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PubMed1983

Light and electron microscopic studies of malignant melanoma of conjunctiva and palpebra.

The authors experienced one case of malignant melanoma of the superior palpebral conjunctiva and the inferior palpebral skin, originating from benign acquired melanosis of the bulbar conjunctiva which developed in a 48-year-old man. Orbital exenteration including superior and inferior palpebrae was performed, and the removed tissue was examined by light and electron microscopy. In the temporal bulbar conjunctiva, melanocytes containing abundant fine melanin granules proliferated over almost the whole area of the epithelial layer. Cellular atypia and karyomitosis were not observed. The basement membrane remained intact with no proliferation of melanocytes in the substantia propria. However, in the perivascular area, in addition to the moderately prominent infiltration by lymphocytes and plasma cells, infiltration by melanophages was observed relatively frequently. Based on these findings, it was confirmed that the primary lesion of the bulbar conjunctiva was an acquired melanosis of Stage IB as classified by Zimmerman. The black nodular tumors of the superior palpebral conjunctiva and inferior palpebral skin consisted of melanoma cells showing markedly prominent cellular and nuclear atypia. The nuclei showed indentations in the membrane with electron-lucent karyoplasm, each having one nucleolus. The cytoplasm contained many round or elongated melanosomes in various developmental stages, with sizes of about 0.7 micron. Scattered among melanoma cells were a number of melanophages which had phagocytized many melanosomes at various stages of maturity.(ABSTRACT TRUNCATED AT 250 WORDS)

Conjunctival Neoplasms↗
PubMed1981

Goblet cells of the human conjunctiva.

We correlated histologic findings concerning conjunctival goblet cells with findings concerning the mucous membrane surfaces of the conjunctiva. Ten biopsy specimens were obtained from the upper tarsal conjunctiva and ten from the perilimbal bulbar conjunctiva. Changes in goblet cells just before and during secretion included changes in surface cell diameter, evagination of the apical surface of the cell membrane, decrease in the number of microvilli, and alteration in the arrangement and morphologic characteristics of microvilli. Changes seen by light and transmission electron microscopy correlated with those observed by scanning electron microscopy. Goblet cells were often associated with crypt openings; some crypts served as conduits for the secretion of mucus from underlying goblet cells. This study supports the hypothesis that crypts in the conjunctiva seen by scanning electron microscopy are often associated with goblet cells and their mucus secretion.

Adult↗
PubMed1988

Immunohistochemical markers in the normal human epibulbar conjunctiva from fetus to adult.

Monoclonal antibodies were used for the study of inflammatory cellular subtypes, Langerhans' cells, and major histocompatibility complex class II antigens on the epibulbar conjunctiva obtained from individuals ranging in age from fetus to the seventh decade to compile basic data for comparison with other inflammatory and proliferative conjunctival diseases. In the fetal conjunctiva, there were significantly fewer T cells and Langerhans' cells than in adult conjunctiva. In the adult conjunctiva, a mild T-cell infiltration was observed. Expression of HLA-DQ in the 20- to 50-year-old age group was significantly lower compared with fetal and other age groups.

Adolescent↗
PubMed1996

Streaming conjunctiva.

BACKGROUND: Epithelial proliferation is linked with cell displacement. When a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location that has to be vacated first by peripheral cells. As cells are neither pushed nor pulled in a mechanical sense, and since they do not move by their own means, this displacement is best regarded as streaming. The purpose of the present study was to measure epithelial cell streaming in adult rat conjunctiva. METHODS: Twenty-seven female adult rats were injected i.p. with 18.5 KBq [3H]-thymidine/g body weight, specific activity 185 GBq/mMol. Three rats were killed at different times up to 28 d. Eyes and eyelids were removed in one piece, cut along the pupillary-optic nerve line into 5-microns-thick sections, and prepared for autoradiography. In each eye, the entire upper conjunctiva extending from limbus to the palpebral muco-cutaneous junction was scanned with an ocular micrometer grid. The limbus served as point of origin. The x, y coordinate of each nucleus with two grains or more and its grain content were recorded. RESULTS: One hour after labeling, labeled cells were spread evenly along the basal layer. Cells of the upper layers were not labeled. As time passed by, labeled cells in the fornix became more abundant, while in the limbus and palpebral margin, their frequency declined. Labeled cells streamed from the limbus and palpebral muco-cutaneous junction to the fornix. Bulbar conjunctival epithelia streamed at a velocity of 13.2 microns/day. Epithelia in the palpebral conjunctiva streamed at a velocity of 11.8 microns/day. At the same time cells streamed from the basal layer to the epithelial surface at a velocity of 0.4 microns/day. Generation time was 3.9 days. CONCLUSIONS: Bulbar and palpebral conjunctivae are two independent cell kinetic systems that originate in two stem cell regions, one in the limbus and the other in the muco-cutaneous junction. Each system is made of two compartments, a progenitor where cells proliferate, and a compartment of non proliferating end cells. Progenitors created in the first, enter the second and turn into end cells. Ultimately they die in the fornix. The undetermined limbus stem cell generates two epithelial cell lines, a corneal and a conjunctival.

