Cell size and nucleo-cytoplasmic ratios of meibocytes in the anterior acini of the upper eyelid Meibomian glands in rabbits.

OBJECTIVE: To assess the morphological details of the acini of the normal meibomian gland. ANIMALS STUDIED: Six young adult pigmented rabbits. METHODS: The upper eyelid was prepared in extended configuration by glutaraldehyde fixation. Tissue block sections approximately 0.5-1 mm from the eyelid margin were assessed by light microscopy in sagittal sections and transmission electron microscopy (TEM) in coronal sections. TEM images at between 1000× and 2000× magnification were enlarged onto A3-sized prints and cell size and nuclei measured by planimetry. RESULTS: Light microscopy sagittal sections revealed clusters of variable sized acini, sometimes appearing to be slightly overlapping and without any obvious spatial organization of the internal cells (meibocytes). The estimated areas of the acini were close to 6500 sq micron. Coronal sections, as examined by TEM, allowed for visualization of small to large acini (average diameter 82 ± 17 microns, with an estimated area of 5500 sq. microns) containing variable numbers of immature (partly differentiated) or mature (fully differentiated) meibocytes with a distinct spatial organization. The average area of the meibocytes was 158 ± 81 square microns, and they usually appeared to have a single nucleus (with an average sectional area of 29 ± 12 square microns). Within individual acini, peripherally located immature meibocytes tended to be smaller and have higher nucleo-cytoplasmic area ratios, while more centrally mature located meibocytes tended to be slightly larger and had lower or much lower nucleocytoplasmic ratios. CONCLUSIONS: Comparative studies on meibomian glands can be undertaken with objective assessments to assess for normality or abnormality.

Meibomian gland cells display a differentiation-dependent composition of desmosomes.

Meibomian glands are a modified type of sebaceous glands within the eye lid, which produce an oily secretion important for the stabilization and the prevention of evaporation of the tear film. The holocrine secretory mode of Meibomian glands is characterized by the centripetal movement, the maturation and finally degeneration of the acinar epithelial cells. The process of maturation and degeneration is paralleled by altered expression pattern of certain proteins and the intracellular accumulation of Meibomian gland lipids. In this study, we investigated the correlation between the differentiation status of Meibomian acinus cells and the presence of adhesive junctions. By ultrastructural analyses, we showed for the first time that the frequency of desmosomes increased with the degree of differentiation. Importantly, we detected a differentiation-dependent distribution pattern of desmosomes within the Meibomian gland cells of the acinus, whereas molecules of other cell junctions, e.g., adherens junctions, are equally distributed. Together, these findings provide new insights into the processes of Meibomian gland secretion and may be important for the interpretation of Meibomian gland dysfunction causing diseases like the dry eye syndrome.

In vitro effects of sex hormones in human meibomian gland epithelial cells.

Meibomian gland dysfunction (MGD) is considered the most common cause of dry eye disease (DED). Sex hormones seem to play a role in the pathogenesis of MGD although their involvement is not completely understood. Therefore, in the present study we evaluated the effect of dihydrotestosteron (DHT) and estradiol (ß-Est) on an immortalized human meibomian gland epithelial cell line (HMGEC). Protein expression of sex hormone receptors in HMGEC was investigated by western blot. Ultrastructural morphology, Sudan III lipid staining, cell proliferation as well as vitality assays were performed. Furthermore, expression of MGD-associated markers for keratinization (hornerin, involucrin and CK6), proliferation (CK5 and CK14) and lipid synthesis (fatty acid synthase and stearoyl-CoA desaturase) were analyzed by real time RT-PCR. Western blot revealed presence of androgen receptor (AR), estrogen receptors α and -ß (ERα, ERß) and progesterone receptor (PR) in HMGEC. PR, ERα and ERß expression was significantly induced under cultivation with serum, whereas sex hormones stimulation showed no further effect on protein expression of PR, ERα and ERß. Our results showed no impact of MGD-associated sex hormones to cellular morphology and lipid accumulation in HMGEC. Cell proliferation was slightly induced through application of sex hormones and supplementation of calcium. However, both sex hormones and calcium altered gene expression of MGD-associated markers. Especially keratinization genes hornerin (HRNR) and cornulin (COR) were induced after application of sex hormones and calcium in serum-free cultivated HMGEC. This may promote keratinization processes that are associated with MGD. Further investigations are necessary to analyze the (hyper)keratinization processes that occur during MGD and using HMGEC as an in vitro model.

Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy.

PURPOSE: To evaluate the morphological changes of the meibomian glands (MGs) using in vivo laser confocal microscopy (CM) in dry eye (DE) patients with chronic graft-versus-host disease (cGVHD). METHODS: Seventeen eyes from 9 patients with a diagnosis of DE associated with cGVHD (DE/cGVHD group; 6 males, 3 females; median 50.5 years) and 16 eyes of 8 hematopoietic stem cell transplantation (HSCT) recipients without DE (non-DE/non-cGVHD group; 5 males, 3 females; median 47.0 years) were enrolled. CM was used to investigate the MG and MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), and the fibrosis grade. Clinical findings of the lid margin were obtained. Tear dynamics, ocular surface vital staining, meibography, and MG expressibility were also examined. Data were compared between the 2 groups using the unpaired t and Mann-Whitney tests. RESULTS: The mean MGAUD value was significantly lower in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.01, 57.8±38.3 glands/mm(2), 88.8±26.6 glands/mm(2), respectively), and the mean MGALD and MGASD were significantly shorter in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.0018, 37.3±24.4 µm and 60.4±11.8 µm, p=0.0106, 17.7±11.8 µm and 26.6±6.03 µm, respectively). The mean fibrosis grade was significantly higher in the DE/cGVHD group than the non-DE/non-cGVHD group (p<0.0001, 1.39±0.71 grade, 0.06±0.25 grade, respectively). Clinical findings in the lid margin, tear dynamics, and ocular surface findings were significantly worse in the DE/cGVHD group than in the non-DE/non-cGVHD group. CONCLUSIONS: CM clearly depicted the morphological changes of the MG in the DE/cGVHD group, and revealed the severity of the meibomian gland dysfunction. Patients with severe DE after HSCT showed atrophic MG and excessive fibrosis.

[Tarsal gland of the ticks Ixodes persulcatus and Ixodes ricinus (Ixodidae)].

A complicated multicellular gland is situated in tarsi of all the legs, occupying one third to half of the segment. Glandular cells form a single-layer sack; inner surface of the sack (gland cavity) is enveloped by a multilayer membrane. Cuticular rods connecting muscles with the claw pass inside this cavity. Glandular cells are characterized by the presence of numerous apical microvilli associated with accumulations of mitochondria, and secretory vacuoles enclosed in cellular membranes. The basal part of each cell contains lipid vacuoles and glycogen granules. The possibility of the track contact pheromone's production by the tarsal gland is discussed.

Histological and immunohistochemical characterization of the porcine ocular surface.

The ocular surface of the white domestic pig (Sus scrofa domestica) is used as a helpful model of the human ocular surface; however, a complete histological description has yet to be published. In this work, we studied porcine eyeballs with intact eyelids to describe and characterize the different structures that form the ocular surface, including the cornea and conjunctiva that covers the bulbar sclera, tarsi, and the nictitating membrane. We determined the distribution of goblet cells of different types over the conjunctiva and analyzed the conjunctival-associated lymphoid tissue (CALT). Porcine eyeballs were obtained from a local slaughterhouse, fixed, processed, and embedded in paraffin blocks. Tissue sections (4 µm) were stained with hematoxylin/eosin, Alcian blue/Periodic Acid Schiff, and Giemsa. Slides were also stained with lectins from Arachis hypogaea (PNA) and Helix pomatia (HPA) agglutinins and immunostained with rabbit anti-CD3. We found that the porcine cornea was composed of 6-8 epithelial cell layers, stroma, Descemet's membrane, and an endothelial monolayer. The total corneal thickness was 1131.0±87.5 µm (mean±standard error of the mean) in the center and increased to 1496.9±138.2 µm at the limbus. The goblet cell density was 71.25±12.29 cells/mm, ranging from the highest density (113.04±37.21 cells/mm) in the lower palpebral conjunctiva to the lowest density (12.69±4.29 cells/mm) in the bulbar conjunctiva. The CALT was distributed in the form of intraepithelial lymphocytes and subepithelial diffuse lymphoid tissue. Lenticular-shaped lymphoid follicles, about 8 per histological section, were also present within the conjunctival areas. In conclusion, we demonstrated that the analyzed porcine ocular structures are similar to those of humans, confirming the potential usefulness of pig eyes to study ocular surface physiology and pathophysiology.

