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PubMed1994

Airway goblet cells: responsive and adaptable front-line defenders.

Goblet cells are situated in the epithelium of the conducting airways, often with their apical surfaces protruding into the lumen, a location which fits them for a rapid response to inhaled airway insults. Together with the submucosal glands, goblet cells secrete high molecular weight mucus glycoproteins (mucins), which confer upon the airway surface fluid the requisite biochemical and biophysical properties which determine the efficiency of entrapment and transportation of inhaled irritants, particles and micro-organisms. The diversity of glycosylation of airway mucins may be important in facilitating adherence of micro-organisms to mucus prior to mucociliary clearance. Other secretory products, including lipids and "small" glycoproteins, may also be produced by goblet cells. It is possible that goblet cells have the potential to produce markedly more mucus than do the glands. Mucins are tightly packed in the intracellular granules of the goblet cell. The morphology of these granules varies with fixation technique, and release of mucins may be via a combination of merocrine and apocrine secretion. Discharge of mucus is accomplished remarkably rapidly (tens of milliseconds) and vast quantities of mucus are released (size expansions from the granule of many hundredfold). Depending upon species and preparation, goblet cells discharge mucus in response to a wide variety of stimuli, including proteinases, irritant gases, inflammatory mediators, reactive oxygen species, nerve activation and changes in the biophysical environment. Under normal conditions, goblet cell proliferation and differentiation, particularly to ciliated cells, contributes to maintenance of the airway epithelial cell population. In addition to participating in acute airway defence, goblet cells increase in number in response to chronic airway insult, with a resultant increase in output of mucus. The increase in number of cells is via hyperplastic and metaplastic mechanisms. Early triggers for the development of a hypersecretory epithelium include excessive discharge of mucus and increased expression of airway mucin messenger ribonucleic acid (mRNA). Cessation of chronic airway stress rapidly reverses the increased number of goblet cells. Irritant-induced increases in number of goblet cells can be inhibited by a variety of drugs with anti-inflammatory and mucoregulatory properties, and the reversal to normal numbers after cessation of the irritation is speeded by these drugs. The ability of goblet cells to be progenitors of ciliated cells, to rapidly produce vast quantities of mucus in response to acute airway insult, and to change in number according to variations in chronic insult indicates that these cells are vitally important responsive and adaptable front-line defenders of the airways.

Animals↗
PubMedDate not supplied

Signet ring adenocarcinoma metastatic to the bronchus and mimicking goblet cell hyperplasia. A case report.

BACKGROUND: Goblet cells in the lower respiratory tract are metaplastic bronchial epithelial cells usually associated with asthma or chronic bronchitis. Goblet cells acquire their name by a tendency to distend with mucus, with subsequent distortion in cell shape. Due to similarity of shape, metaplastic goblet cells and signet ring cells can be easily confused in cytologic samples. CASE: A 55-year-old male with a history of gastrointestinal adenocarcinoma underwent brushing, washing and biopsy of a bronchial lesion. The bronchial wash and brush samples showed a very cellular specimen, with large aggregates of distended columnar cells. These were arranged in long strips, thick bundles and occasional three-dimensional aggregates. Some aggregates contained numerous rounded cells with markedly distended cytoplasm. The rounded cells were slightly larger than the distended columnar cells. These cells had a relatively large but innocuous-appearing nucleus displaced to the periphery of the cell. The corresponding bronchial biopsy revealed signet ring adenocarcinoma, presumably metastatic from the gastrointestinal primary. CONCLUSION: Signet ring adenocarcinoma, either primary or metastatic, can be difficult to diagnose in cytologic and histologic specimens. There are numerous mimics of signet ring cells, both benign and neoplastic. In respiratory cytologic specimens, one of the benign imposters is goblet cell metaplasia.

Bronchial Neoplasms↗
PubMed1997

The effects of disposable daily wear contact lenses on goblet cell count.