Animals↗
PubMed1999

Human conjunctiva contains high endothelial venules that express lymphocyte homing receptors.

Lymphocyte trafficking into tissues has been shown to occur across vessels with specialized endothelial cells called high endothelial venules. High endothelial venules naturally occur in lymph nodes and mucosal lymphoid tissues. The presence of high endothelial venules in the conjunctiva has not been demonstrated previously and the purpose of this study was to determine whether there is such a specialized vasculature to facilitate lymphocyte trafficking in conjunctiva associated lymphoid tissue.Samples of conjunctiva from four different individuals were analysed morphometrically for the presence of high endothelial venules by light and electron microscopy, and by immunohistochemistry using antibodies specific for high endothelial venules and for two adhesion molecules namely, Vascular Adhesion Protein-1 and Mucosal Addressin Cell Adhesion Molecule-1, expressed on high endothelial venules found in other tissues. Blood vessels with anatomical features of high endothelial venules were demonstrated in relation to conjunctival follicles and in the lamina propria. Immunohistochemical studies showed positive staining of vessels with anti-high endothelial venule antibodies, and with antibody against Vascular Adhesion Protein-1 but not with antibody against Mucosal Addressin Cell Adhesion Molecule-1. This study reveals that some of the blood vessels associated with conjunctival follicles and lamina propria have features of high endothelial venules. These vessels may play a significant role in lymphocyte homing to the conjunctiva and Vascular Adhesion Protein-1 (but not Mucosal Addressin Cell Adhesion Molecule-1) is one of the vascular addressin/adhesion molecules.

Cell Adhesion Molecules↗
PubMed1992

The source of sensory fibres of the inferior conjunctiva of monkeys.

Dissection, light and electron microscopy combined with degeneration induced by intracranial nerve lesions and superficial nerve transection were used to trace the sources of sensory fibres of the inferior conjunctiva of cynomolgus monkeys. Most nerves destined for the inferior conjunctiva were branches of the lacrimal nerve and entered the inferior eyelid laterally. Following unilateral ophthalmic neurotomy in three monkeys and combined ophthalmic/maxillary neurotomy in one monkey, substantial and regular degenerative changes were observed in the nerves and nerve-fibre bundles of the inferior conjunctiva. Following intracranial lesions of the maxillary nerve and of the infra-orbital nerve at its facial hiatus, conjunctival nerves showing induced changes were infrequent (four animals) or absent animal). The results indicate that the inferior conjunctiva is innervated mainly by the ophthalmic nerve contrary to the popular notion that it is innervated mainly or wholly by the infra-orbital branch of the maxillary nerve.

Animals↗
PubMed1994

The effect of preservatives and antiglaucomatous medication on the histopathology of the conjunctiva.