In vivo findings of the bulbar/palpebral conjunctiva and presumed meibomian glands by laser scanning confocal microscopy.

OBJECTIVE: To report in vivo laser scanning confocal microscopic findings of the normal human conjunctiva and presumed meibomian glands and to investigate the potential application of this confocal microscope (HRT II Rostock Cornea Module) as a diagnostic device for normal and abnormal ocular surface structures. METHOD: Four healthy volunteers (51-, 49-, 31-, and 30-year-old men) participated in this study. The temporal bulbar conjunctiva, approximately 5 mm away from the limbus, and the upper tarsus conjunctiva of each patient were examined in vivo by a laser confocal microscope. Also, presumed meibomian glands beneath the tarsal conjunctiva were examined. RESULTS: In all subjects, the in vivo laser confocal microscope obtained similar images. In the superficial epithelial cell layer of the bulbar conjunctiva, numerous bright nuclei were observed. We also observed many Langerhans cells with characteristic dendritic morphology and goblet cells with relatively homogeneous brightness in the bulbar conjunctiva. Most interestingly, the palpebral conjunctival epithelium with invaginations or crypts was observed. In addition, weblike structures, presumably meibomian glands, were observed beneath the palpebral conjunctival epithelium. CONCLUSIONS: These results indicate that in vivo laser confocal microscopy can be used not only to visualize the bulbar conjunctiva but the upper tarsus conjunctiva and possibly subconjunctival meibomian glands. Further investigations of conjunctival and meibomian gland pathologies may further elucidate the potential of this device in clinical ophthalmology.

Effects of 13-cis-retinoic acid on the hamster meibomian gland.

Systemic administration of 13-cis-retinoic acid caused a reduction of acinar tissue in the hamster meibomian gland. Histologic examination of treated meibomian gland tissue revealed a thickening of gland ductal epithelium and a decrease in the numbers of mature lipid-laden acinar cells. Morphometric analysis showed a reduction of up to 75% in mean volume of meibomian acinar tissue from animals fed a high dose of 13-cis-retinoic acid. Clinical observations in these animals included alopecia and weight loss. Ocular complications included crusting of the eyelid margin and the external surface of the lid and erythema of the conjunctiva. The model supports previous observations by the authors that systemic 13-cis-retinoic acid affects meibomian gland structure in a laboratory animal. The ocular side effects described in this model suggest that future functional studies may yield important insights into the complex relationship between meibomian gland morphology and function, and events on the ocular surface.

Human meibomian glands: the ultrastructure of acinar cells as viewed by thin section and freeze-fracture transmission electron microscopies.

Heightened interest in meibomian glands dysfunction prompted the authors to examine the ultrastructure of the glandular epithelium in specimens of surgical origin, by thin section and freeze-fracture electron microscopies. In meibomian glands, the morphology and ultrastructure of acinar cells varies considerably according to their stage of holocrine differentiation. This study shows close interdependence between fat droplets and Golgi apparatus or endoplasmic reticulum. As the cells initiate their differentiation, the smooth endoplasmic reticulum and the Golgi apparatus become prominent and the first small lipid droplets appear in the cytoplasm. When fractured through a plane close to their surface, lipid droplets appear onion-like structured, ie made up of a variable number of irregular shaped concentric lamellae. This lamellar organization suggests that membranes are not only involved in synthesis, but also that some of their components are incorporated in the fat droplets. The authors conclude that human meibomian glands are a holocrine glandular complex that, despite great differences in type and location, present basic similarities with sebaceous glands.

Polychlorinated biphenyls poisoning in monkey eye.

Poisoning by polychlorinated biphenyl(s) (PCB) in humans leads to cutaneous and ocular findings. A white, cheeselike secretion issuing from the orifice of the Meibomian gland duct when the eyelid is squeezed is one sign of this intoxiation. In the rhesus monkey, abnormal hyperkeratosis of the ductal epithelium was observed histopathologically.

Meibomian gland studies: histologic and ultrastructural investigations.

