Accessory Lacrimal Glands Research Articles

Adenoid cystic carcinoma of the superonasal conjunctival fornix

The case of a 32-year-old female with a mass in the superonasal conjunctival fornix is described. Histological examination revealed an adenoid cystic carcinoma, which we consider to be most likely derived from an accessory lacrimal gland. The clinical presentation, histological features, management and follow-up are described. A literature review of orbital adenoid cystic carcinoma arising outside the main lacrimal gland is presented.

Characterization of adrenergic receptors in the accessory lacrimal glands of the upper eyelid.

To identify the histologic location as well as the exact subtype of adrenergic receptors in the accessory lacrimal glands of the upper eyelid. Upper eyelid specimens were collected from 19 patients undergoing routine blepharoptosis correction via a posterior tarsoconjunctival mullerectomy. Immunohistochemical staining using polyclonal antibodies against human alpha 1, alpha 2, beta 1, and beta 2 receptors was performed on all specimens. beta 1 receptors were the predominant adrenergic receptor subtype in the glands of Wolfring. The presence of beta 1 receptors in the accessory lacrimal glands of the upper eyelid may suggest a possible role for selective beta 1 agonists in the treatment of keratitis sicca.

Vasoactive Intestinal Polypeptide (VIP) Innervation of the Human Eyelid Glands

This study was conducted to obtain morphological proof of innervating nerve fibres in the glands of the human eyelid (accessory lacrimal glands of Wolfring, meibomian glands, goblet cells, glands of Zeis, glands of Moll, sweat glands, glands of lanugo hair follicles) and identification of the secretomotorically active neuropeptide vasoactive intestinal polypeptide (VIP) as a common transmitter. Epoxy-embedded ultrathin sections of tissue samples from human eyelids were studied using electron microscopy. Paraffin sections fixed in Bouin–Hollande solution were immunostained with rabbit antiserum against VIP. With the electron microscope we were able to identify nerves in the glandular stroma of all the glands examined with the exception of goblet cells. Intraepithelial single axons were only seen in the parenchyma of Wolfring glands. The morphological findings corresponded with the immunological finding of VIP-positive, nerve-like structures in the same locations, with the exception of lanugo hair follicle glands, and goblet cells. Our findings indicate that the glands of the eyelids and main lacrimal gland represent a functional unit with VIP as a possible common stimulating factor.

The Acinar and Ductal Organisation of the Tarsal Accessory Lacrimal Gland of Wolfring in Rabbit Eyelid

The purpose of this study was to objectively assess the tarsal accessory lacrimal gland of Wolfring and its excretory duct by transmission electron microscopy (TEM). The upper eyelid of 6 female grey rabbits (2 kg) was fixed in the fully extended configuration with buffered glutaraldehyde. At the tarsal/orbital portion of the palpebral conjunctiva, a series of prominent acinar glands were located by both light microscopy and TEM. Cells within the acini were characterised by apical tight junctions and desmosomal connections as well as abundant intra-cytoplasmic osmophillic (secretory) granules. The apical surfaces were profusely decorated with microvilli-like extensions. In the vicinity of the acini, and traversing over several millimetres of adjacent sub-epithelial parenchyma and epithelium, was an extensive system of duct-like spaces lined with secretory cells decorated with microvilli. These ducts run a tortuous course within the palpebral conjunctival epithelium leading to crypt-like termination's along the eyelid inner surface. The tarsal accessory lacrimal gland of Wolfring thus has an acinar structure similar to the main lacrimal glands, and its ducts are lined by secretory cells along the entire tortuous course towards the palpebral conjunctival surface, where the ducts emerge at multiple points at the tarsal/orbital portion of the surface.

An immunohistochemical study of collagens in trachoma and vernal keratoconjunctivitis.

