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Cyclooxygenase and lipoxygenase pathways in anterior uvea and conjunctiva.

It has been demonstrated that normal, uninflamed, anterior uvea and conjunctiva of different species have the capacity to synthesize cyclooxygenase and lipoxygenase products. Cyclooxygenase activity is greater than lipoxygenase activity in both anterior uvea and conjunctival tissues. Other ocular tissues such as cornea, lens, and retina were found to have much lesser capacity than the conjunctiva and anterior uvea to synthesize cyclooxygenase and lipoxygenase products from arachidonic acid. In our preliminary studies, we also observed that human retina have considerably less ability to metabolize AA into cyclooxygenase and lipoxygenase activity. The finding that the anterior uvea of all species studied has a high capacity to synthesize PGs and other cyclooxygenase products maybe of particular physiological significance since several investigators have demonstrated that PGE2 and PGF2 alpha in low doses, lower intraocular pressure in all species studied, including the human eye. Additionally, PGE2 can be shown to have some anti-inflammatory effects. In light of these observations, we must consider that the high endogenous cyclooxygenase activity in normal conjunctiva and anterior uvea may play a role in maintaining normal intraocular pressure and in preventing the development of inflammation in response to normal environmental stimuli. Arachidonic acid is also metabolized into biologically active compounds by cytochrome P450 in corneal endothelium. It is not yet known whether or not other ocular tissues also have the ability to metabolize arachidonic acid via this pathway and whether these compounds, when synthesized from endogenous arachidonic acid stores in vivo have any biological effects on the eye. Studies on omega-3 fatty acid metabolism were done for two main reasons: (1) PGE3 and PGD3 lowered intraocular pressure without causing ocular inflammation in rabbit; and (2) some surveys demonstrated that in Greenland Eskimos whose marine diet is enriched with omega-3 substrate eicosapentaenoic acid, have a lower incidence of open-angle glaucoma as compared to Caucasians, whose diet is rich in arachidonic acid. The ability of anterior uvea to synthesize PGE3 and PGD3 in human, monkey, and rabbit anterior uvea warrants further investigation to determine whether or not these omega-3 PGs play a role in lowering intraocular pressure.

Animals↗

[Status of the microcirculatory bed of the bulbar conjunctiva in various forms of vestibular dysfunction].

Using biomicroscopy of the eye conjunctiva, blood microcirculation was investigated in 200 patients with vestibular dysfunction (cervical osteochondrosis, Ménière's disease, neurocirculatory dystonia). All the patients showed microcirculation changes such as arteriolar spasms, reduced number of functioning capillaries, congestion and convolution of venules of medium and small caliber, and red blood cell aggregation. Capillary blood flow was intermittent: dash-dotted or bead-like. The arteriovenular coefficient decreased. Blood microcirculation changes were detected on the normal and affected sides of patients with cervical osteochondrosis, mostly on the affected side of patients with Ménière's disease, and on both sides of patients with neurocirculatory dystonia. Short-term changes in blood flow of vertebral arteries caused by head movements led to reflex responses of blood microcirculation of the conjunctiva. These reactions were most distinct in patients with cervical osteochondrosis and Mérière's disease. Eye conjunctiva biomicroscopy carried out during provocative tests with head movements may be used as a diagnostic test for identifying the type of vascular changes (vasoparetic or vasospastic) in vestibular dysfunction.

Conjunctiva↗

[Comparative analysis of the drinking behavior of rats after microinjections of angiotensin II and bradykinin into the cerebral ventricles and instillations on the conjunctiva of the eye].

The effects of angiotensin-II and bradykinin intracerebroventricular microinjections and instillations on the conjunctiva on water and alcohol consumption in rats were compared. The identical effects of peptide instillations on the conjunctiva and intracerebroventricular microinjections were demonstrated. Dipsogenic doses of angiotensin-II for instillations on the conjunctiva in intact rats were greater than or equal to 10 micrograms. At the same time the effective peptide doses in drinking rats were similar to intracerebroventricular drug doses.

Alcohol Drinking↗

Scanning electron microscopy study of human cornea and conjunctiva in normal and various pathological conditions.

