The cavernous body of the human efferent tear ducts contributes to regulation of tear outflow.

PURPOSE: To test the hypothesis that the surrounding vascular plexus of the lacrimal sac and the nasolacrimal duct contributes to the regulation of tear outflow. METHODS: Experiments in 30 probands aged between 15 and 37 years were performed in both nasolacrimal systems of each subject by observing with an endoscope the transit time of an applied tear drop containing fluorescein dye until its entry into the inferior meatus of the nose. Four different experiments were performed to determine the median transit time under normal conditions and the influence on transit time of a decongestant drug, a foreign body on the ocular surface, and a decongestant drug applied together with a foreign body on the ocular surface. Comparisons were made between the right and left nasolacrimal system, in males and females, eyeglass wearers and non-eyeglass wearers, and the different experiments and the results statistically analyzed. RESULTS: The tear transit time was independent of side (right or left), gender, or eyeglass wear. It showed great individual variability. Application of a decongestant drug or placement of a foreign body on the ocular surface both prolonged the dye transit time significantly. Application of a decongestant drug simultaneously with placement of a foreign body shortened the dye transit time significantly compared with the effect of the decongestant drug alone but revealed no significant difference compared with application of a foreign body alone. CONCLUSIONS: The cavernous body of the lacrimal sac and nasolacrimal duct plays an important role in the physiology of tear outflow regulation. It is subject to autonomic control and is integrated into a complex neuronal reflex feedback mechanism starting with the dense innervation of the cornea. Moreover, its function can be pharmacologically influenced.

TFF peptides in the human efferent tear ducts.

PURPOSE: To determine whether the lining epithelium of the human lacrimal sac and nasolacrimal duct synthesizes TFF peptides (formerly P-domain peptides, trefoil factors), a family of mucin-associated secretory peptides. METHODS: Expression of TFF peptides in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction and Western blot analysis. Antisera specific for TFF peptides were used in immunohistochemical analysis to determine the presence and distribution of all three TFF peptides in epithelia of the lacrimal passage. The samples investigated originated from tissue obtained during surgery (18 patients) and postmortem tissue (10 specimens). RESULTS: mRNA expression of TFF1 and TFF3, but not TFF2, was detected in human lacrimal sac and nasolacrimal duct. TFF1 was detected in only approximately 50% of the investigated probes, whereas TFF3 was present in all samples. Immunohistochemistry revealed TFF1 (if present) to be associated with goblet cells forming intraepithelial mucous glands. TFF3 occurred in epithelial cells of the lacrimal sac and the nasolacrimal duct as well as in the acinar cells of subepithelial serous glands, but appeared to be absent in goblet cells. CONCLUSIONS: The epithelium of the nasolacrimal ducts synthesizes TFF3 and in some cases also TFF1. In contrast to the human conjunctiva, in which TFF3 is detectable only in goblet cells, TFF3 of the lacrimal sac and nasolacrimal duct is produced in large amounts by epithelial cells as well as by serous glands, but not-or in small amounts only-by goblet cells. This is comparable with localization of TFF3 in the major salivary glands. Thus, TFF3 may have a special function in tear transport through the lacrimal passage comparable to its function on the ocular surface, because the peptide, together with TFF1, may contribute to the rheologic properties of the tear film. Moreover, the TFF peptides may also influence epithelial healing with their motogenic properties.

Animal model for the absorption of lipophilic substances from tear fluid by the epithelium of the nasolacrimal ducts.

PURPOSE: To compare the nasolacrimal tissues of several species to see how closely they resemble the human and to measure nasolacrimal absorption of a substance, to show that an absorption pathway exists for substances placed in the external eye, other than directly through the cornea or conjunctiva. METHODS: The nasolacrimal systems of six different vertebrates were investigated by light microscopy to find a species with a nasolacrimal system comparable to that of humans, for use in absorption experiments. In addition to primates, rabbits were revealed by histology to have a lacrimal system closely comparable to that of humans. The rabbit lacrimal system had a stratified epithelium consisting of two layers. Subepithelially, the lamina propria was composed of two strata: loose connective tissue containing elastic fibers and lymphatic cells and a rich venous plexus comparable to a cavernous body. Rabbits were therefore chosen for the absorption experiments. (3)H-cortisol was dropped into the eyes of female rabbits. After 21, 43, or 146 minutes, the rabbits were killed, the blood collected, and the nasolacrimal systems prepared and embedded for histologic examination. Serum was obtained from the clotted blood, and radioactivity was counted. Autoradiographs of sections of rabbit nasolacrimal duct were also prepared. RESULTS: Uptake of radioactivity into the serum was high and increased with time. After 21 minutes, maximum incorporation of the applied radioactivity into the blood the level was 7.1%; after 43 minutes, 12.4%; and after 146 minutes, 15.5%. Transport of radioactivity was visualized in autoradiographs of rabbit nasolacrimal systems. CONCLUSIONS: (3)H-cortisol is incorporated from the nasolacrimal ducts into the blood of rabbits. The comparable morphology of rabbits and humans suggests that absorption of cortisol would also take place in humans. Future investigations of the nasolacrimal passage are needed to understand whether absorption of normal tear fluid components in the nasolacrimal ducts is a physiological function that also plays a role in pathologic conditions such as dry eye. The similarities between rabbit and human nasolacrimal ducts support the use of the rabbit for such studies.

