The Harderian gland, also known as the third eyelid gland, is an accessory lacrimal gland found within the orbit behind the third eyelid (nictitating membrane) of many vertebrates. Though the functional role of the Harderian gland was long unclear, research over the past few decades has helped to elucidate its purpose. The gland secretes a lipid-rich substance called meibum which contributes to tear film and helps lubricate and protect the eye. Additionally, the Harderian gland contains immune cells and contributes to immune surveillance and defense within the eye. This article will provide an overview of the anatomy, histology, and function of the Harderian gland.
Anatomy and Histology of the Harderian Gland
The Harderian gland is elongated in shape and pale pink or yellow in color. It extends from the back of the orbit to lie within and behind the third eyelid. The gland consists primarily of tubular glands comprised of two main cell types:
- Serous cells: These cells produce a watery secretion containing proteins and electrolytes
- Lipid-secreting cells: These cells produce a lipid-rich meibum composed of cholesterol, cholesterol esters, and phospholipids
In some species like rodents, the Harderian gland contains a large number of plasma cells and lymphocytes and takes on the appearance of lymphoid tissue. The gland is encapsulated and receives sympathetic innervation. In terms of vascular supply, the Harderian gland has an extensive capillary network and is highly vascularized.
Meibum Production
One of the main functions of the Harderian gland is producing meibum, the oily substance that contributes to the tear film. Meibum helps prevent tear evaporation and provides a smooth optical surface for the eye. The lipid-secreting cells of the Harderian gland produce meibum and secrete it through the ducts of the gland onto the surface of the third eyelid. When the third eyelid blinks, it spreads the meibum across the eye.
Meibum is composed mainly of nonpolar lipids including cholesterol, cholesterol esters, and phospholipids. However, it also contains over 900 different proteins, antimicrobial peptides, and other substances. The exact composition of meibum varies between species. For example, the meibum of cattle contains phospholipids and cholesterol derivatives not found in humans. The lipid and protein composition of meibum helps it reduce tear film evaporation, inhibit bacterial growth, and provide a smooth optical surface.
Contribution to Tear Film
The meibum secreted by the Harderian gland mixes with the aqueous tears secreted by the main lacrimal gland and conjunctiva. This mixture forms the outermost lipid layer of the tear film that coats the surface of the eye. Along with the inner mucous layer, the lipid layer prevents rapid tear evaporation and helps maintain tear film integrity between blinks.
Rather than evenly coating the tear film surface, the lipids secreted by the Harderian gland form a complex meshwork. This allows for some areas of the tear film to remain permeable to oxygen while reducing water loss. Blinking spreads the meibum, creating a smooth lipid surface across the eye. The lipid layer also provides a hydrophobic barrier that reduces eyelid friction during blinking.
Abnormalities in meibum quantity or quality can disrupt the tear film and contribute to dry eye disease. Harderian gland removal in animal models leads to increased tear evaporation and ocular surface damage. Thus, Harderian gland secretions play an indispensible role in tear film health and protecting the ocular surface.
Immune System Functions
In addition to its role in tear film production, the Harderian gland contributes to immune protection of the eye. The gland contains large numbers of lymphocytes, plasma cells, macrophages, eosinophils, and mast cells. Plasma cells produce immunoglobulin A antibodies which are secreted in the glandular meibum and provide defense against ocular pathogens.
The Harderian gland responds to infectious stimuli by recruiting immune cells from the bloodstream into the glandular tissue. Inflammatory mediators triggered during infection also stimulate the gland to increase lipocalin production. Lipocalins have antimicrobial properties that help fight infection.
By secreting antimicrobial proteins and immunoglobulins onto the ocular surface, the Harderian gland provides an important immunological barrier. The gland exhibits changes during inflammatory ocular surface disorders and systemic autoimmune conditions. Harderian gland inflammation may exacerbate dry eye disease through alterations in lipid secretions. Modulating the immune activity of the Harderian gland could potentially help manage certain ocular conditions.
Species Variations
While the Harderian gland is found in most terrestrial vertebrates, its size and functional importance varies between species:
- Rodents: The gland is very large, accounts for 1% of body weight, and takes on a lymphoid tissue appearance.
- Cats: The gland is moderately sized and connects to the nasolacrimal duct.
- Dogs: A small vestigial gland is present behind the third eyelid.
- Rabbits: The gland is colorless; meibum secretion spreads onto eyes during third eyelid blinking.
- Birds: A small Harderian gland is found only in some species.
- Reptiles: The gland is lacking in adult reptiles but exists during larval development.
- Humans: A small Harderian gland remnant may exist but the function is unknown.
In species like cows and rodents, the voluminous Harderian gland contributes the majority of the lipids to the tear film. In other species, meibum secretion represents just a small fraction of the overall tear film. The gland is largest in animals that possess a third eyelid capable of spreading secretions over the eye during blinking.
Development
The Harderian gland originates from epithelial tissue during embryonic development. In mice, early growth and branching of the glandular tissue is dependent on signaling through the FGF10 receptor. Nerve innervation and vascularization help drive further maturation of the glandular lobules before birth.
Birth triggers rapid growth of the Harderian gland over the first few weeks of life. The gland increases in size due to epithelial cell proliferation and differentiation rather than cell hypertrophy. Full secretory capability is attained around two weeks after birth in mice. In humans, the Harderian gland regresses before birth and leaves only small vestigial remnants. The factors that drive loss of the gland in humans are not fully understood.
Clinical Relevance
Although the Harderian gland does not play a major role in human physiology, it has some important clinical associations:
- Dry eye disease: Dysfunction of the small Harderian gland remnant may contribute to tear film abnormalities in some patients.
- Infection: The Harderian gland can be involved in cases of viral conjunctivitis, toxoplasmosis, tuberculosis and other ocular infections.
- Neoplasia: Benign and malignant tumors arising from the Harderian gland occur in many species and can cause ocular distortions or metastasis.
- Proptosis: In cats, dogs and mice, swelling of the gland can displace the eye forward out of the orbit (proptosis).
- Drug testing: Harderian gland atrophy in rodents can serve as a biomarker for toxicological studies.
- Immunology: Alterations in plasma cells, immunoglobulins, and lipids occur in autoimmune conditions like Sjogren’s syndrome.
Surgical removal of the Harderian gland is sometimes performed in animals to treat glandular tumors, proptosis, or chronic conjunctivitis. The procedure may be done in combination with third eyelid removal (nictectomy). Most animals can compensate for Harderian gland removal through secretion of lipids from other accessory lacrimal glands.
Conclusion
In summary, the Harderian gland is an orbital lacrimal gland found within the third eyelid of many vertebrates. Its main functions include:
- – Producing meibum – a lipid-rich substance that contributes to the tear film
- – Lubricating and protecting the ocular surface
- – Supplying antimicrobial and immunological defenses to the eye
- – Potentially supplementing the tear film in humans
While not critical for vision, the Harderian gland plays an important supplemental role in maintaining eye health through its secretion of tear film components and immune factors. Continued research on this fascinating gland will further elucidate its biological functions and clinical relevance across vertebrate species.