PURPOSE: The number of goblet cells on the inferior bulbar conjunctiva increases in response to daily wear contact lens use. We conducted a study to examine whether daily wear soft contact lenses worn on a 2-week disposable schedule would also induce the same goblet cell response. METHODS: Twenty-eight subjects who had never worn contact lenses were fit with 38% water polymacon lenses. The lenses were worn on a daily wear basis and replaced every two weeks over a 6-month period. Goblet cell count was determined by impression cytology of the inferior bulbar conjunctiva. RESULTS: No significant increase in goblet cell count was observed in the subjects during the 6 months period; the 3.23% baseline goblet cell count was never exceeded. In our previous study, after 6 months of conventional daily wear lens use, the goblet cell count increased from a baseline of 4.19% to 8.0%. CONCLUSIONS: It appears that wearing daily wear soft contact lenses on a disposable basis may be less irritating to the ocular surface than wearing soft contact lenses on a conventional daily wear basis.

Adolescent↗
PubMed1984

Regulation of intestinal goblet cells in situ, in mucosal explants and in the isolated epithelium.

Cholinergic secretagogues were previously shown to accelerate mucin secretion from intestinal goblet cells of adult rats and rabbits, both in vitro and in mucosal explants. This rapid secretory response occurs only in crypt cells; surface goblet cells are not affected. Rapid secretion involves the sequential fusion of secretory granule membranes with the plasma membrane and with each other, but does not require granule movement. In unstimulated cells, slow transport of secretory granules towards the luminal cell surface depends on functional microtubules. Goblet cells appear in the rat fetal intestine three to four days before birth but they are insensitive to cholinergic agents in the fetus and neonate. The secretory response of crypt goblet cells to carbachol, both in vivo and in mucosal slices in vitro, is established throughout the intestines only after weaning (20-25 days after birth). To determine whether acetylcholine from nerve endings in the intact mucosa may mediate a mucus secretory response in the absence of exogenous secretagogues, mucosal sheets were mounted in modified Ussing chambers and goblet cell secretion was assessed after electrical field stimulation. Electrical field stimulation elicited mucus secretion from crypt (but not surface) goblet cells. Secretion was inhibited by prior treatment of the mucosa with 500 nM-tetrodotoxin or 100 microM-atropine, but not by 10 microM-atropine. Thus, endogenous nerves may regulate mucus secretion from crypt goblet cells in the intact mucosa. When intact sheets of epithelium were isolated from adult rat ileum and colon, then maintained in vitro and exposed to 20 microM-carbachol, crypt goblet cells released mucin in response to the secretagogue but goblet cells in in portions of the epithelium derived from villi or mucosal surfaces were unresponsive. This suggests that crypt epithelial cells respond directly to cholinergic agents and that they lose this sensitivity as they migrate out of the crypts.

Animals↗
PubMed2006

Management of goblet cell carcinoid.

BACKGROUND AND OBJECTIVES: Goblet cell carcinoid, a rare tumor of intermediate malignant potential, is known to account for a significant minority of appendiceal neoplasms. Sixteen new cases of gastrointestinal goblet cell carcinoid were reviewed to describe their presentation, treatment, and outcome. METHODS: A review of 16 cases from a single institution. RESULTS: Sixteen patients were diagnosed with goblet cell carcinoid between 1995 and 2005. Presenting diagnoses included appendicitis (n=8), abdominal or liver mass (n=5), uterine fibroids (n=1), ovarian mass (n=1), and Crohn's Disease exacerbation (n=1). Mean follow-up was 12 months with a mortality of 19% (n=3). Patients were divided into two groups: those where the diagnosis was an incidental finding at operation (Group 1) and those where the presentation was of an abdominal mass or metastatic disease (Group 2). Nine of ten patients in Group 1 initially received appendectomies. Group 2 included patients presenting with Krukenberg type lesions (n=2) and abdominal masses (n=4). CONCLUSIONS: Goblet cell carcinoid is a rare malignant tumor largely affecting the appendix. In patients presenting with appendicitis, our series does not support the recommendation of right hemicolectomy based on pathologic diagnosis alone and surgical intervention must be customized to the individual patient.

Adult↗
PubMed1988

Goblet cell isolation from cat trachea: a comparison of methods.