Characterization of mucins in human lacrimal sac and nasolacrimal duct.

PURPOSE: Mucins are polymers that may reduce drag and enhance tear outflow. Mucin expression and distribution in human efferent tear ducts were tested in the physiological state, and potential differences in the expression pattern were investigated in the presence of primary acquired dacryostenosis (PANDO). METHODS: Expression of mucins in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction analysis. The presence and distribution of MUC1, -2, -4, -5AC, -5B, -6, and -7 in epithelia of the efferent tear duct passage are assessed with antisera to mucin peptide cores. Twenty normal tissues from cadavers and surgical specimens from 20 patients with PANDO were tested. RESULTS: mRNAs for all mucins investigated were detected in healthy human lacrimal sacs and nasolacrimal ducts. MUC6 mRNA was detected in only about half of the investigated samples. A reduced level of MUC2, -5AC, and -5B mRNAs was observed in PANDO. Immunohistochemistry revealed MUC2 in goblet cells and single epithelial cells. Both MUC5AC and -5B were detected in goblet cells forming intraepithelial mucous glands. MUC7 was present only in columnar epithelial cells of the efferent tear duct system. No immunoreactivity was observed with antibodies against MUC1, -4, and -6 peptide cores. CONCLUSIONS: Human efferent tear ducts express and produce a broad spectrum of mucins that is partly comparable with that in the conjunctiva and the salivary glands. The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense. Reduced levels of mucin mRNA in a nonfunctioning though patent segment of the lacrimal passage, which is associated with epiphora, suggests that mucins ease tear flow through the efferent tear ducts.

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.

Loss of tear duct-associated lymphoid tissue in association with the scarring of symptomatic dacryostenosis.

OBJECTIVE: To determine whether organized mucosa-associated lymphoid tissue (MALT) is a normal component of the human efferent tear ducts or is acquired in reaction to chronic inflammation. DESIGN: Nonrandomized comparative (cadaver controlled) study with histopathologic correlations. MATERIALS: Tissue specimens from nasolacrimal ducts of 38 patients undergoing endonasal dacryocystorhinostomy in postinflammatory dacryostenosis with signs of chronic inflammation were analyzed using histologic examination and immunohistochemical studies. Only tissue specimens revealing proliferative sclerotic forms of chronic fibrosis were chosen for the study. Eighty specimens from the lacrimal systems of body donors served as controls. TESTING: Tissue specimens from each lacrimal system were prepared and processed with paraffin, sectioned, stained using different histologic methods with an array of specific antibodies, and examined by light microscopy. MAIN OUTCOME PARAMETERS: The distribution of intraepithelial and subepithelial defense cells was analyzed to identify plasma cells, secretory immunoglobulins, lymphocytes, dendritic cells, and organized mucosa-associated lymphoid tissue. RESULTS: The presence of secretory immunoglobulin A was demonstrated in subepithelial plasma cells and in the cytoplasm of apical epithelial cells in both chronically inflamed and healthy lacrimal systems. In more than one third of cases from body donors, but in only a few biopsy specimens from patients, organized lymphoid tissue was found with the cytomorphologic and immunophenotypical features of MALT. All other cases showed a diffuse infiltrate of defense cells within the lamina propria. CONCLUSIONS: The development of tear duct-associated lymphoid tissue (TALT) is a common feature that is often found in symptomatically normal nasolacrimal ducts. Because TALT seems to be lost associated with the scarring of symptomatic dacryostenosis, it is unlikely that the presence per se of TALT leads to scarring. Future studies are needed to explain the development of TALT.