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Totally necrotic choroidal and ciliary body melanomas: associations with prognosis, episcleritis, and scleritis.

PURPOSE: To report associations between prognosis, total tumor necrosis, scleritis, and episcleritis in choroidal and ciliary body melanomas. METHODS: In this retrospective observational histopathologic study, 157 totally necrotic melanomas and 177 melanomas that were not totally necrotic of choroidal and ciliary body were retrieved from the Registry of Ophthalmic Pathology. The eyes were examined for the histologic evidence of inflammatory cells within the sclera and episcleral tissues. Contingency table, Kaplan-Meier, and Cox proportional hazard regression analyses were performed. In the survival analyses, only deaths with metastatic melanoma were considered as events in the statistical analysis. RESULTS: Among the totally necrotic melanomas, 118 of 157 (75.1%) had both episcleritis and scleritis; two of 157 (1.3%) had scleritis only; 29 of 157 (18.5%) had episcleritis only; and eight of 157 (5.1%) had neither episcleritis nor scleritis. Among the non-necrotic melanomas, 23 of 177 (12.9%) had both episcleritis and scleritis; eight of 177 (4.5%) had scleritis only; 71 of 177 (40.1%) had episcleritis only; and 75 of 177 (42.3%) had neither episcleritis nor scleritis. Cox regression indicated that total necrosis and scleritis were prognostically significant (P <.05) when analyzed univariately but not significant when analyzed multivariately with tumor size. CONCLUSIONS: Scleritis and episcleritis were statistically significantly associated with total tumor necrosis. There was a higher incidence of episcleritis than scleritis in both the necrotic and non-necrotic tumor types. Associations with patient outcome were identified for necrosis and scleritis. However, these associations were statistically insignificant when the prognostic effect of tumor size was also considered in a multivariate model.

Choroid Neoplasms↗

Direct demonstration of dopamine D1-like receptor sites in the ciliary body of the rabbit eye by light microscope autoradiography.

The pharmacological characteristics and the anatomical localization of [3H]-SCH 23390 in sections of the ciliary body of the rabbit eye were analyzed using a radioreceptor assay and autoradiographic techniques. [3H]-SCH 23390 was bound to sections of rabbit ciliary body in a manner consistent with the labelling of D1-like receptor sites. The dissociation constant (Kd) was 0.62 nmol/l, while the maximum binding capacity (Bmax) was 117 +/- 9 fmol/mg tissue. Light microscope autoradiography revealed [3H]-SCH 23390 binding sites within the epithelium of the ciliary processes, which is the ocular structure involved in the secretion of aqueous humor. No specific accumulation of silver grains was noticeable within the iridocorneal angle, which is the structure involved in the outflow of aqueous humor. These findings suggest that the rise in intraocular pressure caused by D1 receptor agonists is probably mediated by an increase of aqueous humor formation rather than by an inhibition of the outflow of aqueous humor.

Animals↗

Leiomyoma of the ciliary body. Report of 2 cases.

PURPOSE AND METHODS: The files of the Eye Pathology Institute contain only two cases of leiomyoma of the ciliary body. The diagnoses were re-evaluated, applying modern immunostainings. RESULTS: The tumors were composed of interlacing fascicles of spindle-shaped cells with bright eosinophilic cytoplasm and cigar-shaped nuclei. Both tumors were well-vascularized, mostly by thin, branching capillaries. Larger vessels were also seen. In one case the tumor perforated the sclera. The tumor cells reacted with the reticulum stain and the Masson trichrome and were positive for antibodies against: smooth muscle actin (SMA), muscle specific actin (MSA), laminin and vimentin (one case). CONCLUSION: Leiomyoma of the ciliary body is a rare smooth muscle cell tumor that may arise from either pericytes, ciliary - or intrascleral heterotopic muscle.

Actins↗

Differential diagnosis of anterior chamber cysts with ultrasound biomicroscopy: ciliary body medulloepithelioma.