To analyse the distribution and types of collagen in the conjunctiva of patients with trachoma and vernal keratoconjunctivitis (VKC). Conjunctival biopsy specimens were collected from 9 patients with active trachoma, 9 patients with scarred trachoma, 6 patients with active VKC and 9 control subjects. The presence and distribution of collagen was assessed microscopically with immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against types I, III, IV and V collagen. In normal conjunctiva, the staining for types I and III collagen was localised to the substantia propria. Type IV collagen was located in the epithelial, vascular endothelial and accessory lacrimal gland basement membranes. Staining for type V collagen was absent. New type V collagen deposition close to basement membranes was noted in active trachoma, scarred trachoma and VKC. The extent of deposition of type V collagen was markedly increased in scarred trachoma when compared with active trachoma. Staining for type IV collagen showed irregularly thickened epithelial basement membrane in active trachoma, and a marked increase in basement membrane type IV collagen was noted in scarred trachoma. Immunoreactivity of types I and III collagen increased in active trachoma and decreased in scarred trachoma. VKC conjunctiva contained increased amounts of types I, III and IV collagen due to marked increase in the thickness of vascular endothelial basement membrane and very prominent deposition of types I and III collagen around stromal vessels. Our data indicate new type V collagen formation in the conjunctiva from patients with active trachoma, scarred trachoma and VKC. Increased deposition of types I, III and IV collagen is noted in VKC and active trachoma. Our findings suggest that increased deposition of type IV collagen and new type V collagen formation contributes to the development of conjunctival fibrosis in scarred trachoma.

Small-volume analysis of rabbit tears and effects of a corneal wound on tear protein spectra.

Tears are a complex fluid composed of secretory products from several sources, such as the orbital lacrimal gland, accessory lacrimal glands, goblet cells, meibomian glands, and perhaps other cells of the conjunctiva and cornea. Previous studies have shown that the lacrimal fluid contains growth factors, as well as a number of other proteins, that may act to protect the ocular surface.1–3 A compilation of known tear proteins of laboratory animals is shown in Table 1.4–23

Video biomicroscopy of the tear film.

The tear film is produced by the lacrimal gland, the accessory lacrimal glands, and the goblet cells of the conjunctiva, with the meibomian glands of the eyelids providing an oily surface layer. The tear film covers the eye and is drained from the surface via two puncta that lead through the canaliculi to the lacrimal sac, which is in the lacrimal fossa. From here, the tears flow in a duct in the bony nasolacrimal canal to the inferior nasal meatus.

Malignant Melanoma of the Lacrimal Sac Complicating Primary Acquired Melanosis of the Conjunctiva

An 81-year-old woman with primary acquired melanosis of the conjunctiva had multinodular invasive malignant melanoma, with one nodule engulfing the superior lacrimal punctum. At exenteration, the lacrimal sac was noted to be involved with melanoma, and an en bloc resection of the orbital contents along with the medial orbital wall and the medial wall of the maxillary antrum was performed to excise the lacrimal drainage apparatus. In situ melanoma was found in the superior canaliculus with invasive melanoma in the lacrimal sac. In situ melanoma was also found in the ductules of the lacrimal gland and the accessory lacrimal glands of the fornix. The patient died 8 months later of metastatic melanoma. The involvement of the lacrimal drainage apparatus by primary acquired melanosis or in situ melanoma makes clinical monitoring and management difficult.

Clinical aspects and histopathology of caruncular tumors

Histologically the lacrimal caruncle represents a transition zone between the conjunctiva and the skin containing cutaneous, conjunctival and lacrimal elements. This accounts for a variety of histopathological changes. We conducted a retrospective study on the histopathological findings of 65 caruncular lesions which were referred for excisional biopsy between 1974 and 1995 to the Department of Ophthalmology at the University of Heidelberg. The age of the patients ranged from 10-87 years (mean 42 +/- 18.2). Histopathologic diagnoses included 29 (45%) nevi, 15 (23%) papillomas, 7 (11%) chronic inflammatory lesions and 4 (6%) epidermoid cysts. In addition, 4 (6%) semimalignant and malignant tumours were found including one basalioma, one squamous cell carcinoma and two Kaposi-sarcomas. Among the remaining 8% a dermoid cyst, an accessory lacrimal gland with a retention cyst, an epithelial implantation cyst, a teleangiectatic granuloma and an oncocytoma were diagnosed. These findings suggest that malignant caruncular lesions are rare, however excisional biopsy appears prudent in order to establish the histological diagnosis.

