disease

Mol. Vis.

Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores

Antimicrob. Agents Chemother.

Elevated levels of substance P in tears of patients with allergic conjunctivitis and vernal keratoconjunctivitis

Clin. Exp. Allergy

The birth of innate immunity

Exp. Dermatol.

Antimicrobial peptides as a major part of the innate immune defense at the ocular surface

Dev. Ophthalmol.

Contribution of mucins towards the physical properties of the tear film: a modern update

Int. J. Mol. Sci.

Cellular origin of mucins of the ocular surface tear film

Adv. Exp. Med. Biol.

Comparison of the transmembrane mucins MUC1 and MUC16 in epithelial barrier function

PloS One

Noninvasive assessment of tear stability with the tear stability analysis system in tear dysfunction patients

Invest. Ophthalmol. Vis. Sci.

Transforming growth factor beta-1 and beta-2 in human tear fluid

Curr. Eye Res.

A novel method of tear collection: comparison of glass capillary micropipettes with porous polyester rods

Cornea