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Histopathology of continuous wave neodymium: yttrium aluminum garnet and diode laser contact transscleral lesions in rabbit ciliary body. A comparative study.

Neodymium: yttrium aluminum garnet (Nd:YAG) laser transscleral cyclophotocoagulation has been shown to be an effective method of lowering intraocular pressure (IOP). Transmission and absorption features of diode laser radiation (810 nm) make these new laser sources suitable for production of transscleral thermal lesions. The transscleral effects on rabbit ciliary body of Nd:YAG and diode laser wavelengths were compared using a CW Nd:YAG laser and a CW Aluminum Gallium Arsenide diode laser. Both lasers were delivered by silica optic fibers, 600 microns in diameter. Eight rabbits were treated by applying the optic fiber 0.5 mm from limbus while increasing energy values from 0.2-2 J. The lesions produced at equal energy values underwent gross and histologic and ultrastructural comparison. Gross examination revealed threshold lesions at 1 J energy for the Nd:YAG laser and 0.8 J for the diode laser. The diode laser produced transscleral thermal lesions of the rabbit ciliary body comparable to those achieved by the Nd:YAG laser. The histologic and ultrastructural study showed that diode laser radiation produced more remarkable damage to the ciliary pigmented structures, causing deep coagulation necrosis of the pigmented epithelium, wide disorganization of the collagen in the stroma, and intravascular coagulation phenomena in the ciliary vessels. Before the introduction of these new laser sources in clinical transscleral procedures, further investigation is needed to determine optimal energy levels.

Animals↗

CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion.

PURPOSE: In a prior study, a S163R mutation in the complement-1q tumor necrosis factor-related protein 5 (CTRP5/ C1QTNF5) was reported to be associated with early-onset long anterior zonules (LAZ) and late-onset retinal degeneration (L-ORD). The ocular tissues involved in the phenotype are the retinal pigment epithelium (RPE) in the posterior segment and ciliary epithelium (CE) and lens in the anterior segment. The purpose of this study was to characterize the spatial and temporal expression of the mouse Ctrp5 gene, determine tissue and subcellular localization, and study the effect of the S163R mutation. METHODS: The expression of the Ctrp5 gene in the mouse was studied by quantitative (q)RT-PCR and in situ hybridization. CTRP5 protein expression and distribution were studied by Western blot analysis, immunohistochemistry, and immunoelectron microscopy. Cellular location of wild-type and mutant CTRP5 in MDCK and COS-7 cells was determined by immunofluorescence and immunoblot analysis. RESULTS: A significant level of Ctrp5 expression was detected in the adult mouse in the ciliary body (CB) and RPE, and expression started at a very early stage of embryogenesis. Immunohistochemical analysis showed CTRP5 protein in the apical processes of the RPE and forming a hexagonal lattice associated with the RPE lateral membranes. In the ciliary body, CTRP5 was localized to the apical aspects of the CE, the region between the bilayered ciliary epithelial cells. The membrane association of CTRP5 in the RPE and CE was further confirmed by immunoelectron microscopy. Furthermore, cultured cells were used to show that the CTRP5 is a secretory protein and that its secretion is impaired by the S163R mutation. CONCLUSIONS: CTRP5, a secretory and membrane-associated protein, is localized to the lateral and apical membranes of the RPE and CB. Impaired secretion of the mutant protein may underlie the pathophysiology of L-ORD and LAZ.

Animals↗

Clinical and pathological status of mesectodermal leiomyoma of the ciliary body. A case report and review of the literature.

The case of a 28-year-old woman with a well-vascularized, yellowish neoplasm in her right eye is reported. The findings upon slit-lamp examination and fluorescein iridography strongly suggested a malignant lesion. The tumor and the adjacent portion of the iris, angle structures, ciliary body, cornea, and sclera were removed en bloc under the half-thickness corneoscleral flap. On the basis of light-microscopic studies, the tumor was suspected to be a neurogenic or glial tumor but further studies confirmed it to be a mesectodermal leiomyoma of the ciliary body. Electron-microscopic studies revealed the smooth muscle nature of the tumor. Because of the high percentage of benign lesions in this site, we believe that even though examinations may suggest malignancy, excision of the tumor should be preferred to enucleation of the globe in cases of ciliary tumor.

Adult↗

Ciliary body in experimental autoimmune uveitis: tissue repair and immunoreactivity of extracellular matrix substances.

