Andreas B. Thale

New insights into the pathophysiology of primary acquired dacryostenosis

OBJECTIVE To obtain new insights into the pathophysiology of primary acquired dacryostenosis. DESIGN Comparative autopsy tissue study with histopathologic correlations. MATERIALS Tissue specimens from the human nasolacrimal ducts of 36 patients undergoing endonasal dacryocystorhinostomy within a framework of primary acquired dacryostenosis were analyzed by histologic studies and electron microscopic examination. Six lacrimal systems of body donors served as controls. TESTING One group of tissue specimens from each lacrimal system was prepared and processed with paraffin, sectioned, stained by different methods, and finally examined by light microscopy. The other group was processed with araldite after preparation, sectioned semithin and ultrathin, and examined by transmission electron microscopy. MAIN OUTCOME MEASURES The degree of dacryostenosis was scored in each tissue specimen by grading the histologic sections as mild (active chronic inflammation), moderate (proliferative sclerotic forms of chronic fibrosis), or severe (total subepithelial fibrosis). RESULTS Of 36 patients with epiphora, 13 had functional obstruction with a patent lacrimal system on syringing; in 23 cases, the lacrimal passage was completely obstructed. Different pathologic stages correlating to duration of symptoms were found ranging from active chronic inflammation to proliferative sclerotic forms and total subepithelial fibrosis. CONCLUSIONS Descending inflammation from the eye or ascending inflammation from the nose initiates swelling of the mucous membrane, remodeling of the helical arrangement of connective tissue fibers, malfunctions in the subepithelial cavernous body with reactive hyperemia, and temporary occlusion of the lacrimal passage. In the follow-up, repeated isolated occurrence of dacryocystitis leads to structural epithelial and subepithelial changes, which may lead either to a total fibrous closure of the lumen of the efferent tear duct or to a nonfunctional segment in the lacrimal passage that is manifest on syringing.

Functional anatomy of human lacrimal duct epithelium.

Abstract Resorption of tear fluid in the lacrimal ducts has hitherto been controversial; one reason for this has been insufficient knowledge of the anatomical structure and function of the lacrimal duct epithelium. The present study analyzes the structure of lacrimal duct epithelium by means of histological, histochemical, immunohistochemical and electronmicroscopical methods and draws a conclusion about its physiological function regarding its role in immunodeficiency. Investigations were performed on 31 lacrimal systems of 17 male and 14 female individuals (aged 54–88 years). Lacrimal ducts are surrounded by a wide-ranging cavernous system, which is embedded in an osseous canal between the maxilla and the lacrimal bone. The internal wall of the lacrimal canaliculi is lined by a stratified epithelium. The lacrimal sac and nasolacrimal duct contain a double-layered epithelium, which rests on a broad basement membrane. In their apical part epithelial cells contain large lipid droplets and secretory vacuoles. Epithelial cells are faced by microvilli and some tufts of kinociliae are also visible. Goblet cells are integrated in the epithelium as solitary cells or in a characteristical arrangement of several cells. The secretory product of these cells contains carbohydrates including fucose and sialic acid. Inside the surrounding cavernous system serous glands are found that open their excretory ducts into the lacrimal sac and nasolacrimal duct. Some T- and B-lymphocytes and macrophages may be demonstrated immunohistochemically in the submucosa partly penetrating the epithelium. Synthesized mucins of goblet cells form a specialized protective layer on the epithelium of the lacrimal ducts, which functionally serves for a simplified drainage of tear fluid into the inferior meatus of the nose. Together with immunocompetent cells, the protective layer plays a role in antigen defense and prevents invasion of pathogenic agents. The facing of epithelial cells by microvilli gives hints of reabsorption of lacrimal fluid inside the lacrimal ducts.

Functional anatomy of the human efferent tear ducts: a new theory of tear outflow mechanism

Abstract · Background: The mechanism of lacrimal drainage under physiological conditions is controversial. The aim of this study was to analyze the three-dimensional architecture of human efferent tear ducts from functional and clinical points of view. A new theory of tear outflow is discussed. · Methods: Thirty-two prepared lacrimal systems of adults were examined by histological, immunohistochemical and scanning electron microscopic techniques. · Results: The wall of the lacrimal sac is made up of collagen bundles, elastic and reticular fibers arranged in a helical pattern. Wide luminal vascular plexus are embedded in this helical system and connected to the cavernous tissue of the inferior turbinate in the region of Hasner’s valve. Immunohistochemical analysis showed evidence of type I and type III collagen as well as chondroitin 4- and 6-sulfate. · Conclusion: With blinking, the lacrimal part of the orbicularis muscle contracts. The fornix of the sac moves in a cranial-lateral direction. Thus the lacrimal sac distends and may be ’’wrung out’’ due to its medial attachment and helically arranged fibrillar structures. The vascular plexus may play an important role in the absorption and drainage of lacrimal fluid.