Ostensible oncocytoma of accessory lacrimal glands

Benign oncocytomas of the accessory lacrimal glands can be found in the lacrimal caruncle, plica semilunaris or conjunctival fornices, but are extremely rare. A series of 15 supposed oncocytomas of the ocular adnexa was reviewed retrospectively, and histological differences were noted with respect to the parotid gland counterpart. Lesions could be divided into three histological groups: (1) tumours composed of tubules lined by tall columnar epithelium with finely granular cytoplasm; the tubules often had dilated lumens containing mucinous secretion; (2) cystic tumours with prominent epithelial tufts projecting from much of the cyst wall; (3) tumours with solid areas composed of variably cuboidal or polygonal cells, largely in trabecular arrangement, and co-existing with the previously described tubular and cystic elements. A striking resemblance to Warthin's tumour without a lymphocytic component, such as may affect the parotid salivary gland, was noted in several tumours.

Distribution pattern of nervous tissue and peptidergic nerve fibers in accessory lacrimal glands

PURPOSE. Demonstration of the distribution pattern of nervous tissue and the occurrence of neuropept human accessory lacrimal glands by means of immunohistochemical methods. METHODS. Paraffin sections of tissue samples were incubated with antisera against protein gene product (PGP), S-100 protein (S-100), calcitonin gene-related peptide (CGRP) and substance P (SP). The immunoreactions were visualized using both species-specific secondary antibodies and a streptavidin-biotin-peroxidase complex (ABC method). RESULTS. PGP- and S-100-immunoreactive nerve fibers were distributed in the entire intertubular stroma. In addition, myoepithelial cells, a few clusters of tubulus cells, groups of wandering cells, and scattered cells of the excretory duct system were S-100-immunoreactive. CGRP- and SP-immunoreactivity was found in a few nerve fibers in the intertubular glandular stroma with an association to secretory tubules, blood vessels, intralobular ducts and excretory duct. CONCLUSIONS. These observations are in agreement with findings in the main lacrimal gland.

Organ Culture of Human Main and Accessory Lacrimal Glands and their Secretory Behaviour

The purpose of this study was to investigate the in vitro viability and secretory behaviour of human main and accessory lacrimal glands using an organ culture technique. We evaluated the influence of the second messengers cAMP and cGMP on secretion. Fragments less than 1mm 3of main and accessory lacrimal glands as well as conjunctiva were cultured for 2–72hr at 37°C in an atmosphere consisting of 50% O 2, 45% N 2and 5% CO 2, using a specially devised culture medium (±cAMP or cGMP). The conjunctival tissue served as negative control. Supernatants were assayed for secretory-component-bound IgA, lactoferrin and lysozyme using ELISA. Cultured tissue pieces were embedded in paraffin, serially sectioned, stained and their volumes calculated using an image-analysis system. This enabled us to differentiate between secretory, connective and fatty tissue. Secreted exudate was correlated to the volume of secretory tissue. Viability of cultured organ pieces was determined by electron microscopic examination. Suitable organ culture conditions for human lacrimal glands were successfully established. Electron microscopic examinations proved that the structural characteristics of the organ and the polarity of the individual cells were well preserved up to 22 days of culture. Culture supernatants were assayed for secretory-component-bound IgA, lactoferrin, and lysozyme and showed that the amount of protein secreted increased with time. Upon addition of cAMP (1×10 -3 m) and cGMP (4×10 -3 m), secretion was elevated in both main and accessory lacrimal glands. An organ culture system for lacrimal glands was developed that maintains their structural and cellular characteristics as well as their secretory function for up to 22 days. We believe that this system mimics the in vitro state of the organ better than monolayer cultures and thus proves to be a valuable tool when examining lacrimal function in vitro. The fact that both cAMP and cGMP enhance secretion may help to shed some light on the cellular pathways human main and accessory lacrimal glands use for signal transduction.