PURPOSE: To describe a case with motile cyst in the anterior chamber in the right eye of a 7-year-old boy. METHODS: The right eye's visual acuity was 20/50. Intraocular pressure was 59 mmHg. Slit-lamp examination showed prominent rubeosis iridis and a grey-white mass floating freely in the anterior chamber. Ultrasound biomicroscopy revealed a cystic mass in the anterior chamber. A diagnostic cyclectomy with removal of the anterior chamber cyst was performed. Histopathology of the anterior chamber lesion showed an intact cyst composed of medullary epithelial cells. Medulloepithelioma with malignant criteria was diagnosed and the eye was enucleated. RESULTS: Pathology demonstrated an medulloepithelioma with a few mitotic figures and nuclear pleomorphisms within the ciliary body. The patient was followed for 8 months without any metastasis in the orbit or elsewhere. CONCLUSION: Intraocular medulloepithelioma is a rare embryonic benign or malignant neoplasm typically diagnosed in the first decade of life as a ciliary body mass. A dislodged, free-floating anterior chamber cyst associated with neovascular glaucoma is typical of medulloepithelioma in children. This unique presentation should be differentiated from congenital iris epithelial, post-traumatic, epithelial, parasitic and neoplastic cysts. Ultrasound biomicroscopy is useful for analysing the structure of the anterior segment mass. Ciliary body medulloepithelioma is characterized by echogenic mass heterogeneity and an irregular surface containing multiple cystic cavities. Lack of glial differentiation may predict a better clinical outcome in primary neuroectodermal brain tumours.

Anterior Chamber↗

Swelling activates chloride current and increases internal calcium in nonpigmented epithelial cells from the rabbit ciliary body.

Membrane current and [Ca]i in rabbit nonpigmented ciliary body epithelial cells (NPE cells) were monitored with combined patch-clamp and fura-2 measurements during cell swelling induced by anisosmotic conditions. In the presence of K-channel blockers, cell swelling produced an increase in membrane current, accompanied by an increase in [Ca]i. Structural changes in the cell, associated with membrane deformation, may be the cause of the increase in [Ca]i during swelling. The conductance activated by swelling was permeable to Cl: it was dependent on the Cl concentration gradient across the cell membrane, and it was blocked by the Cl-channel blockers DIDS, SITS, NPPB, and DIOA. Although swelling increased both Cl current and [Ca]i, there was no evidence that Ca was involved in the regulation of the Cl conductance. Cell swelling activated the current even when [Ca]i was strongly buffered at an elevated level (500 nM) or at a low level (approximately 0) with internal Ca-BAPTA/Cs-BAPTA mixtures. In addition, Cl conductance was unaffected when [Ca]i was increased with a Ca ionophore. There was also no evidence that cAMP participates in the regulation of the Cl conductance: swelling activation of the current occurred in the presence of cAMP inhibitor (Rp-cAMP-S) and cAMP mimic (Sp-cAMP-S). The data suggest independent involvement of Cl conductance and internal Ca in the regulation of cell volume in NPE cells.

Animals↗

Comparative studies on fatty acid composition and phospholipases A2 and C activities in rabbit and bovine iris-ciliary body.

It is well established that production of prostaglandins by ocular tissues is dependent upon the species. The rabbit iris-ciliary body produces greater amounts of prostaglandins than that of the bovine. To throw more light on the biochemical basis underlying these differences we have compared the fatty acid composition and phospholipases A2 and C activities in rabbit and bovine irides. When the concentration of arachidonic acid is expressed as % of total fatty acids, phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, separated from rabbit iris phospholipids, contained 56, 38 and 18% more arachidonic acid, respectively, than those of the bovine. The total lipid phosphorus in rabbit and bovine iris-ciliary body were found to be 13.74 and 9.34 mumol g-1 wet tissue, respectively. Subcellular fractions, prepared from rabbit iris, contained 30-230% more phospholipase C activity than those of the bovine, and about 5-41 times higher phospholipase A2 activity than those of the bovine. In the rabbit iris microsomal fraction, phospholipase C activity is 33 times higher than that of phospholipase A2. However, the data presented suggest that phospholipase A2, rather than phospholipase C, is the enzyme which is more involved in arachidonic acid release for eicosanoid biosynthesis. These findings suggest that the high contents of arachidonic acid and phospholipases A2 and C in the rabbit iris could contribute to its unique capacity to synthesize and release prostaglandins in the anterior segment as compared to that of other mammalian species.

