Abstract
The meibomian gland, the largest sebaceous gland of the body is responsible for the biosynthesis of the lipid layer of the tear film to prevent excessive evaporation. The loss of normal functions of the meibomian gland, known as meibomian gland dysfunction (MGD), is a chronic disease and is the leading cause of dry eye symptoms in clinics. Studies have found sex hormones, especially androgen, play vital roles in the regulation of the functions of the meibomian gland. Recently, androgen has also been preliminarily applied in clinics for the treatment of MGD and showed promising results, especially in people with endogenous androgen deficiency. This review summarized the mechanisms of the function of androgen on the meibomian gland based on molecular, animal, and clinical studies, and proposed evidence-based views about its potential applications for the treatment of MGD.
INTRODUCTION
The meibomian gland, first described by German anatomist Meibom Heinrich in 1666, plays important role in the secretion of lipid and maintenance of tear film stability. The series of glands are located within the upper and lower eyelids and arranged vertically to the lid margin. The terminal ducts connect all acini with the main ducts, and their orifices can be clearly observed at the lid margin. The meibomian glands in the upper eyelids are greater in quantity and length and store twice the amount of lipid of the lower eye lids[1]. The lipid secreted by the meibomian gland is called meibum, which is a complicated mixture of various kinds of lipid molecules. Meibum is critical to the tear film because it covers the surface of the aqueous layer and prevents excessive evaporation[2]. Meibum also has the function of protecting the eye surface from microorganism invasion, assisting tight closure of lid margin during night sleep, and regulating the tension force of the tear film[3]. The role of the meibomian gland is so important that the impairment of its normal function can lead to serious problems. Meibomian gland dysfunction (MGD) is commonly characterized by a chronic, diffuse abnormality of meibomian gland structures, terminal duct obstruction, and qualitative or quantitative changes in lipid secretion. MGD is found to be the leading cause of dry eye disease in clinics, accounting for approximately 40%-60% of dry eye symptoms[4-7]. Patients often suffer from prolonged dryness, burning, and foreign body sensation and may experience impaired quality of life[8]. There are many studies that dig into the pathophysiology of MGD and many factors are believed to play a role in the pathological process of the disease, including congenital abnormalities, decreased blink frequency, chronic inflammation of eye surfaces, and hormonal disturbance[9-13]. However, the pathogenesis of MGD is still poorly understood. Currently, the fundamental therapy for MGD is physical therapy to remove the blockage of gland openings. Many novel therapies are under investigation, including androgen replacement therapy (ART) to be discussed in this review. A thorough understanding of the biological actions of sex hormones on the meibomian gland is the cornerstone for their further applications in clinics. Sex hormones, especially androgen, have been found to be a key regulator of the functions of the meibomian gland[9]. The expression of a variety of genes associated with the biosynthesis, secretion, differentiation, and proliferation processes of the meibomian gland has been found to be regulated by androgen[14-15]. Patients with androgen deficiency are more likely to suffer from MGD than normal people[16]. Many studies found an increased prevalence of MGD in aged people with endogenous androgen deficiency, such as postmenopausal women[17-18]. Recently, androgen has been applied for the treatment of MGD and dry eye disease and demonstrated promising results. This review will summarize currently available findings of androgen and MGD and discuss its clinical practical values.
*EXPRESSION OF ANDROGEN RECEPTORS ON MEIBOMIAN GLAND
*ANDROGEN AND KERATINIZATION
*ANDROGEN AND LIPID BIOSYNTHESIS
*INTERACTION OF ANDROGEN AND OTHER HORMONES
*APPLICATIONS OF ANDROGEN TO TREAT MGD
CONCLUSION
The importance of androgen on the normal functions of the meibomian gland has been illustrated by various studies. Androgen demonstrates extensive actions on lipid biosynthesis, epithelial keratinization, and regulation of the activities of other hormones on the meibomian gland. Androgen has been applied in clinics to treat MGD and showed potential results. However, much is unknown about the optimal formulations of androgen (eye drops, creams, or tablets) and subgroups of people with the greatest responses (age and gender). More studies are needed to further demonstrate the efficacy and safety of the androgen for patients with MGD.
