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PubMed2005

Medulloepithelioma of the ciliary body and optic nerve: clinicopathologic, CT, and MR imaging features.

The definitive diagnosis of medulloepitheliomas of the ciliary body and optic nerve is made by histopathologic examination. Familiarity with rare tumors aids clinicians in accurately diagnosing this rare neoplasm. CT and MR imaging findings can be helpful, especially if the mass is confined in an area of the ciliary body without involvement of the retina. The characteristic findings of cystic changes and possible calcification are suggestive of medulloepithelioma rather than melanoma. The more common and ominous retinoblastoma shares some radiologic features with medulloepithelioma, however, and is thus often a consideration. Clinical diagnosis of medulloepitheliomas of the optic nerve and central nervous system (CNS) is more challenging. The diagnosis is often made by histopathologic examination. Lastly, coexisting CNS tumors and anomalies have been reported in association with intraocular medulloepitheliomas and should be recognized.

Ciliary Body↗
PubMed1998

Development of the avian iris and ciliary body: mechanisms of cellular differentiation during the smooth-to-striated muscle transition.

The avian iris and ciliary body undergoes a transition from smooth-to-striated muscle during embryonic development. Using antibodies specific for smooth muscle-specific alpha-actin and myosin heavy chain, we confirm that a smooth-to-striated muscle transition occurs between E8 and E17 in both iris and ciliary body of the chick. To study the mechanisms regulating the transition in muscle type, we analyzed the fate of quail clones derived from E7 iris cells. When cells were cloned alone, 45/71 colonies differentiated into smooth muscle and 10/71 became striated muscle. None of the colonies were mixed with respect to muscle phenotype, indicating a lack of pluripotent stem cells. Furthermore, clones giving rise to nonstriated muscle could not be forced to incorporate into myotubes when cocultured with chick myocytes. Clones grown in coculture with chick embryo fibroblasts or E11 iris cells had very high cloning efficiencies (>98%). Significantly more clones differentiated into striated muscle when cocultured with E11 cells (60/156) than when cocultured with fibroblasts (29/108). This was due to an increased recruitment of undifferentiated cells into striated muscle, rather than a change in the percentage of cells differentiating into smooth muscle. In vivo and in vitro, various smooth and striated muscle-specific markers including contractile proteins, acetylcholine receptor subtypes, and transcription factors were colocalized in cells. Although our data argue against a multipotent stem cell for smooth and striated muscle cells, they cannot exclude a role for transdifferentiation. Cumulatively these results suggest that both smooth muscle and migratory myoblasts contribute to the development of myotubes in the avian iris and that this process is regulated in a non-cell-autonomous fashion by locally generated signals.

Acetylcholine↗
PubMed2002

Renin-angiotensin system expression and secretory function in cultured human ciliary body non-pigmented epithelium.

BACKGROUND: Renin-angiotensin system (RAS) components have been identified in human ciliary body and aqueous humour, pointing to a role for the RAS in the regulation of aqueous humour dynamics. Here, the authors examine the functional expression of a RAS and the effects of angiotensin II (AII) on a signal transduction pathway and ion secretion mechanism in cultured human ciliary body non-pigmented epithelium (HNPE). METHODS: RAS expression was examined in cultured HNPE cells using polymerase chain reaction (PCR) analysis. Secretory function was determined using spectrofluorescence imaging microscopy to measure cell calcium (Ca(2+)(I)) and volume responses. Single channel patch clamp techniques were employed to investigate ion channel activity. RESULTS: PCR analysis demonstrated the expression of angiotensinogen and the AT(1b) receptor in HNPE cells. A large conductance potassium (BK) channel (mean 190 (SEM 5.6) pS, n = 22 cells), was observed in plasma membrane patches. This channel was calcium sensitive with channel open probability (Po) increasing with increasing Ca(2+)(I) (K(0.5) 10.79 (0.44) microM Ca(2+), Hill coefficient of 1.04 (0.04)). AII (100 nM) increased the number (N) of active BK channels in HNPE cells and also the probability of channel opening (Po). N.P(o) increased from 0.008 (0.002) to 1.38 (0.4) following the addition of AII (p=0.0064). AII also induced a rapid rise in Ca(2+)(I) from resting values of 112 (14) nM to a peak of 992 (106) nM (p<10(-4)). A simultaneous cell volume reduction of 24.70% (3.34%) (p<10(-4)) occurred during this calcium signal. Losartan (1 microM) significantly blocked the AII induced BK channel activation (p=0.0131), the Ca(2+)(I) response (p<10(-4)), and the AII induced volume effect (p=0.0046). CONCLUSION: It was demonstrated that AII activates a Ca(2+)(I) signalling system which subsequently increases potassium ion channel activity. These effects are accompanied simultaneously by cell volume loss, indicating that AII acts as receptor operated secretagogue in HNPE cells. The ability of an AT(1) receptor antagonist to inhibit these processes may thus offer a new family of pharmaceutical agents to the current armamentarium in the treatment of glaucoma.