Relatively few morphological studies on human cornea have been performed due to the difficulty in obtaining material. The specimens may be obtained either by superficial scraping-off, limited to the epithelial layer, or from corneal buttons obtained at keratoplasty. Conjunctiva, on the other hand, may be obtained by painless biopsy. We have studied the three-dimensional ultrastructure of the normal cornea and conjunctiva and in the course of various diseases where the application of scanning electron microscopy (SEM) seemed to be useful. In the cornea, we studied Fuchs' endo-epithelial dystrophy. In the conjunctiva, we analysed the ultrastructural characteristics of adenovirus follicular conjunctivitis, hay fever conjunctivitis and keratoconjunctivitis sicca. We also considered the problem of contact lens wearing, studying by SEM both the conjunctival tissue and the discarded lenses. On the basis of our results we conclude that SEM supplies useful information which integrates that obtained by biomicroscopy, used by clinicians to interpret the lesions at microscopic level. It is, however, indispensable to carry out, in addition to SEM, an examination on sections to completely investigate the disease.

Conjunctiva↗

[Taxonomy of the microangiological changes in the ocular conjunctiva].

By means of biomicroscopical investigations of bulbar conjunctiva in healthy persons of different age certain characteristics on normal microcirculatory bed have been obtained. Morphometric analysis of the vital microscopical observations has revealed some age peculiarities in microcirculation of the conjunctiva. As a result of clinical examination of the persons, it has been stated that the phenomena noticed at biomicroscopy which characterize certain anomalies of microcirculatory parameters correlate with latent pathology, closely related diseases or developmental anomalies. Therefore, it is possible to consider the method of biomicroscopical investigation of the conjunctiva with a subsequent morphometric analysis of the data obtained as suitable for application not only for clinical but also for prophylactic examination of healthy persons.

Adolescent↗

[Sources of the blood supply to the human bulbar conjunctiva].

In 93 complex preparations of the human orbit, the sources for blood supply of the eyeball conjunctiva, types of orbital vessels, including size of their diameters, were studied. The open parts of the conjunctiva were stated to get arteries of greater diameters comparing to those supplying the subconjunctival parts. It was noted that some sources of blood supply take their origin from the external carotid artery. This fact should be taken into account when choosing the part for biomicroscopy of the eyeball conjunctiva vessels.

Arteries↗

Immediate hypersensitivity in the guinea pig conjunctiva intravitreal and topical sensitization.

The right eyes of guinea pigs were injected with 1.5 mg sterile ovalbumin. Two months later, one drop of ovalbumin (approximately 0.6 mg) was applied to the conjunctiva of both eyes. All challenged eyes developed an immediate hypersensitivity reaction within 5 min. The reaction subsided within 2 hrs. Prechallenge antibody titers, as determined by passive hemagglutination, passive cutaneous anaphylaxis, and by an ELISA test were low. Titers rose rapidly after two conjunctival applications at weekly intervals. The hypersensitivity reaction was elicited each time antigen was applied to the conjunctiva of the intravitreally sensitized guinea pigs. Control guinea pigs received weekly conjunctival application of ovalbumin, without prior intravitreal sensitization. Most animals developed an immediate hypersensitivity reaction following the fourth application of the antigen. There was no detectable hemagglutinating or ELISA (IgG1, IgG2) antibody at the time the conjunctival reaction was first elicited. These experiments demonstrated that high circulating IgG1 or IgG2 antibody is apparently not necessary to initiate an immediate hypersensitivity reaction in the guinea pig conjunctiva. The authors also demonstrated that weekly topical application of ovalbumin sensitized guinea pigs for immediate hypersensitivity.

Administration, Topical↗

Surface features of the conjunctiva and cornea.

Guinea pig corneal and conjunctival surfaces were examined by transmission electron microscopy and cytochemistry. Some specimens of cornea and conjunctiva were examined morphologically; others were stained with ruthenium red or tannic acid before examination to enhance the detection of glycoproteins at cell surfaces. The epithelia were covered by microvilli and on the cornea also by microplicae. These surface projections were the shortest (150 nm) over the central cornea, and became progressively longer (approximately 300 nm) over the tarsal and fornical conjunctiva. There was a filamentous cell coat (glycocalyx) on the microvilli and microplicae that was best demonstrated in specimens stained with tannic acid. The glycocalyx extended approximately 300 nm from the tips and lateral surfaces of the microvilli and microplicae. Although there were slight local variations in its thickness, the maximum thickness of the cell coat was uniform over the cornea and conjunctiva. Heavy deposits at the cell surface after ruthenium red staining indicated that the cell coat contained many highly charged polyanions. The density of the ruthenium red stain obscured the fine structure of the filaments in the cell coat. The glycocalyx forms a scaffolding that is believed to bind mucus, with its content of immunoglobulins, by weak chemical interactions to the epithelial surface. Therefore, the microvilli, microplicae, and glycocalyx that were demonstrated in this study provide the structural framework that supports and binds a complex of related factors, including tears, mucus, and immunoglobulins, that have the common function of protecting the eye.