Demonstration of nerve fibers in human accessory lacrimal glands.

To provide morphologic evidence for the innervation of accessory lacrimal glands, glands were biopsied and examined using standard transmission electron microscopic techniques. Non-myelinated nerve fibers were found in the connective tissue between the glandular epithelia where they made contact with glandular epithelial cells, myoepithelial cells, vascular endothelial cells, plasma cells and fibroblasts. The distances measured between axons and target cells ranged from 30 to 130 nm. Where nerve fibers approached cells sustaining a basement membrane, their basement membranes fused to form a discrete unit resembling so-called 'synapses à distance'. Cells with no basement membrane were situated in direct contact with the basement membrane of a nerve fiber. Single axons were identified between glandular epithelial cells and cells of intralobular ducts. Most of these axons contained many small clear vesicles and a few large, dense core vesicles, a finding considered typical of cholinergic parasympathetic nerve fibers. In addition, one of the axons identified contained small dense core vesicles typical of sympathetic nerve fibers. Human accessory lacrimal glands are therefore definitely innervated, with parasympathetic structures morphologically prevailing over sympathetic structures.

Galactose- binding sites in the acinar cells of the human accessory lacrimal gland.

This investigation for the first time has collected evidence of a specific glycoconjugate contribution of the acinar cells from accessory lacrimal glands to human tears. Amongst group III lectin binding glycoconjugates, monosaccharides seem to be more prominent than disaccharides. alpha (and less obvious beta) Galactose sugar moieties appear to be specifically important. A need for further differentiating investigations is outlined.

Wolfring Dacryops

A unique series of 13 cases of ductal cysts of the accessory lacrimal glands of Wolfring is presented. Once appreciated, they are an easily recognized clinical entity. The 13 cases were verified histologically as arising from ductal epithelium. Biochemical analyses for serum and cyst fluid concentrations of IgA, IgG, and IgM were performed on three of the cases. Histologic staining of the cyst wall using monoclonal antibodies to immunoglobulins was performed on one case. All patients had evidence of extensive trachomatous scarring. High levels of IgA were found in the cyst fluid, consistent with an active secretory mechanism. Monoclonal antibody staining suggested a significant role for paraductal IgA-secreting plasma cells. The formation of a ductal cyst appears to require two successive, inter-related events. The first is an ongoing active secretory process, and the second is an occlusion of the duct. The sequential occurrence of these two events is forwarded as the explanation of dacryops formation. Excision using a conjunctival approach is recommended. A small strip of tarsal border should be removed with the cyst to prevent cyst rupture. The excretory ducts of the Wolfring glands exit through this area.

Antigenic profile of the human lacrimal gland.

The antigenic profile of 13 normal formalin-fixed, paraffin-embedded human main and accessory lacrimal glands, biopsied from patients aged 11 to 78 years, was studied using a panel of 27 polyclonal and monoclonal antibodies. Secretory cells of lacrimal acini reacted with antibodies to S-100 protein and simple epithelium-type cytokeratins CK 7, CK 8, CK 18, and CK 19. Their luminal membranes were labeled with antibodies to carcinoembryonic antigen, epithelial membrane antigen, and epithelial glycoproteins recognized by Ber-EP4. Myoepithelial cells were often immunopositive for S-100 protein, vimentin, glial fibrillary acidic protein (GFAP), and alpha-smooth muscle actin. More rarely, they reacted with antibodies recognizing CK 5, CK 13, and CK 14, which consistently labeled the basal cells of lacrimal ducts. Unlike myoepithelial cells, basal ductal cells were immunopositive for CK 7, CK 8, CK 18, and CK 19. In main excretory ducts, dendritic melanocyte-like cells co-expressing vimentin and S-100 protein intermingled with ductal epithelial cells. The luminal cells of lacrimal ducts basically paralleled secretory cells in their antigenic profile, although they lacked Ber-EP4 and were immunopositive for CK 4. Antibodies to neuron-specific enolase and synaptophysin reacted with nerve fibers among negatively reacting secretory acini. This antigenic profile closely parallels that of salivary glands and provides a basis for studies of lacrimal gland pathology.