Heightened interest in meibomian gland dysfunction has prompted us to evaluate the normal morphological and ultrastructural characteristics of the meibomian gland. Histologic analysis of human, primate, steer, and rabbit glands revealed evidence of keratinized epithelium extending throughout the meibomian gland duct. Characteristic ultrastructural features of keratinized epithelium identified in primate and rabbit glands included tonofilaments, keratohyaline granules, lamellar bodies, and keratinized squamous cells. Comparison of the meibomian gland duct to the pilosebaceous canal and the sebaceous duct brought out certain dissimilarities such as (1) the lack of a well-developed stratum granulosum and (2) the absence of lipid inclusions within transitional cells from duct to acini. We postulate that abnormalities of the keratinizing process may be responsible for meibomian gland dysfunction states.

Characterization of Meibomian gland innervation in the cynomolgus monkey (Macaca fascicularis).

To characterize the innervation of the cynomolgus monkey (Macaca fascicularis) Meibomian (tarsal) glands, upper lids of six cynomolgus monkeys were investigated with electronmicroscopical and double-labeling immunocytochemical methods. Antibodies against calcitonin gene-related peptide (CGRP), dopamine-beta-hydroxylase (DBH), neuropeptide Y (NPY), nitric oxide synthase (NOS), protein gene product 9.5 (PGP 9.5), substance P (SP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) were used. In addition, sections were processed for NADPH-diaphorase (NADPH-d) histochemistry. Staining for PGP 9.5 and electron microscopy showed that Meibomian gland acini were surrounded by a network of unmyelinated nerves and terminal varicose axons. The terminals contained small agranular (30-60 nm) and large granular vesicles (65-110 nm), and were observed in close contact with the basal lamina of the acini, but never internally to the basal lamina. Meibomian axons showed like-immunoreactivity (LI) for the neuropeptides SP, CGRP, NPY, and VIP. In addition, the axons stained for TH, DBH, NOS, and NADPH-d. VIP-LI, NOS- and NADPH-d-positive axons appeared to be more numerous, TH- and DBH-positive axons more rare than others. Most SP-LI axons were double-labelled for CGRP-LI, some for VIP-LI or NPY-LI. In addition, some VIP-LI axons were double-labeled for NPY-LI. NPY/VIP-LI and NPY/SP-LI axons were only observed close to the Meibomian acini. Conversely, NPY-LI colocalized with TH-IR or DBH-IR predominated in perivascular nerves of Meibomian gland vasculature. The close association of varicose axons with the acini of Meibomian glands indicates that nervous signals modulate meibomian secretion. Meibomian gland nerve fibers in the cynomolgus monkey appear to utilize various neuropeptides, catecholamines and nitric oxide as transmitter substances, and seem to derive from the pterygopalatine, superior cervical and trigeminal ganglion respectively.

[A case of Torre's syndrome: association of a meibomian adenocarcinoma with a cecal tumor]. / A propos d'un cas de syndrome de Torre: association d'un adénocarcinome meibomien et d'une tumeur caecale.

The authors report a case of sebaceous adenocarcinoma of the eyelid developed in meibomian glands. This tumor grew slowly for several years and was diagnosed three years after an intestinal adenocarcinoma was discovered in the same patient. This case is part of a Torre's syndrome (association of a sebaceous neoplasm and a visceral malignancy). Such an association represents an original example of multiple tumors and shows that the discovery of a sebaceous tumor, benign or malignant, indicates a careful search of an internal malignancy.

Antimicrobial role of human meibomian lipids at the ocular surface.

PURPOSE: Human meibomian lipids form the outermost lipid layer of the tear film and serve many important functions to maintain its integrity. Although not investigated earlier, these lipids may have antimicrobial properties that help in strengthening the innate host defense of tears at the ocular surface. The aim of this study was to investigate the antimicrobial role of human meibomian lipids. METHODS: Ocular pathogenic bacteria, Staphylococcus aureus 31, Pseudomonas aeruginosa 19, Pseudomonas aeruginosa 20, and Serratia marcescens 35, were grown in the presence and absence of human meibomian lipids in an artificial tear solution at the physiological temperature. Viable counts were obtained to note the number of bacteria surviving the treatment with meibomian lipids. Bacterial cells were imaged using scanning electron microscopy to observe the damages caused by meibomian lipids. RESULTS: Viable count results showed that in the presence of meibomian lipids, growth of all bacteria was considerably lower. Scanning electron microscopy showed that meibomian lipids caused extensive cellular damage to bacteria as manifested in smaller size, loss of aggregation, abnormal phenotype, cellular distortion, damaged cell wall, and cell lysis. CONCLUSIONS: This is the first-ever report of the antimicrobial role of human meibomian lipids. These lipids possess antimicrobial properties against both Gram-positive and Gram-negative bacteria and are involved in the innate host defense of tears in protecting the ocular surface against microbial pathogens.

