The tarsal glands of Meibom (glandulae tarsales) are large sebaceous glands located in the eyelids and, unlike those of the skin, are unassociated with hairs. According to Duke-Elder and Wyler,1 they were first mentioned by Galenus in 200 AD and later, in 1666, they were described in more detail by the German physician and anatomist Heinrich Meibom, after whom they are named.

Lipids produced by the meibomian glands are the main component of the superficial lipid layer of the tear film that protects it against evaporation of the aqueous phase and is believed also to stabilize the tear film by lowering surface tension.2 Hence, meibomian lipids are essential for the maintenance of ocular surface health and integrity.

Although they share certain principal characteristics with ordinary sebaceous glands, they have several distinct differences in anatomy, location, secretory regulation, composition of their secretory product, and function.

Functional disorders of the meibomian glands, referred to today as meibomian gland dysfunction (MGD),3 are increasingly recognized as a discrete disease entity.4–8 In patients with dry eye disease, alterations in the lipid phase that point to MGD are reportedly more frequent than isolated alterations in the aqueous phase. In a study by Heiligenhaus et al.,9 a lipid deficiency occurred in 76.7% of dry eye patients compared with only 11.1% of those with isolated alterations of the aqueous phase. This result is in line with the observations by Shimazaki et al.10 of a prevalence of MGD in the absolute majority of eyes with ocular discomfort defined as dry eye symptoms. These observations noted that 64.6% of all such eyes and 74.5% of those excluding a deficiency of aqueous tear secretion were found to have obstructive MGD, or a loss of glandular tissue, or both.10 Horwath-Winter et al.11 reported MGD in 78% of dry eye patients or, if only non-Sjogren patients are considered, in 87% compared with 13% with isolated aqueous tear deficiency. It may thus be accepted that MGD is important, conceivably underestimated, and possibly the most frequent cause of dry eye disease due to increased evaporation of the aqueous tears.5,9–12

After some excellent reviews of MGD4,7,8,13,14 in the past, many new findings have been reported in recent years, and other questions remain to be identified and resolved. A sound understanding of meibomian gland structure and function and its role in the functional anatomy of the ocular surface15 is needed, to understand the contribution of the meibomian glands to dysfunction and disease. Herein, we seek to provide a comprehensive review of physiological and pathophysiological aspects of the meibomian glands.

/pdf/the-international-workshop-on-meibomian-gland-dysfunction-1rohh1kg6i.pdf

The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on Anatomy, Physiology, and Pathophysiology of the Meibomian Gland

Tendons and ligaments: A morphological and biochemical comparison

Objective. We have recently discovered that women with primary and secondary Sjogren's syndrome are androgen-deficient. We hypothesize that this hormone insufficiency contributes to the meibomian gland dysfunction, tear film instability, and evaporative dry eye that are characteristic of this autoimmune disorder. If our hypothesis is correct, we predict: (1) that androgens regulate meibomian gland function, control the quality and/or quantity of lipids produced by this tissue, and promote the formation of the tear film's lipid layer; and (2) that androgen deficiency, due to an attenuation in androgen synthesis (e.g., during Sjogren's syndrome, menopause, aging, complete androgen-insensitivity syndrome [CAIS] and anti-androgen use), will lead to meibomian gland dysfunction and evaporative dry eye. The following studies were designed to test these predictions. Methods. Experimental procedures included clinical studies, animal models, and histological, biochemical, molecular biological, and biomedical engineering techniques. Results. Our results demonstrate that: (1) androgens regulate the meibomian gland. This tissue contains androgen receptor mRNA, androgen receptor protein within acinar epithelial cell nuclei, and Types 1 and 2 5α-reductase mRNAs. Moreover, androgens appear to modulate lipid production and gene expression in mouse and/or rabbit meibomian glands; and (2) androgen deficiency may lead to meibomian gland dysfunction, altered lipid profiles in meibomian gland secretions, tear film instability, and evaporative dry eye. Thus, we have found that anti-androgen therapy in men is associated with meibomian gland disease, a decreased tear film breakup time, and functional dry eye. Furthermore, we have discovered that androgen receptor dysfunction in women with CAIS is associated with meibomian gland changes and a significant increase in the signs and symptoms of dry eye. Of interest, we have also found that androgen deficiency is associated with significant and striking alterations in the neutral and polar lipid patterns of human meibomian gland secretions. Conclusions. Our findings show that the meibomian gland is an androgen target organ and that androgen deficiency may promote meibomian gland dysfunction and evaporative dry eye. Overall, these results support our hypothesis that androgen deficiency may be an important etiologic factor in the pathogenesis of evaporative dry eye in women with Sjogren's syndrome.