Experimental autoimmune uveoretinitis was induced in female Lewis rats with bovine retinal soluble antigen (S-antigen). Tissue changes and immunoreactivities of transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), and extracellular matrix compounds in the anterior segment (ciliary body) were investigated by immunocytochemical methods. Control animals received adjuvant only. The immunized animals were sacrificed at day 0, 3, 7, 14, 20, and 30 postimmunization. Tissue changes that occurred at the peak of inflammation (day 14) included destruction of the inner basement membrane, epithelial cell loss, distortion of the ciliary stroma, and loss of epithelial basal infoldings. Ciliary body architecture was regenerated almost completely by day 30. Basement membrane laminin and collagen type IV levels did not change much during the inflammatory process. Fibronectin labeling level peaked at day 14 postimmunization. Collagen type V level was low at day 14 and elevated at day 20 and day 30. TGF-beta immunoreactivity peaked at day 14 and remained elevated thereafter. EGF labeling did not increase until day 20 and was maximal at day 30. Labeling of both growth factors was principally confinded to the stromal regions. The presence of TGF-beta and EGF in the ciliary stroma at well defined intervals suggests a coordinated effect upon the synthesis and reorganization of the extracellular matrix and possibly upon the inflammatory cell population in the anterior tissue.

Animals↗

Beta-adrenergic receptor subtypes in iris-ciliary body of rabbits.

Direct comparison of drug interaction with intraocular relative to extraocular beta-adrenergic receptors was used to test the hypothesis that the receptors in ocular tissues are of the beta 2-subtype. Potencies for the displacement of 3H-dihydroalprenolol radioligand binding to membranes obtained from rabbit-iris ciliary bodies by beta-adrenoceptor agonists was in the order: isoproterenol greater than or equal to epinephrine greater than salbutamol greater than terbutaline greater than tazolol greater than norepinephrine. Similar radioligand displacement by beta-adrenoceptor antagonists was in the order of potency: alprenolol greater than or equal to bupranolol = oxprenolol = timolol = propranolol greater than ICI 118,551 = IPS 339 much greater than betaxolol greater than metoprolol. Finally, for the above beta-adrenoceptor antagonists, a highly significant correlation was obtained for displacement of radioligand to ocular tissues (pKi values) relative to antagonism (pA2 values) of isoproterenol-induced guinea-pig tracheal relaxation but not guinea-pig atrial chronotropic effects. Consequently, the above three observations reinforce the notion that rabbit-iris ciliary bodies contain beta-adrenergic receptors predominantly of the beta 2-subtype.

Adrenergic beta-Agonists↗

2-Substituted 1, 3, 4-thiadiazole-5-sulfonamides as carbonic anhydrase inhibitors: their effects on the transepithelial potential difference of the isolated rabbit ciliary body and on the intraocular pressure of the living rabbit eye.

In order to understand the pharmacology of carbonic anhydrase inhibitors in reduction of aqueous secretion, three sorts of studies were conducted using five 2-substituted 1, 3, 4-thiadiazole-5-sulfonamides: an inhibition study of carbonic anhydrase II, electrical measurements of the isolated ciliary body, and pharmacological study on intraocular pressure of living animals. The inhibitors of carbonic anhydrase employed here were 2-amino-1, 3, 4-thiadiazole-5-sulfonamide; 2-methylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-formylamino-1, 3, 4-thiadiazole-5-sulfonamide; 2-acetylamino-1, 3, 4-thiadiazole-5-sulfonamide (acetazolamide); and 2-propionylamino-1, 3, 4-thiadiazole-5-sulfonamide. All of these compounds showed significant inhibitory activity to carbonic anhydrase II which exists in the ciliary epithelium, but their potencies of inhibition varied relative to one another (I50S were 1.91 X 10(-7) to 3.3 X 10(-8) M). The effects of the five compounds on electrical phenomena were observed using isolated rabbit ciliary body mounted on an Ussing's chamber. Each compound decreased the negative electrical potential of the tissue (-0.70 mV as the average of the initial values) by 10- to 33%, and this effect was proportional to its inhibitory activity to carbonic anhydrase II. The effects of the five compounds on intraocular pressure were determined, and each compound decreased the intraocular pressure (18 mmHg as the average of the initial values) by 7- to 32%. This effect was also proportional to the inhibitory activity to the enzyme. Correlation between the two effects was studied, and good correlation was observed. This implies that both effects have a common basis which relates to the physiological role of carbonic anhydrase. The present study, therefore, shows the importance of the bicarbonate ion in the aqueous humor formation since it is both substrate and product of carbonic anhydrase II.

