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Characterization of [3H]forskolin binding sites in the iris-ciliary body of the albino rabbit.

[3H]Forskolin binding sites were identified using membranes prepared from the iris-ciliary body of adult, albino rabbits. Scatchard analysis of saturation binding experiments demonstrated that [3H]forskolin bound to a single population of high affinity sites. The Kd and Bmax values were 8.7 +/- 0.9 nM and 119.0 +/- 30.9 fmol/mg prot. using membranes prepared from frozen tissue and 17.0 +/- 6.2 nM and 184.4 +/- 47.2 fmol/mg prot. using fresh tissue. The binding of [3H]forskolin was magnesium-dependent. The Bmax was enhanced by sodium fluoride and Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog. Forskolin was the most potent inhibitor of [3H]forskolin binding; two commercially-available analogs were weaker inhibitors. In an adenylate cyclase assay, there was the same rank order of potency to enhance enzyme activity. Based upon binding affinities, magnesium-dependence, sensitivity to sodium fluoride and Gpp(NH)p, rank order of potencies of analogs and correlation of binding with adenylate cyclase activity, these studies suggest that the [3H]forskolin binding site in the iris-ciliary body is similar to the binding site in other tissues.

Adenylyl Cyclases↗

Histological and histochemical studies on developing ciliary body in eye of ICR mouse.

Histological and histochemical studies have been made on the microscopic structures of the ciliary body from the developing eyes of both pre- (on day 13, 16 and 18 of gestation) and postnatal (on day 1, 5, 10, 14 and 84) mice of the Jcl:ICR strain and on the acidic glycoconjugates contained in the ciliary body tissues of these animals. As the staining procedures of choice, a hematoxylin-eosin procedure and a sensitized high iron diamine method were employed. A nitrous acid procedure was used in combination for some tissue sections, prior to the sensitized diamine method, to aid in the identification of sulfated glycoconjugates. Both the partes optica and caeca retinae could be identified histochemically as early as day 13 of gestation, whereas these parts could not be histologically distinguished from each other at day 16 of gestation. The ciliary folds were detected first in the external layer at day 16 of gestation and subsequently in the internal layer 2 days later. The heparan sulphate proteoglycan observed not only in the thick basement membrane but also in the intra- and intercellular spaces of the internal layer was localized in a distribution pattern which prevented the occurrence of configurational discrepancies between the epithelial cells lining the layer because of the formation of ciliary folds.

Animals↗

Experimental retinal and ciliary body photocoagulation using a new 670-nm diode laser.

PURPOSE: Evaluation of ocular tissue reactions to 670-nm diode laser. METHODS: Twelve eyes of 12 pigmented rabbits were used. Transscleral contact laser delivery of a new 670-nm diode laser was used to produce retinal laser lesions in four rabbits; endolaser application of this laser produced photocoagulation of the retina in another four rabbits; and ciliary body lesions were produced by transscleral application of this laser in a third group of four rabbits. The rabbits were killed either 2 days or 1, 3, or 6 weeks later; lesions were evaluated by gross examination and histology. RESULTS: The mildest visible retinal lesions were produced by transscleral contact application at 0.2 J (2 seconds, 100 mW); explosive lesions began at 0.6 J. The mildest visible lesions were produced by endolaser application at 50 mW (spot size, 0.5 mm); intensive reactions started to occur at 300 mW, but no explosive lesions were produced below 600 mW. With contact transscleral application, substantial ciliary body reactions occurred at 0.5 and 1.0 J. Histologic examination disclosed destruction of the outer retina, pigment epithelium, and parts of the choroid in mild lesions, and of all retinal layers in the intense lesions. CONCLUSIONS: In this experimental study, the 670-nm diode laser appears to be a promising modality for laser photocoagulation of the retina and ciliary body.

Animals↗

Melanocytoma of the ciliary body.