BACKGROUND: Topical medication applied chronically for the treatment of glaucoma changes the cellular profile of the conjunctiva. We wanted to determine the role of preservatives, which are usually combined with the drugs, on this effect. METHODS: We applied metipranolol 0.3% and pilocarpine 2% with and without benzalkonium chloride 0.01% and cetrimonium chloride 0.004%, respectively. Twenty-four rabbits, divided into four groups, were treated for 3 months. The complete globes and the adherent bulbar conjunctiva were examined histopathologically and immunohistochemically. RESULTS: With special stains for collagen, a slight increase of the thickness of subepithelial collagen of the conjunctiva was present in both groups treated with medication and preservative compared with eyes treated with medication alone. This effect was also true for special antibodies for collagen type IV and alpha-smooth muscle actin in the eyes treated with pilocarpine, but not in the eyes treated with metipranolol. CONCLUSION: The results suggest that preservatives may have an additional adverse effect on the conjunctiva in addition to the effects of the medications alone.

Actins↗
PubMedDate not supplied

Disodium cromoglycate inhibits capsaicin-induced eosinophil infiltration of conjunctiva independent of mast cells.

PURPOSE: To investigate whether disodium cromoglycate (DSCG) inhibits capsaicin-induced eosinophil infiltration of the conjunctiva independent of mast cells. METHODS: We administered 5 microl of capsaicin solution (10(-5) M) into the conjunctival sacs of mast cell-deficient W/W(v) mice (12 animals) and wild-type mice (12 animals). As controls, the eyes of 12 wild-type and 12 W/W(v) mice were treated with phosphate-buffered saline. Following treatment, the eyelids and eyeballs were removed en bloc at 3, 9, or 24 h, and were histologically examined. The number of infiltrated eosinophils and the expression of vascular cell adhesion molecule-l (VCAM-1) in the conjunctiva were quantified by the staining method of Hansel and immunohistochemical analysis. We also investigated whether treatment by depletion of neuropeptides or by DSCG administration could suppress the capsaicin-induced eosinophil infiltration of the conjunctiva. RESULTS: In both W/W(v) and wild-type mice, eosinophil infiltration of conjunctival tissues was observed 3 h after capsaicin administration. In both strains of mice, the number of infiltrated eosinophils increased over time, with VCAM-1 expression on vascular endothelial cells peaking at 9 h after treatment, and decreasing gradually within 24 h after treatment. In both the neuropeptide-depleted and the DSCG-treated groups, eosinophil infiltration and VCAM-1 expression were suppressed in comparison with the nontreated group. CONCLUSION: DSCG can directly inhibit neuropeptide-induced eosinophil infiltration of the conjunctiva independent of mast cells.

Animals↗
PubMed1976

Plasma cell content of main and accessory lacrimal glands and conjunctiva.

The size, weight, and plasma cell content of main and accessory lacrimal glands were examined and compared to the number of plasma cells in the conjunctiva. There were from four to 35 accessory lacrimal glands in the upper conjunctiva and a rare accessory gland in the lower conjunctiva. The total accessory gland mass was approximately one tenth of the lacrimal gland mass although the number of plasma cells was approximately 1/20 of the mass. The number of plasma-cells in the lacrimal gland was estimated to be 3,200,000; in the conjunctiva, 2,100,000; and for the accessory glands, 180,000. Because of the many plasma cells in the relatively inaccessible lacrimal gland, cells of the lymphatic series may home to the lacrimal gland by non-antigenic mechanisms.

Adult↗
PubMed1982

T-cell subsets and Langerhans cells in normal and diseased conjunctiva.

To identify the infiltrating mononuclear cells in conjunctival lesions, we stained frozen tissue sections of conjunctiva with a series of monoclonal antibodies against T cells and T-cell subsets with an immunoperoxidase method. In vernal conjunctivitis and ocular pemphigoid, most lymphocytes reacted with the anti-T4 antibodies that define helper/inducer T cells (T4+); a minority reacted with the anti-T8 antibody that defines suppressor/cytotoxic T cells (T8+). However, T8+ cells predominated in a conjunctival specimen from a patient with chronic graft-vs-host disease. A few T8+ cells and rare T4+ cells were also found in normal conjunctiva. In some diseased conjunctivas, there was an increase in cells stained with anti-T6 antibody, which stains Langerhans cells in normal conjunctiva and skin. T lymphocyte subsets and Langerhans cells probably play an important role in the pathogenesis of inflammatory conjunctival lesions.

Antibodies, Monoclonal↗
PubMed1986

Characterization of a localized basophil hypersensitivity lesion in guinea pig conjunctiva.