Goblet cell hyperplasia and metaplasia may be important in the pathogenesis of many respiratory diseases. To study the intracellular mechanisms of mucin synthesis, a purified goblet cell preparation is necessary. We have compared different methods of cell dissociation using cat trachea, a source rich in goblet cells. The most successful method used EDTA to loosen the basement membrane and 1% pronase to dissociate the epithelial cells. Goblet cells recovered from a linear Percoll gradient showed preservation of their ultrastructural detail, trypan blue exclusion, oxygen consumption, and synthesis of a high molecular weight compound resistant to hyaluronidase degradation, consistent with mucous glycoprotein. This method allows the isolation of adequate numbers of purified goblet cells for further study of goblet cell synthetic processes.

Animals↗
PubMed2001

Presence of nerves and their receptors in mouse and human conjunctival goblet cells.

PURPOSE: To determine whether neural pathways for controlling goblet cell secretion are present in mouse and human conjunctiva. METHODS: Mouse conjunctiva was homogenized and subjected to electrophoresis and Western blotting to detect PGP 9.5 (indicates nerves), muscarinic receptor subtypes (indicates parasympathetic pathway), and adrenergic receptors (indicates sympathetic pathway). Mouse eyes and human conjunctival tissue were analyzed by immunofluorescence microscopy. Antibodies to vasoactive intestinal peptide (VIP), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and muscarinic and alpha(1)- and beta-adrenergic receptor subtypes were used. RESULTS: Western blot demonstrated PGP 9.5, M(1), M(2), and M(3) muscarinic receptors and alpha(1A)-, beta(1)-, beta(2)-, and beta(3)-adrenergic receptors in mouse conjunctiva. Immunoreactivity for VIP, TH, and DBH was found adjacent to mouse and human goblet cells. M(1) and M(2) muscarinic receptors were identified throughout mouse conjunctiva, but M(3) receptor was predominantly on goblet cells. All three muscarinic receptor subtypes were detected on goblet cells in human conjunctiva. alpha(1A)-Adrenergic receptors were found on epithelial cells and on goblet cells in mouse and human conjunctiva. beta(1)- and beta(2)-Adrenergic receptors were found on both epithelial and goblet cells in mouse conjunctiva, but not on human conjunctival cells. beta(3)-Adrenergic receptors were found on both epithelial and goblet cells in human conjunctiva but not on mouse conjunctival cells. CONCLUSIONS: The following conclusions were drawn: parasympathetic nerves and M(1), M(2), and M(3) muscarinic receptors, as well as sympathetic nerves are present on mouse and human goblet cells. The adrenergic receptors beta(1) and beta(2,) but not alpha(1A) and beta(3) are present on mouse conjunctival goblet cells, whereas alpha(1A) and beta(3,) but not beta(1) and beta(2) are present on human conjunctival goblet cells, suggesting that these nerves and receptors could activate goblet cell secretion in mouse and humans.

Aged↗
PubMed1989

Nasal polyps: epithelium and goblet cell density.

The density of goblet cells was determined in 14 anterior and 15 posterior nasal polyps using the whole-mount method. The specimens were then serial cut and the type of epithelium was determined in nine localities in each polyp. The goblet cell density was correlated to the epithelial type. Pseudostratified, cylindrical epithelium was the prevailing type, occurring in 62% of anterior localities and 78% of posterior localities. Transitional types of epithelium were found in 33% of the anterior and 19% of the posterior localities. Stratified squamous epithelium occurred in 5% and 3%, respectively. The goblet cell density was highest in hyperplastic pseudostratified epithelium, whereas it was four times lower in transitional epithelium and even lower in squamous epithelium. Marked differences in the distribution of epithelium and goblet cell density were found between anterior and posterior polyps, illustrating that the epithelium constantly changes under the influence of air current, contact with other polyps, infection, growth, and age of the polyp as well as other unknown factors.

Cell Count↗
PubMed1995

Colon goblet cells lose proliferative response to TGF alpha as they differentiate.