A 57-year-old Caucasian woman was found, on a routine ophthalmoscopic examination, to have a pigmented ciliary body mass suggestive of a malignant melanoma. The eye was enucleated primarily because a radioactive phosphorus test yielded a 79% greater uptake over the lesion than over a control area-a result regarded as positive at that time. Histopathologically, the lesion proved to be a benign melanocytoma of the ciliary body. Electron microscopy clearly revealed a large complement of inflammatory cells (macrophages) within the tumor. This case reemphasizes the advisability of carefully documenting tumor growth before enucleating eyes harboring pigmented lesions.

Ciliary Body↗

Oral metastasis of ciliary body melanoma. A case report.

Metastases of melanoma rarely occur in the oral cavity, and very few reports have been published. They are chiefly localized in the tonsil, tongue and lip, regardless of the primary site of the neoplasm. A 76-year-old woman presented a brownish berry-shaped floating neoformation at the upper lip, for which she was hospitalized at the Maxillofacial Surgery Unit, Italian Stomatologic Institute, Milan. Medical history revealed that 6 years previously, in 1998, she underwent enucleation of the right eye due to the presence of a melanoma of the ciliary body. The labial neoplasm was removed and at histological examination it was found to be a spindle cell melanoma with numerous melanophages containing granules of melanin. Both the spindle cells and the melanophages were strongly positive for HMB-45 and for S-100. Thus, the presence of melanic neoplasia at an unusual site together with the medical history of melanoma at the ciliary body, removed 6 years previously, indicated a diagnosis of labial metastasis of melanoma of the ciliary body and the patient was therefore transferred to the Oncology Unit for appropriate treatment.

Aged↗

Alpha-2 adrenergic modulation of norepinephrine secretion in the perfused rabbit iris-ciliary body.

Clonidine and other selective alpha-2 adrenergic agonists have been found to lower intraocular pressure in the eyes of rabbits and primates, including humans. It has been suggested that the ocular hypotensive response to alpha-2 agonists may be mediated, in part, by prejunctional inhibition of norepinephrine secretion at intraocular synapses. In this study, we have investigated the effects of adrenergic agonists and antagonists on field-stimulated, Ca++-dependent release of 3H-norepinephrine (3H-NE) from isolated, perfused rabbit iris-ciliary bodies and have utilized radioligand binding methods to identify prejunctional adrenoceptors in this tissue. Clonidine (10(-9)-10(-5) M) produced a dosage-dependent inhibition of stimulation-evoked 3H-NE secretion (EC50 approximately equal to 3 X 10(-8) M), but did not alter basal secretion. Other adrenergic agonists capable of activating alpha-2 adrenoceptors (e.g., epinephrine, norepinephrine and xylazine) also significantly depressed 3H-NE secretion, whereas selective alpha-1 adrenergic or beta adrenergic agonists were without effect. Clonidine-mediated inhibition of 3H-NE release was reversed by the selective alpha-2 antagonist yohimbine (10(-7) M), but was unaffected by prazosin or timolol. Yohimbine alone markedly enhanced 3H-NE secretion, indicating tonic activation of prejunctional alpha-2 adrenoceptors by endogenous released norepinephrine. Forskolin or 8-bromo-cAMP, which alone enhanced norepinephrine secretion, failed to attenuate the inhibitory responses to alpha-2 agonists. 3H-rauwolscine binding measurements showed a small decrease in alpha-2 receptor sites in iris-ciliary body membranes following surgical sympathetic denervation. It is concluded that the rabbit iris-ciliary body contains functional, prejunctional alpha-2 adrenoceptors which may play an autoregulatory role in vivo and contribute to the ocular effects of adrenergic drugs.

Animals↗

Melanocytoma of the ciliary body with scleral extension.

A 35-year-old woman had a circumscribed pigmented scleral lesion overlying a pigmented mass in the ciliary body and trabecular meshwork. Sclerectomy and iridocyclectomy were performed. Histologically, the lesion proved to be a melanocytoma. This represents to our knowledge the fourth reported case of scleral extension of a ciliary body melanocytoma.

Adult↗

[Experiences with a modified, intraocular pressure-reducing excision of the ciliary body].