Angiotensin II↗
PubMed1998

Development of the avian iris and ciliary body: the role of activin and follistatin in coordination of the smooth-to-striated muscle transition.

Although general principles have been established in the regulation of vetebrate organogenesis, the specific molecules responsible for such signaling are just being identified. We have studied differentiation in the avian iris and ciliary body which undergoes a transition from smooth to striated muscle. Using heterochronic cocultures, we have found that striated muscle differentiation in pretransition (E8) cells is induced by midtransition (E11) cells through a secreted and soluble activity. In addition, contact-mediated mechanisms among pretransition cells prevented precocious striated muscle differentiation. We have tested the role of activin and its antagonist follistatin, as candidate regulators of this muscle transition. Activin induced smooth muscle differentiation while repressing striated muscle development. Conversely, follistatin promoted the emergence of striated muscle, while inhibiting smooth muscle differentiation. Significantly, secreted follistatin activity was found to increase during the smooth-to-striated muscle transition. Moreover, the striated muscle inducing activity from midtransition iris and ciliary body cell conditioned medium was depleted with an activin-affinity column which binds follistatin. These results suggest that activin and follistatin coordinate differentiation in the avian iris and ciliary body.

Activins↗
PubMed2005

Tumor, node, metastasis classification of malignant ciliary body and choroidal melanoma evaluation of the 6th edition and future directions.

PURPOSE: The tumor, node, metastasis classification of malignant uveal melanoma has been revised. We evaluated how the 6th edition (TNM6) improves on the previous one (TNM5). DESIGN: Population-based, retrospective, cross-sectional study. PARTICIPANTS: Two hundred eighty-nine consecutive patients who had a ciliary body and choroidal melanoma treated in the district of the Helsinki University Central Hospital, Finland, between 1962 and 1981. METHODS: Tumor dimensions, ciliary body involvement, and extraocular extension were evaluated from histopathologic sections and pathology reports. Tumors were assigned into categories and stages according to TNM6, TNM5, and 2 previously proposed size classifications. MAIN OUTCOME MEASURES: Proportion of tumors classified in each category and melanoma-specific survival by category and stage. RESULTS: Of the 289 melanomas, 5% were classified as pT1, 63% as pT2, 22% as pT3, and 7% as pT4 according to TNM6. The corresponding percentages based on TNM5 were 8%, 17%, 63%, and 10%. Of pT2 tumors in TNM6, 4% came from pT1, 65% from pT3, and 4% from pT4 category of TNM5. Of 28 melanomas with extraocular growth, 29% were classified as pT2 in TNM6 rather than pT4 in TNM5. The 10-year survival estimate was 2 percentage points lower for pT1, 7 percentage points higher for pT2, 17 percentage points lower for pT3, and 13 percentage points lower for pT4 by TNM6 compared with TNM5; TNM6 (P<0.0001) and the modified alternative size classifications (P = 0.0022 and P = 0.0026) divided tumors according to prognosis better than TNM5. The 10-year survival for stage I, II, and III tumors was 2 percentage points lower, 7 points higher, and 23 points lower by TNM6, which was not better than TNM5 in separating patients according to prognosis (P = 0.47). The alternative size classifications provided more equal categories and fitted the data set better than TNM5 regarding prognosis. CONCLUSIONS: TNM6 is an improvement over TNM5 in some, but not all, respects. Areas for development include taking into account ciliary body involvement and extraocular extension in more detail and combining into each stage tumor categories with similar rather than different prognosis. An evidence-based, multicenter approach would be beneficial.

Cause of Death↗
PubMed1975

Sulfate and galactose metabolism in differentiating ciliary body and iris epithelia: autoradiographic and ultrastructural studies.

Immature and adult rat eyes were bisected and incubated with 35-SO4 and 3-U-galactose in short-term pulse-chase experiments. Autoradiographs (ARG) of the tissue revealed that very little sulfate is incorporated by the peripheral neural retina, the pigment epithelia of the retina, ciliary body, or iris. The inner, inverted optic cup cells at the ora serrata, i.e., those that are undergoing differentiation into the unpigmented epithelium of the ciliary body, incorporate large amounts of 35-sulfate into "fixable" macromolecules. The sulfate label is chased from the apically located Golgi apparatus to the basal surface of these cells within one hour. Ultrastructurally, these cells are beginning to develop lateral and basal invaginations of the plasma membrane characteristic of the adult secretory epithelial cells. Electron microscopic ARG show label associated with the plasma membranes. The sulfated macro-molecules at this site appear to be glycolipids and glycoproteins rather than glycosaminoglycans. The preferential synthesis of these macromolecules and their placement at the cellular site of aqueous humor production suggests a role for these sulfated substances in establishing, and perhaps maintaining, that secretory process. 3-H-galactose was incorporated into "fixable" macromolecules to some degree by all the neuroepithelial cells. After chase incubation, ARG showed a high concentration of label in differentiated retinal pigment epithelium (RPE), but not in undiffenentiated peripheral RPE. Ciliary body unpigmented and pigment epithelium, and iris muscle cells incorporate galactose, but to a lesser degree than either RPE or corneal endothelial cells.