Acetazolamide↗

[Intracorneal invasion of the ciliary body by melanoma].

The authors report a case of a slow reduction of vision in the left eye of a 69-year-old woman. The slit-lamp examination of the eye showed a vascularized achromic subconjunctival mass close to the nasal limbus, invading the inferonasal corneal quadrant. At B-scan and standardized A-scan echography, the mass was shown to be localized to the ciliary body, with characteristics of a malignant melanoma. The patient did not want to undergo conservative treatment. Therefore, enucleation was performed and light microscopy revealed a pigmented malignant melanoma of the ciliary body with extrascleral growth and infiltration of the anterior third of the corneal stroma. No alteration of Bowman's membrane was present. The corneal infiltration, limited to the anterior third of the stroma, could be due to the fact that at this level the collagen fibers are disposed less regularly than those of the posterior two-thirds, with this different disposition responsible for the weak resistance opposed to the tumoral invasion.

Aged↗

Early post-operative pressure rise with ciliary body incarceration into Watson type trabeculectomy fistula.

We studied six patients with early failure after Watson's trabeculectomy done due to chronic simple, neovascular, or chronic angle-closure glaucoma. After operation the eyes showed a maximum intraocular pressure (IOP) between 50 mmHg and 66 mmHg and no filtering bleb. Reoperation on the 5th to 14th post-operative day showed incarceration of ciliary body into the trabeculectomy fistula in all cases. The uveal protrusion was replaced and a deep corneoscleral block was removed in front of the scleral spur in three cases, and electrocoagulation of the anterior edges of the trabeculectomy fistula was done in other three cases. After a 4 months to 1.5 years follow-up IOP was 12 mmHg to 18 mmHg and only two eyes needed medical therapy. The results suggest that trabeculectomy in front of the scleral spur is indicated to avoid incarceration of the ciliary body into the trabeculectomy fistula.

Aged↗

[Sympathetic ophthalmia in a case of neurilemmoma of the ciliary body].

The paper presents the case of a 62-year-old male patient, which has been hospitalized with the symptomatology of a acute glaucoma through intumescent lens. After the lens extraction, the globe evolution was to atrophy with chronic irrigation, starting a hypertensive cyclitis at the other eye, assumed to be a sympathetic ophthalmia. After several acute evolutive episodes at both eyes, the enucleation of the primal eye was made and a ciliary body tumour (neurinoma) was discovered. After enucleation under general and local cortisone treatment, the inflammatory phenomena at the sympathetic eye were entering in remission; but the hypertony, which was considered to be an open-angle pre-existent glaucoma, was persistent. The paper also discusses the sympathetic ophthalmia producing mechanism the characteristics of the ciliary body tumour and the diagnosis problems raised by this case.

Ciliary Body↗

Effect of intraocular gamma-interferon on immunoregulatory properties of iris and ciliary body cells.

Resistance of the anterior chamber (AC) of mouse eyes to expression of cell-mediated immunity can be overcome by pre-treating the eye with a dose of recombinant rat gamma-interferon (gamma IFN) that is of itself noninflammatory. To study the mechanism of this form of intraocular inflammation, cells of the tissues surrounding the AC (iris, ciliary body, cornea) were studied in vivo for alterations in phenotype and in vitro regarding their effects on antigen-driven T cell activation. The results indicate that gamma IFN: (1) induced class II major histocompatibility complex (MHC) expression on resident bone marrow-derived cells of iris and ciliary body (I/CB), but not the cornea; (2) led to recruitment of bone marrow-derived cells into the I/CB stroma; and (3) failed to induce class II MHC expression on ocular epithelial cells. Cell suspensions prepared from gamma IFN-treated I/CB superficially resembled normal I/CB cells in that neither were able to activate allogeneic T cells and both were able to suppress antigen-driven T cell activation in vitro. However, unlike cells from normal eyes, I/CB cells from gamma IFN-treated eyes suppressed T cell activation primarily through the secretion of prostaglandins. These results indicate that the ability of gamma IFN-treated eyes to display immunogenic inflammation probably does not result merely from the restoration of conventional antigen presenting cells to this environment, but appears to correlate with a critical change in the molecular mediators of immunosuppression. The findings are discussed in terms of the possibility that the eye may be able to respond to abrogation of its primary immunosuppressive microenvironment by erecting a secondary microenvironment that also is capable of suppressing immunogenic inflammation with a different set of antiinflammatory mediators.