The treatment of hemorrhagic secondary angle-closure glaucoma following central venous occlusion is generally very difficult. Sautter's ciliary body excision is preceded by two semicircular cyclocryocoagulations performed within 7 days of each other. If IOP remains above 30 mm Hg and the subjective complaints are unchanged, oculopression lasting 10 minutes is performed after local retrobulbar anesthesia. The lowering of pressure thus achieved is sufficient to render a Flieringa ring and paracentesis unnecessary. Several illustrations are included showing the surgical procedure. In 9 cases of hemorrhagic glaucoma following central venous occlusion, there was a further deterioration in vision 8 to 23 months postoperatively. Preoperatively, IOP was between 36 and 63 mm Hg; at late postoperative follow-ups it was between 5 and 30 mm Hg. Complications worth mentioning included three slight losses of vitreous, bleeding into the anterior chamber in four cases, and one loss of the anterior chamber with caput medusae of the iris and secondary opacification of the lens. In 2 cases of aphakic secondary angle-closure glaucoma there was no deterioration in vision and a lowering of pressure to under 30 mm Hg, in spite of 3 preceding intraocular operations. The authors regard the slightly modified ciliary body excision as a possible way of preserving the bulb.

Ciliary Body↗

[Results of the ciliary body exposure (CBE) in secondary angle closure glaucomas. 2. A histological study (author's transl)].

After treatment of secondary angle closure glaucomas by ciliary body exposure with lamellar scleral resection five eyes had to be enucleated. In view of the histological findings taken from these eyes mode of action and therapeutic value of this operation are considered. The effectiveness of scleral resection seems to be doubtful and there is evidence that permanent regulation of intraocular tension depends mainly on direct diathermy of the ciliary body.

Ciliary Body↗

Recurrent medulloepithelioma of the ciliary body. Immunohistochemical characteristics.

A predominantly benign medulloepithelioma of the ciliary body was diagnosed in an 8-year-old girl and resected by iridocyclectomy. It recurred twice during 30 months. Highly malignant histopathologic features developed, and the eye finally perforated and had to be enucleated. No recurrence or metastases have subsequently developed. Histologically, the tumor was a nonteratoid medulloepithelioma consisting of elements resembling embryonic retina, nonpigmented ciliary epithelium, and neuroblasts, but had also areas of obvious glial and neuronal differentiation as judged by immunohistochemistry. The neuroepithelial tumor cells were positive for neuron-specific enolase, vimentin, and often for S-100 protein. The neuroblastic cells were generally positive for neuron-specific enolase and synaptophysin, but were intermixed with glia-like tumor cells positive for vimentin, glial fibrillary acidic protein, and S-100 protein. The results suggest that even a nonteratoid medulloepithelioma may be, unlike retinoblastoma, a truly multipotential tumor.

Child↗

Involvement of p27(KIP1) in proliferation of the retinal pigment epithelium and ciliary body.

According to observations in various cell lines, elimination of the cyclin-dependent kinase inhibitor p27(KIP1) during the late G1 phase of the cell cycle is required for progression to the S phase. Eyes from C57BL/6 mice at embryonic days 13, 14, and 18, and at 4 weeks of age, were analyzed by a bromodeoxyuridine cell proliferation assay and by immunocytochemistry using anti-p27(KIP1) antibody. On embryonic days 14 and 18, p27(KIP1) was detected in the ciliary body. This protein also was detected in the nuclei of the many cells of the retinal pigment epithelium on embryonic day 18, and was present in all such cells at 4 weeks of age. When p27(KIP1)-/- knockout and control mice were injected with bromodeoxyuridine between postnatal days 7 and 10 and analyzed on day 11, positive cells were abundant in the retinal pigment epithelium and the ciliary body of p27(KIP1)-/- mice, whereas few cells were positive in control mice. By fluorescent nuclear staining in whole mounts of retinal pigment epithelium at 12 weeks of age, more nuclei were present in p27(KIP1)-/- than in the wild-type mice. These results suggest that p27(KIP1) was involved in regulation of proliferation in the RPE and the ciliary body.