Ultrastructure of the sexually dimorphic tarsal glands and tegumental glands in gonyleptoid harvestmen (Opiliones, Laniatores).

In at least four closely related families of the diverse harvestmen lineage Gonyleptoidea, males may possess sexually dimorphic tarsal glands in the swollen tarsomeres of the basitarsus and/or metatarsus of leg I. The first histological and ultrastructural examination of the sexually dimorphic tarsal glands in leg I focused only on Manaosbiidae. In this study, we examine the morphology and ultrastructure of the sexually dimorphic glands, and their associated glandular openings, found in the basitarsus and/or metatarsus of leg I of males representing Cosmetidae, Gonyleptidae, and Cranaidae (glandular openings only). In cosmetids and gonyleptids, the tarsal glands are made up of 20­60 glandular units that form distinct groups within the prolateral and retrolateral half of the tarsomere. Each glandular unit consists of a pair of terminal secretory cells, an intercalary cell wrapped around the receiving canal, and a canal cell tightly wrapped around the length of the conducting canal. Cosmetidae, Gonyleptidae, and Cranaidae exhibit remarkably similar tarsal glands and gland openings although the location of the glands in the leg differs slightly among them. Males of these three families exhibit markedly different glands and glandular openings compared to males of the family Manaosbiidae. The sexually dimorphic tarsal glands may provide an important morphological character for determining phylogenetic relationships among gonyleptoid families. Finally, we provide morphological and ultrastructural data for the common tegumental glands. These data indicate that the sexually dimorphic tarsal glands are strikingly similar to, and may possibly be derived from, the tegumental glands.

Characterization of the mucocutaneous junction of the human eyelid margin and meibomian glands with different biomarkers.

PURPOSE: To investigate the morphology of the human eyelid margin and the presence of different cytokeratins, mucins and stem cell markers within the skin epithelium, mucocutaneous junction (MCJ) and palpebral conjunctiva. METHODS: Eyelids of body donors were investigated histologically and ultrastructurally as well as by immunohistochemical methods using antibodies to cytokeratins 1, 4, 7, 8, 10, 13, 14, 15, and 19; mucins MUC1, MUC4, and MUC5AC and potential stem cell markers K15, BCRP/ABCG2, integrin ß1, and N-cadherin. RESULTS: The expression pattern of cytokeratins, mucins and stem cell markers varied across the different epithelia of the human eyelid. Within the MCJ, CK7, 15 and 19 were absent, whereas the epithelium reacted positive to antibodies to CK1, 4, 8, 10, 13 and 14. Reactivity was also observed for MUC1 and MUC4, but not for MUC5AC. No reactivity was determined for K15, BCRP/ABCG2 and integrin ß1 in the area of the MCJ epithelium but a strong reactivity was present for N-cadherin. CONCLUSIONS: The present immunohistochemical findings lead to a better characterization of the MCJ. Additionally, the knowledge of distribution of biomarkers like cytokeratins, mucins and stem cells can be useful in the investigation of MCJ disturbances which occur in several disorders of the meibomian glands and the lid epithelium in the course of dry eye syndrome and especially meibomian gland dysfunction.

Lipidomics of human Meibomian gland secretions: Chemistry, biophysics, and physiological role of Meibomian lipids.

Human Meibomian gland secretions (MGS) are a complex mixture of diverse lipids that are produced by Meibomian glands that are located in the upper and the lower eyelids. During blinking, MGS are excreted onto the ocular surface, spread and mix with aqueous tears that are produced by lachrymal glands, and form an outermost part of an ocular structure called "the tear film" (TF). The main physiological role of TF is to protect delicate ocular structures (such as cornea and conjunctiva) from desiccating. Lipids that are produced by Meibomian glands are believed to "seal" the aqueous portion of TF by creating a hydrophobic barrier and, thus, retard evaporation of water from the ocular surface, which enhances the protective properties of TF. As lipids of MGS are interacting with underlying aqueous sublayer of TF, the chemical composition of MGS is critical for maintaining the overall stability of TF. There is a consensus that a small, but important part of Meibomian lipids, namely polar, or amphiphilic lipids, is of especial importance as it forms an intermediate layer between the aqueous layer of TF and its upper (and much thicker) lipid layer formed mostly of very nonpolar lipids, such as wax esters and cholesteryl esters. The purpose of this review is to summarize the current knowledge on the lipidomics of human MGS, including the discussions of the most effective modern analytical techniques, chemical composition of MGS, biophysical properties of Meibomian lipid films, and their relevance for the physiology of TF. Previously published results obtained in numerous laboratories, as well as novel data generated in the author's laboratory, are discussed. It is concluded that despite a substantial progress in the area of Meibomian glands lipidomics, there are large areas of uncertainty that need to be addressed in future experiments.