Drainage of Tears: Impact on the Ocular Surface and Lacrimal System

The human efferent tear ducts are part of the lacrimal system. Because little knowledge exists concerning the physiology of the nasolacrimal system, and hence its patho- physiology, the nasolacrimal system has received almost no consideration as a possible factor in dry eye. The human nasolacrimal ducts consist of the upper and the lower lacrimal canaliculus, the lacrimal sac, and the nasolacrimal duct. As a draining and secretory system, the efferent tear ducts play a role in tear transport and nonspecific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a surrounding vascular system. This system is similar to a cavernous body that is subject to autonomic control and regulates tear outflow. Tear duct-associated lymphoid tissue (TALT) is present in the efferent tear ducts, displaying the cytomorphological and immunophenotypic features of mucosa-associated lymphoid tissue (MALT). Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production, which ceases if these tear components are not absorbed. In this way, dry eye could be initiated. Defective stimulation of TALT could result in abnormal immune deviation at the ocular surface, leading to an autoimmunological response that causes dry eye pathology.

Mucosa-associated lymphoid tissue in human efferent tear ducts

Abstract The recent description of primary marginal zone lymphomas in human efferent tear ducts with typical features of lymphomas arising in mucosa-associated lymphoid tissue (MALT) infers the presence of MALT in the human efferent tear ducts. To date, studies have not established clearly whether organised MALT occurs in normal human efferent tear ducts. To elucidate this problem, efferent lacrimal pathways from unselected body donors with unknown prior history of efferent tear duct, ocular, or nasal disease were examined for the presence of organised MALT. Organised lymphoid tissue was found with the cytomorphological and immunophenotypic features of MALT in 41% of the cases examined. These findings suggest that MALT is a feature that, although it need not be present in normal efferent tear ducts, is acquired during life in a proportion of apparently asymptomatic individuals.

Innervation of the cavernous body of the human efferent tear ducts and function in tear outflow mechanism

The lacrimal sac and nasolacrimal duct are surrounded by a wide cavernous system of veins and arteries comparable to a cavernous body. The present study aimed to demonstrate the ultrastructure of the nervous tissue and the localisation of neuropeptides involved in the innervation of the cavernous body, a topic not previously investigated. Different S‐100 protein antisera, neuronal markers (neuron‐specific enolase, anti‐200 kDa neurofilament), neuropeptides (substance P, neuropeptide Y, calcitonin gene‐related peptide, vasoactive intestinal polypeptide) and the neuronal enzyme tyrosine hydroxylase were used to demonstrate the distribution pattern of the nervous tissue. The ultrastructure of the innervating nerve fibres was also examined by means of standard transmission electron microscopy.

Organized Mucosa-Associated Lymphoid Tissue in Human Nasolacrimal Ducts

We have recently established procedures for the isolation of highly purified lacrimal gland acinar cells (pLGAC) (Guo et al., 2000) and a culture method that promotes proliferation of the cells (Schonthal et al., 2000). Many studies have shown the benefits of seeding lacrimal cells onto Matrigel coated plates (Kelleher et al., 1991; Menerey et al., 1994; Millar, et al., 1996; Chen et al., 1998). Our procedure utilizes a method which coats the pLGAC with Matrigel to more closely mimic the in vivo condition where acinar cells are enveloped by matrix molecules on their basal surfaces. This has been achieved by trapping pLGAC in Matrigel rafts. These free-floating raft cultures have been maintained in vitro for up to 28 days for morphological and physiological studies.

The collagen architecture of the sciera — SEM and immunohistochemical studies

Summary The arrangement of the collagen fibrils of the sciera was analyzed at defined areas by using SEM with regard to morphological alterations in cases of glaucoma and to postoperative astigmatism after cataract operations. Adult eyes with no apparent pathological changes were studied. In the lamina cribrosa the collagen fibrils are arranged circularly around the points of passage of the axons and vessels. In the region of the muscle attachments the tendinous collagen fibrils intersect the bundles of collagen fibrils of the sciera at right angles. The collagen fibrils form a reticular structure on the external surface of the sciera. A main route of alignment can only be identified in a few places. The collagen fibrils are aligned in a rhombic pattern on the internal surface of the sciera. The immunohistochemical analysis revealed collagen types I and III in the sciera, while collagen types I, III and IV were found in the lamina cribrosa.

Epithelial-connective tissue boundary in the oral part of the human soft palate

The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3‐dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial‐connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates.

Protection of Human Efferent Tear Ducts by Antimicrobial Peptides

Pathogenic microorganisms usually interact with higher organisms at epithelial surfaces where they adhere, and, if they survive, either multiply locally or invade deeper tissues. Since pathogen-specific immune responses develop slowly, it is not surprising that epithelial cells are equipped with various antimicrobial substances that act rapidly to control the growth of a broad range of potentially pathogenic microorganisms on body surfaces. Some of these innate host defense molecules restrain microbes by depriving them of essential nutrients. Other antimicrobial peptides kill by disrupting pathogen cell structures.1