Animals↗

Cytoskeleton in neuroectodermally derived epithelial and muscle cells of the human iris and ciliary body.

The cytoskeleton of epithelial and muscle cells of the human iris and ciliary body was analyzed by immunohistochemistry in three morphologically normal formalin-fixed, paraffin-embedded eyes and in 34 eyes containing a uveal melanoma. Both layers of the iris epithelium reacted with monoclonal antibodies (MAb) V9 and Vim 3B4 to vimentin, whereas the ciliary epithelia additionally reacted with MAb CAM 5.2, CK5, KS-B17.2, and CY-90, recognizing cytokeratins 8 and 18. The same cytokeratin MAb labeled the retinal pigment epithelium, which lacked vimentin. The muscle portion of the anterior iris epithelium, which forms the dilator muscle, as well as the sphincter and ciliary muscles, reacted with MAb DE-U-10 to desmin and 1A4 to alpha-smooth muscle actin. The dilator and ciliary muscles also reacted with V9 and Vim 3B4 to vimentin, and some dilator fibers were weakly immunopositive for cytokeratin 8 and 18 with CY-90 and CAM 5.2. The antigenic profile of iris and ciliary epithelia infiltrated by melanoma cells remained unchanged. The intraocular epithelia, which are developmentally related but differ in function, and the intraocular muscles, which differ in origin but are functionally related, have distinct cytoskeletal profiles and may provide insights into the functional significance of intermediate filament expression.

Adult↗

Surface morphology of the human ciliary body during prenatal development. A scanning electron microscopic study.

The development of the ciliary body was examined by scanning electron microscopy in human embryos and fetuses with a gestation age of 9.5 to 24 weeks. During this period it was possible to follow up the main morphogenetical events, beginning with the appearance of the first radial folds up to the occurrence of ciliary processes with a rather adultlike arrangement. The ciliary processes observed during week 24 differed from those of the adult eye only by their dimensions and the lack of surface infoldings. A primitive pars plana could only be identified during week 24. The morphological basis for aqueous humor production is discussed.

Ciliary Body↗

The sympathetic innervation of the ciliary body and trabecular meshwork of the cat. Fluorescence histochemistry and electron microscopy.

The ciliary body of the cat was investigated by fluorescence histochemistry and electron microscopy in an attempt to clarify its sympathetic innervation. Subconjunctival doses of 5-hydroxydopamine (5-OHDA) or 6-hydroxydopamine (6-OHDA) were given to establish the precise location of the sympathetic nerve terminals. The distribution of noradrenergic fibers and terminals was shown by fluorescence histochemistry to be sparse in the trabecular meshwork and the anterior portion of the ciliary muscle, but dense in the subepithelial tissue. The small and large dense core vesicles which occur in many nerve endings of the subepithelial tissue adjacent to the pigmented epithelial layer increased in electron density following the administration of 5-OHDA. Many degenerating nerve endings were found in the same region of animals treated with 6-OHDA. In contrast, there were few noradrenergic terminals in the ciliary muscle except for a portion of the smooth muscle which was shown to be dually innervated. The noradrenergic fibers in the subepithelial region and the trabecular meshwork may play an important role in aqueous secretion and outflow.

Adrenergic Fibers↗

Type-VI collagen in the human iris and ciliary body.

The distribution of type-VI collagen in the human iris and ciliary body was investigated by means of immunohistochemical techniques and compared with that of type-IV collagen, fibronectin and laminin. As has been described for other tissues, type-VI collagen surrounds type-I and -III collagen fibers. The aggregated form of type-VI collagen (the "long-spacing" or "curly" collagen), which has already been described in the trabecular meshwork and sclera, was also observed at the ciliary muscle tips surrounding the anterior elastic tendons of this muscle. In addition, staining for type-VI collagen was seen directly adjacent to the basement membranes of the ciliary muscle cells, the iris muscles, the uveal vascular endothelia and nerves, but not adjacent to the epithelial basement membranes. The staining did not form a discrete line like the immunoreaction for type-IV collagen, but bundles of marked fibrils extended into the surrounding connective tissue. We assume that type-VI collagen similar to type-VII collagen forms part of an anchoring system for these tissues. As type-VII collagen has been described only in connection with epithelial basement membranes, both type-VI and type-VII collagens may represent anchoring fibrils, however for different tissue components.

Aged↗

Unusual uveal tract tumor: mesectodermal leiomyoma of the ciliary body.