Virus-induced chalazion.

PURPOSE: To investigate a viral etiology in certain chalazia. METHODS: A prospective study over 7.5 years of all newly presenting chalazia associated with diffuse follicular conjunctivitis but without any other aetiological factors. Patients were investigated for ocular or systemic infections by history, physical exam, slit-lamp exam, and/or histology of conjunctival biopsy (including transmission electron microscopy). RESULTS: A total of 27 patients developed follicular conjunctivitis without meibomian gland dysfunction, blepharitis, or sexually transmitted diseases. Evidence for a viral aetiology included: recent systemic viral illness (15/27), recent contact with subjects with chalazia or follicular conjunctivitis (5/27), preauricular lymphadenopathy (4/27), viral corneal disease (4/27), or viral particles by ultrastructure (4/4). CONCLUSIONS: Chalazia may be associated with viral conjunctivitis. Intralesional corticosteroids should be considered with great caution for viral-induced chalazia.

Peroxisomes in sebaceous glands. IV. Aggregates of tubular peroxisomes in the mouse Meibomian gland.

The occurrence of peroxisomes, their morphogenesis during the process of sebaceous transformation and their spatial relationship to the endoplasmic reticulum and lipid droplets were investigated by light and electron microscopy after visualization of the peroxidatic activity of catalase using an alkaline diaminobenzidine medium. The morphological alterations of peroxisomes display a characteristic sequence: During cellular differentiation, a remarkable proliferation of exclusively tubular, diaminobenzidine-reactive peroxisomes occurs. As maturation proceeds, an extensive elongation of tubular peroxisomes is seen. Concomitantly, they are densely packed in a regular, hexagonal arrangement and both the diameter and the catalase content gradually decreases. The most conspicuous feature of mature glandular cells are numerous highly organized aggregates of tubular, almost unstained peroxisomes with a diameter of 50 nm, arranged in a hexagonal pattern. They resemble adjacent tubular profiles of smooth endoplasmic reticulum. However, membrane continuities between these two compartments were never observed. During lethal disintegration peroxisomes subsequently decrease in number, probably by rapid sequestration within autophagolysosomes. The role of tubular peroxisomes in the biosynthesis of wax esters in the mouse Meibomian gland is discussed.

Immunocytochemical and ultrastructural evaluation of the distribution of nervous tissue and neuropeptides in the meibomian gland.

BACKGROUND: The ultrastructure of the meibomian gland, of its innervation and the localization of neuropeptides in the glandular tissue of the guinea pig and humans are incompletely known. Therefore they have been investigated in the present study. METHODS: The ultrastructure of the tissue was examined using standard transmission electron microscopic techniques. Additional scanning electron microscopy was carried out on rabbit tissue. Antisera against the neuronal marker protein gene product were used to demonstrate the distribution pattern of the nerve fibers. The neuropeptides substance P (SP) and neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) and the neuronal enzyme tyrosine hydroxylase (TH) were identified by their specific antisera. RESULTS: The glands were found to be composed of arrays of alveoli. The outer cells of the alveoli form a germinal layer. Toward the inside of the alveolus the cells are laden with a secretory substance. The cells disintegrate as they approach the excretory duct. Nerve fibers form a plexus around the alveoli. These nerve fibers form synapses à distance to the basal alveolar cells and enter the basal lamina of the capillaries. In guinea pigs many nerve fibers were positive for the neuropeptides SP and NPY and for VIP, and fewer for CGRP and TH; in humans only SP and CGRP were demonstrated. CONCLUSION: Both the density of nerve fibers and the presence of various neuropeptides suggest that the stimulation of the meibomian gland is subject to nervous control.