Two cell line models for colon goblet cells expressed 6- to 14-fold elevated levels of the EGF receptor, 3- to 5-fold levels of TGF alpha and 11- to 15-fold levels of amphiregulin compared with 2 cell lines which model colon enterocytic differentiation, suggesting a role for the EGF receptor and its ligands in goblet cell growth control. Two HT29 colon carcinoma sublines were used to model normal goblet cells at different stages of maturation. TGF alpha induced a 2-fold increase in growth of the HD8 subline but inhibited the growth of the more differentiated HD6 subline by 40%. EGF receptors were activated in each line by ligand, but signal transduction varied sharply. Both MAP kinase isoforms, p44 and p42, were markedly activated in HD8 cells for at least 20 min, while only a marginal activation was seen in HD6 cells. In contrast, the more differentiated HD6 cells showed an increase in 105 kDa MBP kinase activity with EGF treatment, while HD8 cells displayed constitutively elevated levels of this kinase. Thus, activated EGF receptors initiated different signalling pathways in model cell lines for colon goblet cells at different stages of maturation. TGF alpha protein levels have been shown by other investigators to be restricted to the top of the cylinder-like colonic crypt, where cells terminally differentiate and cease division, an unexpected location for an epithelial cell mitogen. Our data with model cell lines imply that normal colon goblet cells lose proliferative response to TGF alpha as they differentiate and the elevated levels of TGF alpha at the top of the colonic crypt in vivo serve to inhibit goblet cell growth.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2006

OPC-12759 increases proliferation of cultured rat conjunctival goblet cells.

PURPOSE: To determine if the gastroprotective drug OPC-12759 increased proliferation of rat conjunctival goblet cells in culture. METHODS: Cultured goblet cells were incubated with 10(-12) to 10(-8) M OPC-12759 for 1 to 7 days. Fetal bovine serum (FBS) was used as a positive control. Cell proliferation was determined by a MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] colorimetric assay and by immunohistochemical staining with anti-Ki-67, a marker of cell division. Goblet cells were identified by double-labeling with anti-Ki-67, a marker of cell division, and Ulex europaeus agglutinin I lectin, anti-MUC5AC and anticytokeratin 7. Stratified squamous cells were identified by using Griffonia (Bandeiraea) simplicifolia lectin and anticytokeratin 4 antibody. RESULTS: As determined by MTT conversion to formazan, OPC-12579 at 10(-11) M induced an almost 2-fold increase in goblet cell proliferation on Days 1 and 3 of incubation but not on Days 5 and 7. The FBS at 10% increased cell proliferation by 2- to 3-fold at each time point. Daily replenishment of OPC-12579 for 3 consecutive days induced cell proliferation at all concentrations. Proliferation as determined by the number of Ki-67 positive cells increased by 4- and 3-fold at Days 1 and 3, respectively with addition of 10(-11) M OPC-12579. The FBS at 10% induced a 10-fold increase in goblet cell proliferation on Days 1, 3, and 5. Colocalization of Ulex europaeus agglutinin I, MUC5AC and anticytokeratin 7 with Ki-67 indicated that proliferating cells were goblet cells. Proliferating cells were negative for the nongoblet cell markers Bandeiraea lectin and anticytokeratin 4. CONCLUSIONS: The OPC-12759 stimulates proliferation of conjunctival goblet cells in primary culture.

Alanine↗
PubMed1984

Kinetics of intestinal lamina propria mast cells, globule leucocytes, intraepithelial lymphocytes, goblet cells and eosinophils in murine strongyloidiasis.

The changes in numbers of 6 cell populations in the intestine of mice at various intervals after primary and challenge infections with Strongyloides ratti have been quantified. The number of lamina propria mast cells increased 8 days after primary infection and reached a peak at 12 days. After secondary infection, there was a transient fall in mast cell numbers followed by a slow increase. Globule leucocytes showed a similar trend early in the primary infection and had reached normal levels after 28 days. After challenge infection, there was an early and rapid increase in their numbers. Granular intraepithelial lymphocytes did not alter significantly during the first 14 days, but were significantly greater 28 days after primary infection; they did not vary significantly after challenge infection. However, numbers of non-granular intraepithelial lymphocytes increased 10 days after infection, were elevated prior to the secondary infection at 28 days, then declined in numbers nearly 2 weeks after challenge infection. Goblet cells increased significantly 12 days after primary infection then declined rapidly. After challenge infection, there was an accelerated increase in numbers. Eosinophil numbers increased 4 days after infection, reached a peak at 12 days and then declined. After challenge infection, there was an augmented and accelerated increase in eosinophil numbers followed by rapid decline. The role of the various cells types in host defences against worms or in containment of the inflammatory responses evoked by these parasites are discussed.

