Understanding MGD Through the Lens of Sebaceous Gland Dysfunction

Meibomian gland dysfunction (MGD) is a common condition in which the meibomian glands, specialized sebaceous glands in the eyelids, fail to produce sufficient quantities and/or quality of meibum, resulting in evaporative dry eye and discomfort. Understanding sebaceous gland disorders offers valuable insights into MGD, as both meibomian and sebaceous glands share a physiological basis—both secrete oily substances essential for maintaining local tissue health and function. In this article, I discuss the anatomy and physiology of these glands and explain their role in MGD.

SEBACEOUS GLANDS

Sebaceous glands are holocrine glands with short ducts that open into hair follicles, enabling sebum to reach the skin. Located in the dermis and epidermis, sebaceous glands form grape-like clusters and consist of acinar cells that accumulate sebum. Eventually, the acinar cells rupture within a small alveolar duct that connects to a central duct, releasing sebum onto the skin through the hair follicle.¹ This process requires continuous turnover, proliferation, and differentiation of cells within the acini.²

Sebaceous glands are widespread throughout the body and are found in the skin, except on the palms of hands and soles of feet.³ Although most sebaceous glands are associated with pilosebaceous units in hair follicles, a small subset, called free sebaceous glands, includes structures such as the meibomian and tarsal glands of the eyelids.

Sebum, derived from a Latin word meaning “tallow,” or rendered fat,⁴ is primarily composed of triglycerides, free fatty acids, cholesterol, wax esters, squalene, and diglycerides.⁵ Sebum is produced by sebocytes and released into the ductal system through holocrine secretion, where the entire contents of the cell are discharged during apoptosis. The average rate of sebum production is 1 mg/10 cm² every 3 hours.⁶ Insufficient sebum production can lead to gland stasis and associated dryness; overproduction results in oily skin.⁷

Sebum serves multiple essential functions, including lubricating the skin and hair, enhancing water resistance, supporting thermoregulation, facilitating local androgen synthesis, and mitigating sweat evaporation.⁷ Sebum has antimicrobial, antiinflammatory, and antioxidant properties.^7,8 One of its primary mechanisms for supporting immunity is through the formation of the acid mantle, an acidic film (pH 4.5-6.2) that protects against alkaline pathogens.⁹

The composition of sebum can be altered by various proinflammatory or antiinflammatory cytokines, interleukins, chemokines, pheromones, and free fatty acids in response to stimuli such as Propionibacterium acnes, defensins, or cathelicidins.⁷ Sebaceous follicles also harbor a rich population of bacteria (eg, Propionibacterium acnes and Staphylococcus epidermidis), fungi, and Demodex folliculorum mites.⁴

Age- and Sex-Related Changes

Sebum production is primarily regulated by androgens, particularly 5α-dihydrotestosterone. For this reason, there is a significant increase in sebum production at birth and during puberty, followed by relative stability in early adulthood. However, production eventually declines to nearly zero in postmenopausal women and men 70 years of age and older.¹⁰ In fact, sebum production decreases by an average of 23% in males and 32% in females every decade after adolescence.¹¹ Increased androgen activity in men accounts for the approximately 10% difference in sebum production between the sexes.¹¹

Sebaceous glands tend to increase in size with age. Interestingly, while new sebaceous glands typically do not form after birth, stem cell differentiation can lead to gland rejuvenation in the case of damage.¹²

MEIBOMIAN GLANDS

As noted, meibomian glands are specialized sebaceous glands. More specifically, they are highly specialized, free sebaceous holocrine glands that exhibit all the histological characteristics and embryologic development of sebaceous glands, but they differ in morphology and lipid composition.³ The upper eyelids contain 30 to 40 individual meibomian glands, while the lower eyelids have approximately 25 glands.¹³ The central duct of a meibomian gland resembles a hair follicle but lacks a hair shaft.²

Meibomian glands are generally smaller than pilosebaceous glands but contain a greater number of secretory acini, particularly in the upper eyelid.³ The muscle of Riolan, a ciliary bundle in the palpebral part of the orbicularis oculi, is thought to compress the meibomian glands during blinking, aiding in meibum secretion.¹⁴ Similar to sebocytes, meibocytes release meibum via holocrine secretion or cell apoptosis. To replenish meibocytes, each meibomian gland contains specialized stem cells.¹⁴

Meibum Versus Sebum Composition

The composition of meibum is unique, containing a distinct blend of neutral lipids not found elsewhere in the body (Figure). Like the lipid-rich sebum produced by sebaceous glands, meibum is generated by meibomian glands. Meibum is continuously produced by acini and released at the terminal ductule onto the lid margin and ocular surface through mechanical force during blinking.¹⁵ Meibum comprises more than 600 lipids and 90 different proteins, along with various types of keratin.¹⁵ It differs from sebum in that meibum contains a more complex mixture of polar and nonpolar lipids, including free cholesterol, diesters, ceramides, triglycerides, phospholipids, and free fatty acids.³

Meibum has lower levels of triglycerides, diglycerides, and squalene, as well as longer-chain wax esters. This specialized composition is tailored for the ocular surface. Notably, there is no difference in composition between men and women.³ Healthy meibum has a melting point below body temperature to maintain low viscosity. However, the melting point of meibum can vary based on its lipid composition and the degree of keratinization.¹⁴

Hyperkeratinization

One key similarity between meibomian and sebaceous glands is their ability to undergo keratinization, a significant factor in both MGD and sebaceous gland dysfunction.^2,15 Although hyperkeratinization has been extensively studied and treated in skin disorders, its relevance to MGD is just beginning to be explored.

Hyperkeratinization occurs when there is excessive formation and accumulation of keratin due to inadequate desquamation.¹⁶ Research indicates that under inflammatory conditions and oxidative stress, disulfide bond formation can crosslink keratin, leading to the formation of aggregates in meibum and excessive keratinization of the central duct and orifices.¹⁵ Similar to acne, this process results in thickened meibum, the formation of a plug, and obstruction resulting from accumulated keratinized material.¹⁷ Obstruction caused by hyperkeratinization is considered a major driver of MGD.¹⁷

Even a 10% increase in keratin concentration in meibum can elevate surface pressure and rigidity, causing dilation of the central duct from cell debris and sebaceous material, which destabilizes the lipid layer of the tear film.^18,19 Furthermore, increased keratin concentration raises the melting point of meibum, resulting in higher viscosity, stasis, and waxy secretions at body temperature. In a hyperkeratinized state, with disulfide bond formation, the melting point of meibum can reach as high as 300°, which is unsafe for humans.¹⁵ This phenomenon may explain why warm compresses are often ineffective in treating certain forms of MGD, as they cannot overcome the increased melting point.

THE MORE YOU KNOW

MGD and sebaceous gland disorders share a common physiological basis, both involving the secretion of lipids essential for maintaining tissue health. The dysfunction of these glands, particularly through processes like hyperkeratinization, leads to the disruption of lipid volume and quality, resulting in conditions such as evaporative dry eye. Understanding the similarities between sebaceous and meibomian glands, including their secretion processes and the effects of factors like inflammation and oxidative stress, provides valuable insights into the pathophysiology of MGD.

In the next and final part of this series, I’ll discuss treatments for disorders of sebaceous and meibomian glands, highlighting similarities between the two.

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