Androgen Deficiency, Meibomian Gland Dysfunction, and Evaporative Dry Eye

Eukaryotes are characterized by endomembranes that are connected by vesicular transport along secretory and endocytic pathways. The compositional differences between the various cellular membranes ...

https://www.physiology.org/doi/pdf/10.1152/physrev.2001.81.4.1689

The organizing potential of sphingolipids in intracellular membrane transport

Sialic acids are cytoprotectors, mainly localized on the surface of cell membranes with multiple and outstanding cell biological functions. The history of their structural analysis, occurrence, and functions is fascinating and described in this review. Reports from different researchers on apparently similar substances from a variety of biological materials led to the identification of a 9-carbon monosaccharide, which in 1957 was designated "sialic acid." The most frequently occurring member of the sialic acid family is N-acetylneuraminic acid, followed by N-glycolylneuraminic acid and O-acetylated derivatives, and up to now over about 80 neuraminic acid derivatives have been described. They appeared first in the animal kingdom, ranging from echinoderms up to higher animals, in many microorganisms, and are also expressed in insects, but are absent in higher plants. Sialic acids are masks and ligands and play as such dual roles in biology. Their involvement in immunology and tumor biology, as well as in hereditary diseases, cannot be underestimated. N-Glycolylneuraminic acid is very special, as this sugar cannot be expressed by humans, but is a xenoantigen with pathogenetic potential. Sialidases (neuraminidases), which liberate sialic acids from cellular compounds, had been known from very early on from studies with influenza viruses. Sialyltransferases, which are responsible for the sialylation of glycans and elongation of polysialic acids, are studied because of their significance in development and, for instance, in cancer. As more information about the functions in health and disease is acquired, the use of sialic acids in the treatment of diseases is also envisaged.

/pdf/exploration-of-the-sialic-acid-world-37d4w0kjhu.pdf

Exploration of the Sialic Acid World.

Quantitative analysis of brain galactosylceramides by high performance liquid chromatography of their perbenzoyl derivatives.

Preparation and analysis of benzoylated cerebrosides

The glycosphingolipids are derivatives of N-acylsphingosines (ceramide) to which a carbohydrate unit, composed of one or more glycosyl moieties, is bound glycosidically in a β linkage to the hydroxyl at carbon 1 of sphingosine. The gangliosides are glyco-sphingolipids which contain one or more sialic acid residues as one of the glycosyl moieties (1). Gangliosides occur in most organs and body fluids but their highest concentration is in the central nervous system. The brain gangliosides are primarily located in neuronal dendritic processes and different brain areas have significantly different complements of the various gangliosides. Analyses of subcellular fractions have revealed that the ganglioside content of nuclei, mitochondria and synaptic vesicles is low while microsomes and synaptic membranes contain the highest amount of gangliosides. Thus gangliosides appear to be neuronal membrane components and perhaps participate in the complex molecular events at the synapse which are necessary for information processing. The combination of a large hydrophilic moiety with a strongly charged sialic acid and the hydrophobic ceramide portion suggest that gangliosides are membrane components which are suited for interaction with the microenvironment. It is possible that interaction of gangliosides with cations could lead to changes in the molecule which would in turn produce changes in the properties of the synaptic membrane. Calcium has a pronounced effect on the solubility of gangliosides. Reactions which would alter the number of negative charges in a ganglioside molecule such as formation of an ester could conceivably play an important role in modification of synaptic membrane properties.

Ganglioside Inner Esters

The expression of neutral glycosphingolipids was examined in primary kidney cell cultures derived from adult male and female beige mutant mice (C57BL/6J;bgj/bgj) with enrichment for proximal tubule cells during preparation of explants and using defined serum-free medium for the culture conditions. Cell proliferated for 7 daysin vitro to provide confluent or nearly confluent monolayers of epithelial-type growth indicative of proximal tubule cells. The malevs female differences in neutral glycosphingolipids seen in the kidneyin vivo were retained in these 7 day cultures. Cultures derived from males contained galacto- and digalactosylceramides whereas those from females did not express these types of glycolipids. Also, male cells had higher ratios of sphingosine: phytosphingosine containing species in Nfa (non-hydroxy fatty acid) globotriaosylceramide and in glucosylceramide than females. The shift in sphingosine: phytosphingosine to male ratios in Nfa globotriaosylceramide and in glucosylceramide could be stimulated in female kidney cells by treatment with 10−5 M testosterone or 5α-dihydrotestosterone. The male-specific expression of neutral glycosphingolipids, then, appears to be stable character of male-type differentiation in mouse kidney that is passed on during proliferation in culture. Female kidney cells retain an ability to respond to androgens with specific changes in neutral glycosphingolipid expression during 7 days of growthin vitro in serum-free conditions, but do not respond with the induction of the male-specific glycolipids galacto-and digalactosylceramides as seenin vivo.

Expression of glycosphingolipids in serum-free primary cultures of mouse kidney cells: male-female differences and androgen sensitivity

A high performance liquid chromatographic (HPLC) method for analysis of galactosylceramides as their benzoyl derivatives has been devised. Samples con- taining 10- 150 nmoles of monohexosylceramides are benzoylated by heating for 60 min at 60°C in 0.5 ml of 10% (v/v) benzoyl chloride in pyridine. The products are purified by solvent distribution and analyzed by HPLC. The benzoylated cerebrosides with nonhydroxy fatty acids are separated from those with hydroxy fatty acids on a Zipax column with 7% ethyl acetate in hexane as a solvent and UV absorption at 280 nm is recorded. This isocratic procedure can be applied directly to chloroform-methanol extracts of adult brain with a relative standard deviation of 3.0% for cerebrosides with nonhydroxy fatty acids and 4.0% for cerebrosides with hydroxy fatty acids. Sulfatides do not interfere in the assay and can be converted to cerebrosides after desulfation by mild acid methanolysis. Benzoylated glucosyl- and galactosylceramides can be sepa- rated on a MicroPak NH2 column with 1.5% 2-propanol in cyclopentane as the chromatographic solvent.

Q u anti tat ive anal y s i s of b r ai n g al act osy I ce ram id es by high performance liquid chromatography of the i r per benzoyl d er ivat ives

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