Animals↗

Cell surface variations of the human upper tarsal conjunctiva.

Fifteen specimens of the upper tarsal conjunctiva were obtained from subjects with biomicroscopically normal conjunctivae. Ten specimens were examined by scanning electron microscopy and five by transmission electron microscopy. This examination was performed to examine cells with variant surface morphologic appearance that may be signs of the initial changes typical of those seen in the diseased conjunctiva. Although most specimens had cells with a characteristic uniform distribution of microvilli, seven specimens had cells with nonuniform microvillar patterns. In these seven specimens, less than 5% of the cells showed these changes. Cell surface variations marked by reduced cell diameters and alterations in the microvillar distribution were categorized into two groups: cells with microvilli that were grouped together to form tufts of varying height and number, and cells with a single, centralized group of microvilli. These variations were seen with increased frequency in disease, and it is postulated that the microvillar changes described in this study represent a continuum of adaptive responses of cells to insult and disease.

Conjunctiva↗

[Age-specific features of the vessels of the microcirculatory bed of the conjunctiva].

The microcirculatory bed of various parts of the human bulbar conjunctiva in ontogenesis has been studied in 63 preparations of the eyeball by means of complex morphological methods. Structural peculiarities and functions of all parts of the micro-vessels have been revealed in fetuses, their conjunctiva being not yet subjected to any environmental effect, and in successive age groups of the postnatal development. The period of stabilization and differentiation for all parts of the microcirculatory bed in the eyeball conjunctiva has been stated. Certain age changes of the microcirculatory bed have been revealed in all sectors and in various parts within the sectors; these changes should be taken into account at biomicroscopy and when analysing the data obtained.

Adolescent↗

[Distribution of S-100 protein positive cells in conjunctiva].

We compared the distribution of S-100 protein positive cells in normal conjunctiva and in an induced allergic conjunctivitis model using Hartley strain guinea pigs. The animals were sensitized by intraperitoneal injection of ovoalbumin solution with hydroxy aluminum, followed by topical application of the ovoalbumin solution. The primary antibody was antibovine brain S-100 positive antibody, detected by the avidin biotin complex method. S-100 positive cells were present at the limbal corneal epithelium and on the skin of the palpebrae in both the normal group and the allergic conjunctivitis group, indicating the presence of Langerhans cells. In the allergic group, positive cells were also detected in palpebral conjunctiva and the germinal centers of conjunctival follicles. These cells were identified as follicular dendritic cells or interdigitating cells. In conclusion antigen presenting cells were present in the limbal conjunctiva, follicular and parafollicular area of conjunctival follicles, and palpebral skin in the allergic conjunctivitis models.

Animals↗

[Epithelial-cystic nevus of the conjunctiva (Parinaud's dermo-epithelioma)].

The epithelio-cystic nevus of the conjunctiva, initially improperly denominated by Parinaud dermo-epithelioma, is a dysplasia circumscribed at the level of bulbar conjunctiva, characterized by its forming of epithelial cysts which develop in a base layer made of nevoid cells. This affection evolves by forming epithelial cysts mostly muciparus ones, when the tumor is sited rather far from the limbus, where multiple chaliced cells are to be found in the epithelium, and as simple epithelial cysts, mostly in the epidermis, when it is sited near the limbus where chaliced cells are scarcer. In this condition the setting of the epithelial compound takes the form of full lobules. The nevoid compound represents the capital element which establishes the diagnosis. The epitheliocystic nevus of conjunctiva is a benign dysembryo with excessive development of epithelial cells in a basic layer of nevoid cells. This affection is benign, but its morphologic diversity and its many denominations give rise to periodical debates.