ACCESSORY LACRIMAL GLANDS

ACCESSORY LACRIMAL GLANDS

Immunohistochemical characterization of epithelial cells in human lacrimal glands

Expression patterns of cytokeratins (CKs), actin, lactoferrin (Lf), lysozyme (Ly), vimentin, and S-100 protein were immunohistochemically examined in paraffin sections from eight normal major and accessory lacrimal glands (LGs). Luminal duct cells and a number of secretory cells stained with the antibodies (ABs) KL1 and Pkk1 (CK 7, 8, 17, 18), while basal duct and myoepithelial cells reacted with the AB 34 beta E12 (CK 5). Myoepithelial cells expressing CK 5 and actin were restricted to acini and intralobular ducts, and their number was greater in major LGs than accessory ones. Lf and Ly were found in 50%-75% of acini and intralobular ducts. Vimentin was absent in parenchyma of LGs. S-100 protein reaction was observed in a number of acinar and luminal duct cells of major LGs whereas epithelia of accessory LGs remained negative. Distribution patterns of CKs, Lf, and Ly in major and accessory LGs are identical. The difference with respect to the number of myoepithelial cells as well as S-100 protein reactivity between major and accessory LGs reactivity appeared to be relevant to the differences in their secretory mechanisms and local environment.

Eledoisin and lacrimal secretion in the rabbit

Eledoisin has been tried as a possible treatment for dry eye based on the hypothesis that it pharmacologically stimulates tear secretion when topically applied to the eye. To determine if topically applied eledoisin pharmacologically stimulates orbital lacrimal secretion, the orbital lacrimal gland excretory duct of normal rabbits was cannulated, and eledoisin was applied topically with and without prior administration of proparacaine. To determine if topically applied eledoisin stimulated accessory lacrimal gland secretion, isotonic buffer with and without eledoisin was tested in a rabbit model with only accessory lacrimal tissue remaining after the administration of proparacaine. Topically applied eledoisin did not pharmacologically stimulate lacrimal secretion but rather increased lacrimal gland secretion only in non-anesthetized eyes through a sensory reflex mechanism that is blocked by proparacaine.

Immunopathology of trachomatous conjunctivitis.

Upper palpebral conjunctival biopsy specimens obtained from eight patients with active trachoma were examined by routine histological and immunohistochemical methods. The epithelium expressed class I major histocompatibility complex (MHC) products throughout and class II MHC products in the superficial layers. The epithelial inflammatory infiltrate consisted of polymorphonuclear leucocytes, macrophages, T lymphocytes, and dendritic cells. In the underlying stroma the inflammatory infiltrate was organised as B lymphoid follicles, and there was also a diffuse infiltrate consisting of plasma cells and scattered B lymphoid cells, dendritic cells, T cells, macrophages, and polymorphonuclear leucocytes. Each type of cell has its special location in the tissue. Plasma cells were located on a subepithelial band and as a dense infiltrate round the acini of accessory lacrimal glands. IgA+ plasma cells outnumbered IgG+ cells, whereas IgM+ and IgE+ cells were few. Our data provide good evidence for the presence of both humoral and cell mediated immune responses and a possible role for autoimmune mechanisms in the conjunctival tissues of trachoma patients.