Basophils accumulate in response to antigen challenge in cutaneous basophil hypersensitivity (CBH) reactions. Two ocular diseases, vernal conjunctivitis and contact-lens-associated conjunctivitis, are also characterized by this histopathology. We have refined a model previously developed in guinea pig conjunctiva by precisely defining the site of antigen injection and correlating the site with the clinical and histologic changes. Guinea pigs were primed by an intradermal injection of keyhole limpet hemocyanin (KLH) in the flank and challenged (Day 6) by injection of a small bolus of KLH just under the conjunctival epithelium. Twenty-four hours later histologic examination showed a perivascular infiltrate of inflammatory cells containing large numbers of basophils. Eosinophils, neutrophils, macrophages, and mast cells were also seen. Serial sections of the reaction site showed discrete boundaries. At all sites examined in antigen-challenged tissues, there were significantly more basophils than in control-injected conjunctiva. Insertion of a sterile needle or injection of PBS or KLH into normal conjunctiva induced a significant increase in neutrophils and some macrophages. Injection of graded doses of antigen into the conjunctiva of primed animals, resulted in a dose-dependent increase in basophils up to 50 micrograms KLH (optimal dose).

Animals↗
PubMed1988

Lectin-cytochemical study on epithelial mucus glycoprotein of conjunctiva and pterygium.

The epithelium of pterygium and conjunctiva was studied with reference to cytochemical reactivity to six fluorescein-labeled lectins that recognize a certain carbohydrate residue(s) of cellular membrane-bound or secretory glycoprotein: Ulex europaeus agglutinin-1 (UEA-1, specific for fucose); Dolichos biflorus agglutinin (DBA, specific for N-acetylgalactosamine); peanut agglutinin (PNA, specific for galactose-beta 1-3N-acetylgalactosamine): wheat germ agglutinin (WGA, specific for N-acetylglucosamine and N-acetylneuraminic acid); Concanavalia ensiformis (Con A, specific for mannose); Ricinus communis agglutinin-1 (RCA-1, specific for galactose). Non-goblet epithelial cells of pterygium were labeled with UEA-1, DBA and PNA, while those of conjunctiva were not. Distribution density of goblet cells was larger in pterygium than in conjunctiva, but there was no distinct difference in lectin reactivity between the two tissues, with marked label with WGA, PNA and RCA-1. Con A did not bind to either pterygium or conjunctiva. The observations suggest the presence of anomalous mucus glycoproteins secreted from pterygium.

Aged↗
PubMed2006

Influence of age, gender and iris color on mechanical and chemical sensitivity of the cornea and conjunctiva.

The purpose of this study was to establish the influence of age, gender and iris color on the mechanical and chemical sensitivity of the cornea and the conjunctiva. In 57 healthy subjects (27 males, 30 females; ages between 23 and 71 years), sensory thresholds to mechanical and chemical stimulation were measured in the central cornea and the temporal conjunctiva using a Belmonte's gas esthesiometer. Mechanical stimulation consisted of warmed air pulses of 3s duration at different flow rates (40-200 ml/min). For chemical (acidic) stimulation, 3-s warmed gas pulses containing 10% to 80% CO(2) in air were applied, at a flow below mechanical threshold flow. Corneal and conjunctival thresholds to mechanical and chemical stimuli increased with age. Premenopausal women were more sensitive to corneal stimulation than men of similar ages but overall differences in mechanical and chemical threshold between men and women were not significant. Individuals with blue eyes had significantly lower corneal chemical thresholds than those with brown or green eyes. Multiple linear regression analysis evidenced that corneal mechanical threshold depends on age and iris color according to the equation 58.2 ml/min+1.3.(Age-23 years)-9.7 if blue eyes. For chemical threshold, the equation was 28.6%CO(2)+05.(Age-23 years)-12.5 if blue eyes. In the case of the conjunctiva, only age determined mechanical and chemical thresholds according to the equations: 78.2 ml/min+1.4.(Age-23 years) and 41.6%CO(2)+0.8.(Age-23 years), respectively. Therefore, normal values of mechanical and chemical thresholds of the cornea and conjunctiva measured with the Belmonte gas esthesiometer can be predicted according to age and iris color. Variations of sensitivity with age, iris color and gender may reflect differences in innervation density and neural responsiveness associated with the hormonal status.