Animals↗

Localization of lipocalin-type prostaglandin D synthase (beta-trace) in iris, ciliary body, and eye fluids.

PURPOSE: Prostaglandin (PG) D synthase is present in neural tissues and cerebrospinal fluid (beta-trace). This enzyme belongs to the lipocalin family which consists of transporter proteins for lipophilic substances in the extracellular space. PGD synthase is found in retinal pigment epithelium, from where it is secreted into the interphotoreceptor matrix. The authors have undertaken the localization of this unique enzyme within the tissues and spaces of the anterior segment of the eye. METHODS: Iris, ciliary body, lens, and aqueous and vitreous humors were collected from adult rats and mice. PGD synthase activity was determined, and the protein was quantified by Western blot analysis and localized immunohistochemically. Finally, in situ hybridization was performed to localize PGD synthase mRNA. RESULTS: PGD synthase was most abundant in the aqueous and vitreous humors. It was less abundant in tissue cytosolic fractions; these fractions had almost 10-fold as much as their corresponding membrane-bound fractions. Lens tissue had the lowest amount observed. PGD synthase was localized to the epithelial cells of the iris and the ciliary body and to the adjacent extracellular chambers, but PGD synthase mRNA was found only within the epithelial cells. Several glycosylated forms of PGD synthase were also detected. CONCLUSIONS: PGD synthase was synthesized within the epithelial cells of the iris and the ciliary body and was then secreted into the aqueous and vitreous humors, where it accumulated as an active enzyme.

Animals↗

Regional microvascular anatomy of the rabbit ciliary body.

Vascular luminal castings of rabbit eyes were microdissected and studied with the scanning electron microscope to delineate the anatomy of the ciliary body microvasculature. We found regional microvascular differences corresponding to well known gross topographical and ultrastructural differences that may indicate regional functional specialization. The major arterial circle of the iris, derived solely from the long posterior ciliary arteries, supplies the ciliary body via two types of arterioles: anterior and posterior. Spiral iridial process capillaries arise from the anterior (iris) arterioles, are radially arranged along the back of the iris and drain directly into the iris veins. Arterioles from the posterior (ciliary) arterioles enter the head of the process, supplying its tortuous capillaries, some of which drain back into the iris veins. Other capillaries turn posteriorly to form relatively straight, parallel capillaries within the process leaf that drain into the choroidal system via marginal process veins. More posterior arterioles supply capillaries to the base of major processes, to the interprocess ciliary web, and to minor processes. The presence of a dual arteriolar supply to the ciliary processes has also been found in primates and suggests that the rabbit may represent a suitable animal model for the study of factors governing regional ciliary process perfusion.

Animals↗

Biochemical and functional evidence for the presence of dopamine D1 receptors in the bovine ciliary body.

The present paper reports both functional and biochemical evidence for the presence of dopamine D1 receptors in the bovine ciliary body. Dopamine (DA) and dopamine D1 agonists (such as SKF 38,393) but not D2 agonists (such as LY 141,865) produced a concentration-related decrease in the tone induced by a maximally active concentration of carbachol (1 x 10(-4)-5 x 10(-4) M). The maximal relaxation obtained was 100% of the carbachol response using 10(-5) M dopamine or 5 x 10(-6) M SKF 38,393. SCH 23,390, a D1 antagonist, but not (-)-sulpiride, antagonized the effect of DA and SKF 38,393. In accordance with the functional data, radioreceptor binding experiments revealed the existence of a high affinity saturable [3H]SCH 23,390 binding to membranes prepared from ciliary body (Bmax: 344 fmol mg protein-1; Kd: 0.87 nM). The binding was specifically displaced by SCH 23,390, dopamine and dopamine D1 agonists, but not by norepinephrine, D2 agonists, or antagonists such as LY 141,865 and sulpiride. No specific binding was found when using dopamine D2 ligands, such as tritiated spiroperidol.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Orbital extension of Choroidal and ciliary body melanomas.