Animals↗

Stimulatory effects of prostaglandin D2 analogues on adenylate cyclase in rabbit iris-ciliary body membrane fractions.

Effects of prostaglandin (PG) D2 analogues on the adenylate cyclase activity in membrane fractions of the iris-ciliary body complex were studied. PGD2 dose-dependently activated the adenylate cyclase with a maximal activity increase of about 60%. The concentration required to cause a half-maximal stimulation (EC50) was about 5 x 10(-7) M. The stimulatory effect of PGD2 was totally dependent on GTP with EC50 for GTP at about 10(-7) M. The rank order of potency of PGD2 analogues for stimulating the adenylate cyclase and BW245C (a selective PGD2 agonist) greater than PGD3 greater than PGD2 greater than 9 beta-PGD2. PGD2 metabolites and PGD2 analogues which have little hypotensive activity were essentially ineffective in stimulating the adenylate cyclase. This rank order was strikingly similar to that reported previously for their intraocular pressure-lowering effects. One exception was PGD2 methylester. This compound, though reportedly effective in reducing IOP, failed to activate the adenylate cyclase by itself, presumably because its hypotensive effect is due to its hydrolyzed product, PGD2. These results indicate that the abilities of PGD2 analogues to stimulate the adenylate cyclase of the iris-ciliary body complex in GTP-dependent manner are highly correlated with their ocular hypotensive activities, and suggest that a PGD2 receptor-stimulatory GTP-binding protein-adenylate cyclase complex is involved in the PGD2-induced ocular hypotension.

Adenylyl Cyclases↗

The tight junctions of rabbit choroid plexus and ciliary body epithelia. A comparative study using the double replica freeze-fracture technique.

The spatial arrangement of tight junctions in choroid plexus and ciliary body rabbit epithelia has been determined by studying freeze-fracture complementary replicas. In the choroid plexus epithelium, the interruptions of the junctional P-face fibrils were measured to be 14% in their total length. In the ciliary body epithelium, where the fibrils were found to be more fragmented than in the choroid plexus, the P-face fibril interruption accounted for 12% of the total length of the zonulae occludentes sealing the non-pigmented cells and 30% in the focal linear tight junctions connecting the non-pigmented cells at their apices. In both epithelia, the interruptions of the ridges are precisely complemented by particles or short bars of similar length found in the E-face furrows. Consequently, it is possible to conclude that the junctional fibrils are continuous in these two epithelia. For the zonulae occludentes, this continuity appears to be inconsistent with the 'leaky' properties of these epithelia shown by some physiological investigations.

Animals↗

Synergistic increase in Ca2+ produced by A1 adenosine and muscarinic receptor activation via a pertussis-toxin-sensitive pathway in epithelial cells of the rabbit ciliary body.

The combined effects of adenosine and acetylcholine on the intracellular free-Ca2+ concentration in nonpigmented epithelial cells of the rabbit ciliary body were investigated using fura-2 fluorescence-ratio imaging. Acetylcholine (10 microM) by itself produced a modest increase in [Ca2+]i. Acetylcholine in combination with adenosine, or with the A1-specific agonists N6-cyclohexyl-adenosine, N6-cyclopentyl-adenosine and (R)-N6-(2-phenyl-1-methylethyl)-adenosine (0.1-1 microM), induced a massive increase in [Ca2+]i, which could be blocked by the A1-specific antagonist 8-cyclopentyl-1,3-dipropylxanthine. However, the A2-specific agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamide-ade nos ine and the antagonist 3,7-dimethyl-1-(2-propynyl)xanthine were without effect. Incubation of the tissue with pertussis toxin did not alter the response to ACh alone but eliminated the synergistic effect of adenosine (or of epinephrine). It was concluded that in the epithelial cells of the rabbit ciliary body, adenosine and epinephrine synergistically potentiate the rise in [Ca2+]i produced by ACh. This potentiation appears to occur via a pertussis-toxin-sensitive pathway, perhaps through G(i).