Adult↗
PubMed2004

Ex vivo produced human conjunctiva and oral mucosa equivalents grown in a serum-free culture system.

PURPOSE: We sought to develop full-thickness ex vivo produced human conjunctiva and oral mucosa equivalents using a serum-free culture system without a feeder layer and to compare conjunctiva and oral mucosa equivalents to assess their suitability as graft materials for eyelid reconstruction. MATERIALS AND METHODS: Human conjunctival and oral mucosal keratinocytes were cultured, expanded, and seeded onto AlloDerm (LifeCell Corp, Branchburg, NJ), a cadaveric, acellular dermis, to produce ex vivo produced full-thickness mucosa equivalents. Histology of equivalents and their expression of immunoreactive Ki-67, a proliferation marker, and GLUT1, a membrane antigen seen in barrier tissues, were examined at 4, 11, and 18 days after seeding onto AlloDerm. RESULTS: Progressive epithelial stratification was observed on day 4, 11, and 18 conjunctiva and oral mucosa equivalents. Ki-67 immunoreactivity progressively increased with cultured time in both types of equivalent, indicating the continued presence of actively proliferating cells. GLUT1 immunoreactivity, concentrated in the basal keratinocytes of stratified epithelia of both types of equivalents, mimicked native tissue and indicated a high glycolytic state of the basal cells. CONCLUSIONS: Conjunctival and oral mucosal equivalents are similar to native tissue and demonstrate high proliferative and glycolytic states. Due to the similarity to conjunctiva, oral mucosal equivalents may be useful for eyelid reconstruction. Their advantages for surgical reconstruction include 1) ease of obtaining autogenous oral epithelium for expansion in vitro without the possibility of contaminating cellular- or serum-borne biologic agents, 2) growth of intact, confluent epithelia on rigid, transplantable human allogeneic dermis that may be surgically transplanted, and 3) reduced donor site morbidity and surgical time.

Biocompatible Materials↗
PubMed1999

Epithelial hyperproliferation and transglutaminase 1 gene expression in Stevens-Johnson syndrome conjunctiva.

In Stevens-Johnson syndrome, pathological keratinization of the ordinarily nonkeratinized corneal and conjunctival mucosal epithelia results in severe visual loss. We examined conjunctiva covering cornea in five eyes in the chronic cicatricial phase of Stevens-Johnson syndrome. Normal conjunctiva from five age-matched individuals was studied also. The number of epithelial cells in Stevens-Johnson syndrome conjunctiva that were immunoreactive with a monoclonal antibody, Ki-67, to a nuclear antigen found only in proliferating cells was greater than normal (93.8+/-19.8 cells above 100 basal cells versus 12.8+/-0.5 cells above 100 basal cells; P = 0.009). In addition, although clinical inflammation was mild, massive lymphocytic infiltration was seen in the substantia propria of conjunctiva covering cornea. In situ hybridization documented transglutaminase 1 (keratinocyte transglutaminase) mRNA in suprabasal cells of the abnormally thickened conjunctival epithelium in all Stevens-Johnson syndrome patients. In contrast, no message was detected in normal conjunctival or corneal epithelia. Transglutaminase 1 is expressed during the terminal differentiation of keratinocytes where it helps synthesize cornified cell envelopes. We speculate that in Stevens-Johnson syndrome, epithelial hyperproliferation, and transglutaminase 1 gene expression lead to the pathological keratinization of ocular surface mucosal epithelia.

Adult↗
PubMed2001

Proliferation and apoptosis in the epithelium of the developing human cornea and conjunctiva.