Animals↗
PubMed1984

Conjunctival goblet cell densities in ocular surface disease.

Goblet cell densities were determined in the eyes of normal subjects and in the eyes of patients with various ocular surface diseases using an impression cytological technique. For normal eyes goblet cell densities on the interpalpebral bulbar and inferior palpebral ocular surfaces were 443 (+/- 266 [+/- SD]) and 1,972 (+/- 862) cells millimeter, per square, respectively. All patients in the ocular surface disease groups had decreased goblet cell densities compared with subjects with normal eyes. Compared with normal eyes, eyes with keratoconjunctivitis sicca (KCS) demonstrated a 17% greater goblet cell loss on the interpalpebral bulbar compared with the inferior palpebral ocular surface, while eyes with blepharitis and secondary KCS demonstrated an 8% greater loss on the inferior palpebral surface compared with the interpalpebral bulbar ocular surface. Eyes with cicatricial ocular pemphigoid and Stevens-Johnson syndrome demonstrated greater than 95% goblet cell loss on both the interpalpebral bulbar and inferior palpebral ocular surfaces compared with normal eyes.

Adolescent↗
PubMed1992

Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically-induced goblet cell secretion in guinea-pig trachea.

1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta-opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4. DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO.5. We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.

Animals↗
PubMed1981

Ultrastructural studies on the secretory mechanism of goblet cells in the rat jejunal epithelium.

Goblet cells in the jejunal epithelium of adult and suckling rats were studied with transmission electron microscope. The use of triple fixation, i.e. osmium-aldehyde-osmium has some advantages in the preservation of mucous substances and some cell organelles. Cytochemical demonstration of polysaccharide and glycoprotein by methenamine silver as well as detection of TPPase and acid phosphatase (AcPase) were performed. Accumulation of secretory substances and combination with sugar moieties occurred in the internal sacs of Golgi lamellae, where TPPase activity was recognized. No rigid lamella usually positive to AcPase was found in goblet cells, though it was easily found in the columnar absorptive cells. AcPase was positive in some small immature mucus droplets as well as lysosomes. As the differentiation of goblet cells advances, mucus droplets come into contact and fuse to each other. As a result of the close contact of two adjacent membranes of mucus droplets, a pentalaminar structure is first formed. Then the central dense lamina disappears and the membrane becomes trilaminar. Disappearance of one of the apposed unit membranes, leaving another unit membrane, may take place. Finally the single unit membrane left between the adjacent droplets is also ruptured and complete fusion occurs. The mechanism of extrusion of mucous substance is complicated. Some mucus droplets located at the most superficial area may be released by the mechanisms of exocytosis. More frequently, however, deeply located droplets fuse to each other and a huge vacuole is made in the apical cytoplasm. The substance filling the vacuole contains debris of cytoplasmic matrix and droplet membranes along with mucous secretory substance. These substances derived from different sources are expelled into the lumen at the same time. This may be classified into the apocrine mechanism, because a part of the cytoplasm and membrane are lost. The typical apocrine secretion, i.e. pinching off of cytoplasmic projection containing mucus droplets, was also found in the goblet cells. Thus, two or three different mechanisms of secretion discharge may possibly occur simultaneously in goblet cells.

Acid Phosphatase↗
PubMed1984

Relationship between goblet cells and carcinoma of the pancreas during N-nitrosobis(2-hydroxypropyl)amine-induced carcinogenesis in Syrian golden hamsters.