Acetylcholine↗

Characterization of alpha 2-adrenoceptor subtypes in the porcine eye: identification of alpha 2A-adrenoceptors in the choroid, ciliary body and iris, and alpha 2A- and alpha 2C-adrenoceptors in the retina.

The subtypes of alpha 2-adrenoceptor were characterized in the choroid, ciliary body, iris and retina of the pig eye by using radioligand binding. [3H]-MK912 labelled dense populations of alpha 2A-adrenoceptors in the choroid and ciliary body. In the retina, [3H]-MK912 labelled both alpha 2A- and alpha 2C-adrenoceptors. In the iris, receptors of the alpha 2A-adrenoceptor type were detected by using either [3H]-MK912 or [3H]-RX821002 as radioligands.

Animals↗

Hamartomatous adenoma of the nonpigmented ciliary epithelium arising in iris-ciliary body coloboma. Light and electron microscopic observations.

A 2 1/2-year-old boy had a slowly enlarging mass at the site of a typical iris-ciliary body coloboma for 2 years. The mass was excised partially by iridocyclectomy. By light microscopy, the tumor cells were embedded in a rich mucoid stroma that contained abundant hyaluronidase-sensitive acid mucopolysaccharides. By electron microscopy the tumor showed light and dark cells with interdigitating cell membranes, desmosomes, gap junctions, multilaminar basement membrane, and numerous extracellular collagen fibrils that resembled vitreous fibrils. We believe that the tumor represents a hamartomatous (congenital) adenoma of the nonpigmented ciliary epithelium rather than a conventional (acquired) adenoma, since it developed precisely within a colobomatous defect of the iris and ciliary body.

Adenoma↗

Retinal detachment due to breaks in pars plicata of ciliary body after endogenous fungal endophthalmitis.

An eye with retinal detachment due to breaks in the nonpigmented epithelium in the pars plicata of the ciliary body was reported in a patient who had been infected by endogenous Candida endophthalmitis about 3 years previously. He had no history of ocular trauma or atopic dermatitis, and had undergone extracapsular cataract extraction because of secondary cataract following the endophthalmitis. Three months later, the breaks were detected in his right eye, distributed extensively between the 3:30 and 11:45 o'clock meridians in the pars plicata. The posterior edges of these breaks were pulled to the contracted posterior capsule by zonular fibers. Posterior capsulectomy, vitrectomy, encircling and scleral buckling were performed and resulted in the reattachment of the retina. It was suggested that the ciliary body which had been damaged by endophthalmitis played a role in the development of these breaks.

Candidiasis↗

Malignant melanoma of the choroid and the ciliary body 1956-1975 in Halland and Gothenburg. Incidence, histopathology and prognosis.

All the 91 cases of enucleated malignant melanoma of the choroid and ciliary body in an area of the Swedish west coast (630 000 inhabitants) during the period 1956-1975 are analysed. The incidence was 0.72/100 000 inhabitants and year, which means that there was no increase lately corresponding to the increase described for cutaneous melanoma. Distribution according to age, sex and cell-type corresponded to other materials. 86 tumours were choroidal, 5 were located in the ciliary body. The mortality after 15 years was 50%. Tumours of the epitheloid type showed a surprisingly low mortality (29%). In only one case, with a 10 years survival, metastases were found at the time of primary diagnosis. The possibilities for early detection of metastases were, however, small. In 11 cases a period of delay and/or other treatment had preceded enucleation. The prognosis for these cases was not worse than for those who underwent immediate enucleation.