To determine the distribution of proliferating and apoptotic cells in the human cornea during prenatal and early postnatal development, we examined sections of the bulbar conjunctiva, the limbus as well as the central and peripheral cornea between 11 weeks of gestation and 6 months after birth. The objective was to localize dividing cells by proliferating cell nuclear antigen-like immunoreactivity (PCNA-LI) and apoptotic cells by terminal transferase-mediated nick-end labeling (TUNEL). Before the 17th gestational week, PCNA-LI was absent in all 4 regions examined, indicating negligible cell proliferation during early development. After 20 weeks, strong PCNA-labeling was observed in all regions examined suggestive of high proliferative activity not only in the limbus and the bulbar conjunctiva, but also in the central and peripheral cornea. This rise in proliferative activity was followed by a steady decline: after 28 weeks, anti-PCNA staining gradually disappeared in the central and peripheral cornea, so that, at 6 months after birth, it was confined to the limbus and the bulbar conjunctiva, resembling the picture described for the adult cornea. TUNEL-positive cells were virtually absent in all 4 regions examined before the 38th gestational week. Apoptotic cells only started to appear at 38 weeks; at this stage, they were confined to the bulbar conjunctival epithelium. At 6 months after birth, TUNEL-positive cells were observed in the bulbar conjunctival epithelium and the entire cornea; the limbus, however remained devoid of apoptotic cells throughout the entire prenatal and early postnatal period. The present study for the first time localizes proliferating and apoptotic cells in the epithelium of the developing human cornea. Three stages of development can be distinguished: Minimal proliferation (until 17th week), vigorous proliferation over the entire cornea including the limbus and the bulbar conjunctiva (until 28th week) and gradual decrease in proliferative activity (after 28th week) accompanied by the appearance of apoptotic cells.

Aging↗
PubMed2000

Pharmacological modulation of fluid secretion in the pigmented rabbit conjunctiva.

We determined net fluid secretion rate across the pigmented rabbit conjunctiva in the presence and absence of pharmacological agents known to affect active Cl- secretion and Na+ absorption. Fluid flow across a freshly excised pigmented rabbit conjunctiva mounted between two Lucite half chambers was measured by a pair of capacitance probes in an enclosed cabinet maintained at 37 degrees C and a relative humidity of 70%. Fluid transport was also measured in the presence of compounds known to affect active Cl- secretion (cAMP, UTP, and ouabain), Na+ absorption (D-glucose), or under the Cl--free condition on both sides of the tissue. Net fluid secretion rate across the pigmented rabbit conjunctiva in the serosal-to-mucosal direction at baseline was 4.3+/-0.2 microl/hr/cm2 (mean +/- s.e.m.). Net fluid secretion rate was increased approximately two-fold by mucosally applied 1 mM 8-Br cAMP (8.4+/-0.4 microl/hr/cm2) and 10 microM UTP (9.8+/-0.6 microl/hr/cm2), but was abolished by either serosally applied 0.5 mM ouabain (0.3+/-0.1 microl/hr/cm2) or under the Cl--free conditions (0.06+/-0.04 microl/hr/cm2). Mucosal addition of 20 mM D-glucose decreased net fluid secretion rate to 1.0+/-0.5 microl/hr/cm2. In conclusion, the pigmented rabbit conjunctiva appears to secrete fluid secondary to active Cl- secretion. This net fluid secretion is subject to modulation by changes in active Cl- secretion rate and in mucosal fluid composition such as glucose concentration.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Drug-induced cicatricial pemphigoid affecting the conjunctiva. Light and electron microscopic features.

Cicatricial pemphigoid (CP) is a chronic inflammatory disease which can affect the conjunctiva. It is a slowly progressive disorder of unknown but presumed autoimmune etiology. Pseudopemphigoid, or CP associated with ocular drug administration, has also been described. These cases, which appear clinically indistinguishable from unilateral idiopathic CP affecting the conjunctiva, have been related to the use of echothiophate iodide, pilocarpine, idoxuridine, and epinephrine. We report the histopathologic and ultrastructural characteristics of 22 biopsies from ten patients with iatrogenic CP following the use of various ocular drugs. All patients presented with clinically obvious, active CP affecting the conjunctiva. Light microscopy and electron microscopy revealed findings identical to those previously reported for idiopathic CP of the conjunctiva: squamous metaplasia, increased numbers of desmosomes, basal lamina modifications suggestive of damage and attempted repair, subepithelial inflammatory cell infiltration, and diminished intravascular space within the stroma. These patients responded to immunosuppressive therapy. The authors wonder if it is possible that these patients were destined to develop CP, but that with topical ocular drug use, a more rapid emergence of the chronic cicatrizing feature of CP developed.

Aged↗