Carcinoma↗

Effect of benzodiazepine on antigen-induced eosinophil infiltration into guinea pig conjunctiva.

The effect of benzodiazepine (BZP) on experimental allergic conjunctivitis was studied. Male Hartley guinea pigs were sensitized with ovalbumin (OVA) and then homologous anti-OVA serum was injected intravenously into guinea pigs for passive sensitization. BZP was administered at a dose of 5 mg/kg by intraperitoneal injection (i.p.) according to the following schedule respectively; a single, repeated twice a day for 3 days, repeated twice a day for 3 days plus a single and repeated twice a day for 7 days. OVA challenge was performed to the conjunctiva, 20 minutes later, conjunctival edema during the early phase response (EPR) was observed and again at 6 hours later, both eosinophil infiltration into the conjunctiva and the platelet activating factor (PAF) serum level during the late phase response (LPR) were examined. BZP did not inhibit the development of conjunctival edema during the EPR. A single dose of BZP did not inhibit, but repeated doses of BZP for 3 or 7 days significantly suppressed eosinophil infiltration during the LPR. And after repeated doses of BZP for 7 days, all PAF serum levels during the LPR were under the lower detection limit of the assay. These results suggest that BZP has an inhibitory effect on antigen-induced eosinophil infiltration into the conjunctiva during the LPR.

Animals↗

Innervation of the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey: a retrograde fluorescent tracing study.

Retrograde fluorescent transport of Fast Blue (FB) and Diamidino Yellow (DY) was used to study the localisation of neurons that innervate the palpebral conjunctiva and the superior tarsal muscle in the cynomolgous monkey. Labelled cell bodies of sensory neurons including a few double labelled cell bodies were found in the ophthalmic part of the ipsilateral trigeminal ganglion. Labelled cell bodies of the sympathetic neurons including a few double labelled cell bodies were located in the middle and cranial part of the ipsilateral superior cervical ganglion, with a few in the contralateral ganglion. Labelled cell bodies of the parasympathetic neurons were all found in the ipsilateral pterygopalatine ganglion and randomly distributed. Neurons were disposed in the opthalmic part of the trigeminal and superior cervical ganglia, whereas parasympathetic neurons were distributed randomly. Cells of the nodose, ciliary, geniculate, otic and first 3 spinal ganglia were unlabelled. Tracing FB and DY from the palpebral conjunctiva and superior tarsal muscle respectively, revealed double labelled neurons in the trigeminal and superior cervical ganglia, probably indicating the presence of collaterals of axons serving both the palpebral conjunctiva and the superior tarsal muscle.

Animals↗

[Immunohistochemical localization of cytosolic sialidase in the epithelium of rat cornea and conjunctiva].

The binding sites of the anti-cytosolic sialidase antibody and Maackia amurensis lectin II (MAL II: specific for sialic acid alpha 2, 3 galactose) in the epithelium of the rat cornea and conjunctiva were immunohistochemically and lectin-histochemically examined, respectively. Cytosolic sialidase was detected in the cytoplasm of the middle and basal epithelium of the cornea and conjunctiva, whereas MAL II bound to the apical region of their epithelium and the mucous of the goblet cells. The predominant action of the cytosolic sialidase, which is stronger than that of the sialyltransferase, may inhibit the terminal sialylation of the glycoconjugates at the middle and basal regions of the epithelium of the cornea and conjunctiva.

Animals↗

Nucleoside transport mechanisms in the pigmented rabbit conjunctiva.