Adult↗

[3H]ouabain localization of Na-K ATPase in the epithelium of rabbit ciliary body pars plicata.

The secretion of the aqueous humor has been proposed to occur as the result of active Na+ transport by a ouabain-sensitive Na-K ATPase. We have examined the localization of this enzyme in the epithelium of rabbit ciliary body pars plicata using [3H]ouabain autoradiography. Single ciliary processes were isolated and incubated in Ringer containing [3H]ouabain. Processes were then rapidly frozen, freezedried, sectioned and exposed for autoradiography. In the light microscope, silver grains were found predominantly over the nonpigmented epithelial cells. In the electron microscope, grains could be localized for the most part to the interdigitations of the nonpigmented cell basolateral membrane. Label could also be observed at a much lower density above other membranes and above the pigmented and nonpigmented cell cytoplasm. No label was found in sections of control tissue which had been incubated in [3H]ouabain with an excess of cold ouabain. To show that the [3H]ouabain had free access to all of the membrane surfaces within the epithelium, in parallel experiments we incubated isolated processes in horseradish peroxidase. Our experiments suggest that most of the active Na+ transport in ciliary body epithelium occurs across the basolateral membrane of nonpigmented cells into the posterior chamber. Furthermore, the placement of the Na-K ATPase within the narrow membrane infoldings of the interdigitations is consistent with a role for this enzyme in water transport and the production of the aqueous.

Animals↗

[Variation of inflammatory reaction of ciliary body--harmony between clinic and basic science].

Histopathological findings of ciliary epithelium and muscle were discussed in the inflammatory conditions that are induced in endophthalmitis, blood-aqueous barrier destruction, cyclocryotherapy and cyclophotocoagulation. The clinical results were also discussed regarding the reduction of aqueous production and uveoscleroplasty which are introduced by the experimental cyclophotocoagulation at the pars plicata/pars plana. Tissue destruction by inflammatory reaction occurred in not only the ciliary body but also in the retina if the endophthalmitis had progressed to the point of severity. The post-inflammatory reactive hypertrophy of nonpigmented and pigmented ciliary epithelium was mild at pars plicata and the anterior portion of the pars plana. On the other hand, it was severe at the posterior portion of the pars plana and the ora serrata, and it was clear that the cyclitic membrane developed into proliferative vitreoretinopathy. Adult pig cultured nonpigmented ciliary epithelium showed proliferated tissue resembling the cyclitic membrane. These results show that nonpigmented ciliary epithelium has a strong proliferative activity as much the same as fibroblasts. The destruction of the blood-aqueous barrier was produced by corneal perforation, paracentesis, prostaglandin E1 (PGE1) subconjunctival injection, and hyperosmotic agent intraophthalmic artery injection. The localization of the tissue destruction was made clear at the beginning portion of the ciliary process and the posterior part of the pars plana. The repetitive instillation of latanoprost and cyclosporin A eye drops showed the same localization of the tissue damage. These results suggest that the beginning portion of the ciliary process is vulnerable to inflammatory agents. Cyclosporin A might produce a toxic reaction on nonpigmented ciliary epithelium, and latanoprost destroys the blood-aqueous barrier. Cyclocryotherapy produces severe necrosis of the pigmented ciliary epithelium and melanocytes, and atrophy of pigmented ciliary epithelium and ciliary muscle, and the proliferation of nonpigmented ciliary epithelium follows. Because cyclocryotherapy is a blind therapy, hypotony and phthisis bulbi will occur if the pars plicata is damaged severely, and the intraocular pressure (IOP) decrease will not be achieved if pars plana is damaged locally. Finally, we demonstrated that it is difficult to predict the therapeutic outcome of cyclocryotherapy. Cyclophotocoagulation of the pars plicata and the pars plana produced severe necrosis of pigmented ciliary epithelium and melanocytes, and atrophy of pigmented ciliary epithelium and ciliary muscle, and the proliferation of nonpigmented ciliary epithelium followed. Cyclitic membrane was developed from the proliferation of nonpigmented ciliary epithelium depending on the severity of photocoagulation. From these experiments the complete destruction of the pars plicata might result in for hypotony and phthisis bulbi. The reduction of aqueous production for angle-closure glaucoma was achieved by moderate cyclophotocoagulation of the pars plicata. On the other hand, moderate cyclophotocoagulation of the pars plicata for open-angle glaucoma produced the obstruction of uveoscleral aqueous outflow which compensated for the reduction of aqueous production. From these results we suggested that moderate cyclophotocoagulation of the pars plana for open-angle glaucoma might be necessary to effect the increase of uveoscleral aqueous outflow. Moderate and severe cyclophotocoagulation of the transit area between the pars plicata and the pars plana might bring about reduction of aqueous production and the increase of uveoscleral aqueous outflow.