Benign smooth muscle tumor, leiomyoma, can occur throughout the whole body, including the most common sites of the genitourinary and gastrointestinal tracts, less frequently in the skin, and rarely in the deep soft tissue or uveal tract. A 23-year-old Chinese woman presented with a 4 month history of a pigmented ciliary body mass in her left eye. The tumor's clinical appearance and ancillary data were initially consistent with malignant melanoma. However, instead of enucleation, sclerotomy with a tumor biopsy was performed because of the patient's young age and the possibility of benign tumors. Under light microscopy, tumor cells were short spindle- or ovoid-shaped with fine nuclear chromatin and fibrillary cytoplasmic processes resembling neural tissue. Although the tumor displayed neurogenic morphology, it showed strong reactivity for alpha-smooth muscle-specific actin and h-caldesmon, and was negative for neurogenic markers, except CD56, by immunohistochemistry. Primary mesectodermal leiomyoma of the ciliary body was diagnosed because of both the myogenic and neurogenic characteristics. The tumor biopsy or intraoperative frozen section is suggested for accurate pathological diagnosis before enucleation. In a review of the literature, only 14 cases have been reported. Seven cases (50%) were subjected to enucleation and eventually showed a benign mesectodermal leiomyoma. This case report provides novel expression of h-caldesmon and CD56 by the tumor cells of mesectodermal leiomyoma.

Adult↗

Histoautoradiographic and biochemical studies on human and monkey trabecular meshwork and ciliary body in short-term explant culture.

Explants of two types of chamber angle tissue derived from five human autopsy eyes and five freshly enucleated monkey eyes were kept under tissue culture conditions for 1-3 days and then incubated with labelled 14C-glucosamine for 40-48 h. In all specimens an intense labelling was seen histoautoradiographically within the area of the trabecular meshwork, especially in the cribriform layer and the outer wall of Schlemm's canal. Large quantities of silver grains were also found at the tips of the ciliary processes where the nonpigmented epithelium showed the most intense labelling. Measuring the total radioactivity of the two types of specimens in the tissue-localized and the medium-released glycosaminoglycans (GAGs), we found that the type 1 specimens containing only trabecular meshwork work and corneosclera "excrete" relatively more GAGs into the medium than the type 2 specimens consisting of corneosclera, trabecular meshwork and ciliary body. Biochemical analysis of these GAGs revealed that 57%-70% of the tissue GAGs were hyaluronic acid, 16%-33% heparan sulphate and 12%-22% various types of chondroitin sulphate. The findings show that both the ciliary epithelium and the trabecular meshwork possesses the ability to synthesize large amounts of GAGs, probably in the form of proteoglycans. The differences between the in vitro behaviour of type 1 and type 2 specimens indicate a functional interrelationship between the ciliary body and the trabecular meshwork, at least with regard to the GAG metabolism.

Animals↗

Prejunctional prostaglandin receptors in the human iris-ciliary body.

Prostaglandins (PGs) of the E series have been shown to modulate sympathetic neurotransmitter release in a variety of peripheral tissues and organs, including the eye. In this study, we evaluated the inhibitory effects of a series of naturally-occurring and synthetic PGs on field stimulation-evoked release of 3H-norepinephrine (3H-NE) from isolated, superfused segments of human iris-ciliary body. Field-stimulated 3H-NE secretion was calcium-dependent, blocked by selective inhibitors of voltage-sensitive calcium and sodium channels, and originated from a desipramine-sensitive transmitter pool. Evoked 3H-NE release was inhibited in a concentration-dependent manner by PGE2 (EC50 = 45 nM) and several closely related compounds with the following rank order of potency: sulprostone greater than 16,16-dimethyl-PGE2 greater than PGE2 greater than 11-deoxy-PGE1. By contrast, PGF2 alpha was relatively inactive (EC50 greater than 10 microM) in this system. None of the above compounds significantly modified spontaneous 3H-NE efflux. PGE2-mediated inhibition was not antagonized by the selective prostanoid EP1-receptor antagonists AH 6809 (10 microM) or SC-19220 (30 microM), nor did these agents alone affect basal or field-stimulated 3H-NE release. The results suggest that human ocular sympathetic nerves possess inhibitory PG receptors which have the pharmacological properties of the EP3 subtype. These receptors may play a role in local feedback regulation of sympathetic transmission in the iris-ciliary body, and may contribute to symptoms of acute ocular inflammation, including vasodilation, miosis and hypotony.

Adult↗