The meibomian gland, the largest sebaceous gland of the body is responsible for the biosynthesis of the lipid layer of the tear film to prevent excessive evaporation. The loss of normal functions of the meibomian gland, known as meibomian gland dysfunction (MGD), is a chronic disease and is the leading cause of dry eye symptoms in clinics. Studies have found sex hormones, especially androgen, play vital roles in the regulation of the functions of the meibomian gland. Recently, androgen has also been preliminarily applied in clinics for the treatment of MGD and showed promising results, especially in people with endogenous androgen deficiency. This review summarized the mechanisms of the function of androgen on the meibomian gland based on molecular, animal, and clinical studies, and proposed evidence-based views about its potential applications for the treatment of MGD.
INTRODUCTION
The meibomian gland, first described by German anatomist Meibom Heinrich in 1666, plays important role in the secretion of lipid and maintenance of tear film stability. The series of glands are located within the upper and lower eyelids and arranged vertically to the lid margin. The terminal ducts connect all acini with the main ducts, and their orifices can be clearly observed at the lid margin. The meibomian glands in the upper eyelids are greater in quantity and length and store twice the amount of lipid of the lower eye lids[1]. The lipid secreted by the meibomian gland is called meibum, which is a complicated mixture of various kinds of lipid molecules. Meibum is critical to the tear film because it covers the surface of the aqueous layer and prevents excessive evaporation[2]. Meibum also has the function of protecting the eye surface from microorganism invasion, assisting tight closure of lid margin during night sleep, and regulating the tension force of the tear film[3]. The role of the meibomian gland is so important that the impairment of its normal function can lead to serious problems. Meibomian gland dysfunction (MGD) is commonly characterized by a chronic, diffuse abnormality of meibomian gland structures, terminal duct obstruction, and qualitative or quantitative changes in lipid secretion. MGD is found to be the leading cause of dry eye disease in clinics, accounting for approximately 40%-60% of dry eye symptoms[4-7]. Patients often suffer from prolonged dryness, burning, and foreign body sensation and may experience impaired quality of life[8]. There are many studies that dig into the pathophysiology of MGD and many factors are believed to play a role in the pathological process of the disease, including congenital abnormalities, decreased blink frequency, chronic inflammation of eye surfaces, and hormonal disturbance[9-13]. However, the pathogenesis of MGD is still poorly understood. Currently, the fundamental therapy for MGD is physical therapy to remove the blockage of gland openings. Many novel therapies are under investigation, including androgen replacement therapy (ART) to be discussed in this review. A thorough understanding of the biological actions of sex hormones on the meibomian gland is the cornerstone for their further applications in clinics. Sex hormones, especially androgen, have been found to be a key regulator of the functions of the meibomian gland[9]. The expression of a variety of genes associated with the biosynthesis, secretion, differentiation, and proliferation processes of the meibomian gland has been found to be regulated by androgen[14-15]. Patients with androgen deficiency are more likely to suffer from MGD than normal people[16]. Many studies found an increased prevalence of MGD in aged people with endogenous androgen deficiency, such as postmenopausal women[17-18]. Recently, androgen has been applied for the treatment of MGD and dry eye disease and demonstrated promising results. This review will summarize currently available findings of androgen and MGD and discuss its clinical practical values.
*EXPRESSION OF ANDROGEN RECEPTORS ON MEIBOMIAN GLAND
*ANDROGEN AND KERATINIZATION
*ANDROGEN AND LIPID BIOSYNTHESIS
*INTERACTION OF ANDROGEN AND OTHER HORMONES
*APPLICATIONS OF ANDROGEN TO TREAT MGD
CONCLUSION
The importance of androgen on the normal functions of the meibomian gland has been illustrated by various studies. Androgen demonstrates extensive actions on lipid biosynthesis, epithelial keratinization, and regulation of the activities of other hormones on the meibomian gland. Androgen has been applied in clinics to treat MGD and showed potential results. However, much is unknown about the optimal formulations of androgen (eye drops, creams, or tablets) and subgroups of people with the greatest responses (age and gender). More studies are needed to further demonstrate the efficacy and safety of the androgen for patients with MGD.