Animals↗

The ciliary body and the suspension of the lens in a monkey (Cercopithecus aethiops). A scanning electron microscopic study.

The zonules of Zinn and their insertion on the ciliary body and the lens in a monkey (Cercopithecus aethiops) have been studied with the scanning electron microscope. The specimens were dissected after drying by the critical point method, and the lens was separated from the ciliary body by simple traction. The pars plana was completely covered by a mat which consisted of meridionally directed zonule-like fibers. Most of these fibers inserted at the base of the posterior end of the ciliary processes, and some of them radiated into the valleys between the processes. About two fibers for each process split off from the mat and became attached to the sides of the processes near their posterior ends. The true zonules spanned from the sides of the processes to the pre- and post-equatorial region of the lens. They were clearly separated into an anterior and a posterior row with no fibers crossing over from one row to the other. Usually four true zonules joined each process, i.e. one zonule of the anterior row and one of the posterior row attached to each side of the single ciliary process.

Animals↗

Effects of calcium channel antagonists on the depolarization-evoked release of norepinephrine in the rabbit iris-ciliary body.

The effects of several representative calcium channel antagonists on depolarization-evoked release of [3H]-norepinephrine were investigated in isolated, superfused rabbit iris-ciliary bodies. Potassium (50 mM)-evoked neurosecretion was blocked by 5 mM CoCl2 and partially inhibited by 10(-6) M nitrendipine or verapamil. Electrically-evoked neurosecretion was similarly blocked by CoCl2, but was unaffected by nitrendipine or verapamil. It is concluded from these results that sympathetic terminals in the rabbit iris-ciliary body contain dihydropyridine- and verapamil-sensitive calcium channels which contribute, under conditions of prolonged depolarization, to neurotransmitter release.

Action Potentials↗

High glucose-6-phosphatase activity in non-pigmented epithelial cells of rabbit ciliary body.

For study of the origin of glucose in the aqueous humor, glucose-6-phosphatase (G6Pase) and hexokinase activities, and glycogen, were cytochemically examined in the ciliary body (CB) of rabbit. G6Pase activity was also assayed biochemically. The staining reaction for G6Pase activity was strong in the non-pigmented epithelium (NPE) in the pars plana and tips of ciliary processes in the region containing large ciliary pockets within the pars plicata. NPE cells contained abundant reaction product for G6Pase activity in the endoplasmic reticulum (ER) and nuclear envelope. However, NPE in other regions of the CB and pigmented epithelium (PE) of CB, and other areas surrounding the anterior and (PE) of CB, and other areas surrounding the anterior and posterior chambers, showed weak or no G6Pase staining reaction. Biochemical G6Pase activity in the whole ciliary body was relatively high. Both NPE and PE in the pars plana and the tips showed strong staining reaction for hexokinase activity but no staining for glycogen. Furthermore, NPE cells in the tips bore large aggregates of smooth ER and many Golgi apparati. These suggest that the high G6Pase activity in NPE cells in the pars plana and the tips is related to glucose release into the aqueous humor.

Animals↗