PURPOSE: To elucidate the mechanisms of nucleoside transport in the pigmented rabbit conjunctiva using [3H]uridine as the substrate. METHODS: Excised pigmented rabbit conjunctiva was mounted in a modified Ussing chamber for measurement of short-circuit current (Isc) and [3H]uridine transport. RESULTS: [3H]Uridine transport in the mucosal-to-serosal direction at 10 microM exhibited directionality, temperature dependency, and phlorizin sensitivity. Uridine transport appeared to be mediated via saturable Na(+)-dependent and nitrobenzylthioinosine-insensitive Na(+)-independent processes. The corresponding Michaelis-Menten constants (K(m)) were 1.9 microM and 200 microM, and the maximal uridine fluxes (Jmax) were 29.3 and 46.7 pmol/cm2 per minute. When added to the mucosal side containing 141 mM Na+, uridine increased the Isc in a dose-dependent manner from 0.005 mM to 1.0 mM at 37 degrees C. The K(m) value was 7.6 microM, and the maximal increase in Isc was 0.71 microA/cm2. Hill analysis of uridine transport at 10 microM in the presence of varying Na+ concentrations in the mucosal bathing fluid yielded a Hill coefficient of 1.1, suggesting a 1:1 coupling between Na+ and uridine. Na(+)-dependent uridine transport was inhibited by 10 microM adenosine, guanosine, and inosine, but not by thymidine, suggesting that the transport process may be mainly selective for purine nucleosides. Moreover, 2'-deoxyuridine, 5-iodo-2'-deoxyuridine, and 5-(2-bromovinyl)-2'-deoxyuridine were potent inhibitors of Na(+)-dependent uridine transport. CONCLUSIONS: Na(+)-dependent and Na(+)-independent nucleoside transport processes appeared to be localized on the mucosal aspect of the pigmented rabbit conjunctiva. One or more Na(+)-coupled uridine cotransport processes exhibited a 1:1 stoichiometry and an apparent preference toward purine nucleosides.

Animals↗

Carrier-mediated transport of monocarboxylate drugs in the pigmented rabbit conjunctiva.

PURPOSE: To determine whether an Na+-dependent monocarboxylate transport process exists on the mucosal side of the pigmented rabbit conjunctiva and to evaluate how it may contribute to the absorption of ophthalmic monocarboxylate drugs. METHODS: L-lactate was used as a model substrate. The excised pigmented rabbit conjunctiva was mounted in a modified Ussing chamber for the measurement of short-circuit current (Isc) and 14C-L.-lactate transport. RESULTS: When added to the mucosal side at 37 degrees C and at pH 7.4, applications of as much as 40 mM L- and D-lactate increased Isc in a saturable manner. By contrast, no change in Isc was observed at 4 degrees C or under the mucosal Na+-free condition. 14C-L-lactate transport in the mucosal-to-serosal (m-s) direction at 0.01 mM revealed directionality, temperature dependency, Na+ dependency, and ouabain sensitivity, but not pH dependency. L-lactate transport in the m-s direction consisted of a saturable Na+-dependent process by the transcellular pathway and a nonsaturable process by the paracellular pathway. For the saturable process, the apparent Michaelis-Menten constant was 1.9 mM, the maximum flux was 8.9 nanomoles/cm2 per hour, and the apparent Na+ :L-lactate coupling ratio was 2:1. 14C-L-lactate transport in the m-s direction was significantly inhibited (46% to 83%) by the mucosal presence of various monocarboxylate compounds, but not by dicarboxylate compounds, zwitterionic compound, D-glucose, amino acids, and peptidomimetic antibiotics. Monocarboxylate nonsteroidal anti-inflammatory drugs and the antibacterial fluoroquinolones inhibited 14C-L-lactate transport by 40% to 85%, whereas prostaglandins and cromolyn had no effect. CONCLUSIONS: An Na+-dependent monocarboxylate transport process that may be used by non-steroidal anti-inflammatory and fluoroquinolone antibacterial drugs for transport appears to be present on the mucosal side of the pigmented rabbit conjunctiva. A possible physiologic role for the Na+-dependent monocarboxylate transport process may be to salvage tear lactate.

Animals↗

Malignant melanoma of the conjunctiva with intraocular extension.

Intraocular extension of a malignant melanoma of the conjunctiva is a rare entity. A 75-year-old woman underwent repeated surgery after receiving the diagnosis of a multilocular recurrent malignant melanoma arising from a primary acquired melanosis. Treatment included 2 lamellar sclerokeratectomies and percutaneous radiotherapy. Five years after initial surgery, intraocular extension of the melanoma was observed, and enucleation was performed. Findings from histopathological examination revealed a malignant melanoma occupying part of the ciliary body, the trabecular meshwork, and the iris. Eyes with recurrent malignant melanoma of the conjunctiva should be carefully monitored for intraocular extension. Deep excision of conjunctival melanoma, including lamellar sclerokeratectomy, may abolish the natural barrier against intraocular extension of malignant melanomas of the conjunctiva.

Aged↗