During N-nitrosobis(2-hydroxypropyl)amine-induced pancreatic carcinogenesis in Syrian golden hamsters, both carcinoma and dysplasia could be distinctly classified into two types according to whether they did or did not contain goblet cells. Goblet cell-containing dysplasia developed mainly in the larger duct, and majority of goblet cell-containing carcinomas showed a pattern of papillary adenocarcinoma. It seems most probable that goblet cells are predysplastic and precancerous changes. On the other hand, dysplasia without goblet cells developed mainly in the smaller ductules, and a majority of carcinomas without goblet cells showed a pattern of poorly differentiated adenocarcinoma. These findings seem to correspond well with the relationship between human pancreatic cancer and mucus-secreting cells. The behavior of the goblet cells of hamster pancreatic ducts might be a good model for that of human mucus-secreting cells, especially mucous cells.

Animals↗
PubMed1988

Lectin histochemistry of goblet cells in metaplastic epithelium of human gallbladder.

Goblet cells arising in the intestinal metaplasia of chronically inflamed gallbladder were studied by lectin histochemistry and compared with equivalent cells in the small and large intestine. Overall, metaplastic goblet cells reacted more avidly with the majority of lectins and even expressed receptors for lectins that were unreactive with normal intestinal goblet cells. There was, however, considerable variation in lectin binding from one case to another, as well as among the cells of the same specimen. We thus conclude that metaplastic goblet cells in the gallbladder are different from normal intestinal goblet cells, but do not have a uniform lectin binding profile.

Cell Differentiation↗
PubMed2002

Trefoil peptide expression and goblet cell number in rat intestine: effects of KGF and fasting-refeeding.

The trefoil factor family peptides TFF1, TFF2, and TFF3 are important for gut mucosal protection and restitution. Keratinocyte growth factor (KGF) stimulates proliferation and differentiation of epithelial cells with potent effects on goblet cells. To investigate interactions between food intake and KGF, rats were fed ad libitum (control), fasted for 72 h, or fasted for 72 h and then refed for 72 h with or without KGF (3 mg. kg(-1). day(-1)). With fasting, goblet cell number in duodenum increased, TFF3 mRNA in duodenum and jejunum decreased, and TFF3 protein did not change or increased. KGF during fasting stimulated colonic growth, normalized TFF3 mRNA in duodenum and jejunum, and broadly upregulated gut goblet cell number and TFF3 protein expression. With fasting-refeeding, KGF increased small bowel and colonic mucosal growth, goblet cell number, and TFF3 protein but had variable effects on TFF3 mRNA. KGF induced TFF2 mRNA and protein in duodenum and jejunum with both nutritional regimens. We conclude that nutrient availability modifies rat intestinal goblet cell number, TFF3 mRNA, and the gut-trophic effects of KGF in a region-specific manner. KGF enhances TFF2 expression in proximal small bowel and increases goblet cell number and TFF3 protein content throughout the intestine independent of food intake.

Animals↗
PubMed1989

Differential staining of ocular goblet cells.

Millipore filters were used to obtain sheets of cells from the ocular surface. Using Periodic Acid Schiff-haematoxylin the intracellular neutral mucus of the goblet cells stains a brilliant, bright pink and the cell nuclei dark blue making it possible to observe the epithelial cells and the goblet cell population. In certain ocular surface diseases the size of the PAS-haematoxylin staining goblet cell population is reduced, returning towards normal as ocular health improves. These observations had previously been interpreted as showing degeneration followed by regeneration of the goblet cells. However, Alcian blue stains an acidic mucus, which does not stain with PAS-haematoxylin. Acidic mucus containing goblet cells have been revealed using Alcian blue staining when added to the PAS stained cells in conditions that have previously been shown to have reduced goblet cell population when assessed by PAS-haematoxylin staining. This suggests that the staining properties of some of the goblet cells have changed. The extra goblet cells revealed by Alcian Blue staining makes the total of goblet cells present close to normal in numbers. Improved clearing methods and cytological preservation has revealed that there is also a population of goblet cells that do not stain with either technique. These observations must cast doubts on previous claims of reduced goblet cell population associated with some extraocular diseases.

Conjunctiva↗