In a review of 432 choroidal and ciliary body melanomas, histopathologic evidence of orbital extension was found in 45 cases (10.4 percent). The occurrence of orbital extension was influenced mainly by the cell type (P less than .05) and by the size of the choroidal mass (P less than .001). Local orbital recurrence occurred in 23 percent of cases with evidence of extrascleral extension. Survival rates were independent of cell type, pigmentation, and size and shape of the extension. Patients treated by exenteration had significantly better prognosis than nontreated patients or patients treated by chemotherapy, radiotherapy, or local excision (P equals .0002). Early exentration is the best treatment for choroidal melanomas with orbital extension.

Choroid Neoplasms↗

Microcirculation architecture of melanocytic nevi and malignant melanomas of the ciliary body and choroid. A comparative histopathologic and ultrastructural study.

PURPOSE: This study was designed to (1) describe the vascular patterns of ciliary body and choroidal nevi by light microscopy, (2) compare the vascular ultrastructure of nevi with vessels of the normal uvea and uveal melanomas, and (3) compare the behavior of ciliochoroidal melanomas with and without a nevus-like vascular architecture. METHODS: After delineating the vascular patterns of 23 choroidal and ciliary body nevi by light microscopy, the authors identified 49 melanomas that had the same vascular patterns as nevi from a previously published series of 234 uveal melanomas. The survival of these 49 patients who had melanomas with a nevus-like vascular architecture was compared with the 185 patients who had melanomas that lacked this vascular profile. RESULTS: By light microscopy, the only vascular patterns identified in nevi are "normal" vessels, zones of avascularity ("silent" pattern), straight, and parallel vessels; closed vascular loops and networks were not detected in nevi. By transmission electron microscopy, the vascular basement membrane of malignant melanomas was multilaminar, fragmented, and significantly thicker than in normal eyes or nevi. None of the patients with nevi died of metastatic disease. Fourteen percent of patients whose melanomas had the same vascular profile as nevi died of metastatic disease, whereas 32% of patients whose melanomas had vascular patterns other than those seen in nevi died of metastatic melanoma (P = 0.012). CONCLUSIONS: The microcirculation architecture marks tumor progression in uveal melanocytic lesions by light and electron microscopy. In the spectrum of these lesions, nevi are benign, melanomas that have the same vascular profile as nevi have an intermediate biologic behavior, and melanomas with vascular networks are strongly associated with death due to metastatic disease.

Adolescent↗

Prognostic factors in choroidal and ciliary body melanomas.

We reviewed 293 cases of choroidal and ciliary body melanoma with a followup period of five years or more. Nine factors influenced significantly the prognosis: Age of the patient at the time of enucleation, location of the tumor and of its anterior border, largest tumor diameter in contact with the sclera, height of the tumor, integrity of the Bruch membrane, cell type, pigmentation, and scleral infiltration by tumor cells. Some of these factors can be evaluated clinically before the enucleation. Seven sets of three factors each were determined in order to have better prognostic values based on the clinical data and the cell type. The largest tumor diameter is the single most important clinical and pathological prognostic factor. The prognosis is relatively good when this diameter is 10 mm or less and becomes poor when it exceeds 10mm.

Adolescent↗

Endogenous catecholamine concentrations in rat iris-ciliary body.

Endogenous catecholamine concentrations in the rat iris-ciliary body (ICB) were determined using the technique of microwave irradiation, whereby enzymes are inactivated within milliseconds, and high performance liquid chromatography. Rats were sacrificed by microwave irradiation at 9.5 kW at 2450 MHz for 0.9 seconds. The eyes were enucleated, the ICBs isolated, and 10 ICBs from 10 eyes were treated as one sample. Endogenous norepinephrine levels in the rat ICB were 19.5 +/- 2.3 nmol per gram tissue protein (mean +/- SE, 7 samples), while endogenous dopamine levels were 3.2 +/- 0.2 nmol. Epinephrine could not be detected. A single instillation of 5 microliters of 0.05% apraclonidine, an alpha-2 agonist, in one eye of an animal raised the NE level in the ICB of the treated eye by 8% compared to that in the untreated fellow eye (P < 0.05).

Adrenergic alpha-Agonists↗