Age Factors↗
PubMed1991

[Pars plana capsule resection for therapy of ocular hypotension syndrome caused by capsule shrinkage with ciliary body detachment].

A rare complication of extracapsular cataract extraction is hypotony due to capsular shrinkage, with consequent ciliary body detachment. A classic hypotony syndrome with progressive loss of visual acuity was observed in two patients, one with extracapsular aphakia and one with extracapsular pseudophakia. Each presented with a fibrotic, shrunken capsular bag and a secondary cataract. As the contraction forces appeared to derive predominantly from the periphery of a circumferentially fibrotic capsular bag, the lens capsule was operatively removed. A pars plana approach was used to access the equatorial capsular ring and visualize the ciliary body processes. The intraocular lens appeared to be stable and remained in situ. Postoperative elevation of intraocular pressure occurred, with improvement of hypotony symptoms, especially in the fundus. Visual acuity also improved, but was limited due to secondary cystoid edema.

Adult↗
PubMed1996

The effects of intravitreally injected endothelin-1 on the iris-ciliary body microvasculature in rabbits.

PURPOSE: We previously reported that intravitreal injection of 0.5 microg of endothelin-1 (ET-1) caused both a sustained reduction of intraocular pressure (IOP) and decreased aqueous production in the rabbit eye. On the theory that these effects might have resulted from a sustained reduction of blood flow to the ciliary body due to ET-1-mediated vasoconstriction, in the present study we attempted to determine if ET-1 causes any changes in the vascular caliber of the iris-ciliary body. METHODS: ET-1 solution (0.5 microg) was injected into the vitreous of one eye of each of 10 albino rabbits; the same amount of vehicle was injected into the contralateral eyes. One h following these injections in five of the rabbits and 24 h following them in the other five rabbits, ocular microvascular castings were obtained under controlled physiologic conditions, and the amount of vasoconstriction of the arterioles branching from the major arterial circle of the iris (MAC) and supplying the iris-ciliary body was measured by a scanning electron microscope and expressed as a percentage. RESULTS: The ET-1 caused a statistically significant focal vasoconstriction in the treated eyes as compared with the contralateral, control eyes (9.9% at 1 h and 6.2% at 24 h; both P = . 0001). CONCLUSIONS: Intravitreally injected ET-1 caused statistically significant, but only mild vasoconstriction of the arterioles supplying the ciliary processes.

Animals↗
PubMed1990

[Histopathological findings following cryo-coagulation of the ciliary body with a nitrogen-cooled probe].

A new cryoprobe was investigated in rabbits for experimental coagulation of the ciliary body. In a one-step procedure, the cyclodestructive effect was achieved by cooling the cryoprobe down to -100 degrees C without significant lens damage. The histological investigation showed extensive necrosis of the ciliary epithelium 2 h and 2 days after the freezing damage. After 2 weeks and 2 months, fibrous atrophy of the entire segment of the ciliary body could be observed.

Animals↗
PubMed1977

Microsomal preparations of normal bovine iris-ciliary body generate prostacyclin-like but not thromboxane-A2-activity.

Indomethacin-treated bovine iris-ciliary body microsomes (IBIM) have been studied for their ability to convert PG endoperoxides into either thromboxane-A2 (TxA2)-like or prostacyclin (PGI2)-like activity. The biological activity of the ocular tissue microsomes were compared with either indomethacin-treated human platelet microsomes (for TxA2-like activity) or rabbit aorta microsomes (for PGI2-like activity) under appropriate incubation conditions. No evidence could be found for the formation of TxA2-like activity from PG endoperoxides by the IBIM. In contrast, when the IBIM were incubated with PGH2 for 1 min at 22 degrees C without cofactors, PGI2-like activity was produced, causing profound relaxation of the isolated dog coronary artery preparation without contracting the rabbit aorta and inhibiting arachidonic acid-induced platelet aggregation. Equivalent quantities of boiled IBIM failed to alter the biological activity of PGH2 under identical conditions. Tranylcypromine (500 microgram/ml) completely abolished the appearance of PGI2-like activity. Furthermore, the PGI2-like activity found was stable for 10 min at 22 degrees C at pH 8.5 but completely lost under similar conditions at pH 5.5. It is concluded that microsomal preparations of normal bovine iris-ciliary body can synthesize PGI2-like activity in substantial amounts but not TxA2-like activity.

Animals↗
PubMed2004

Have choroidal and ciliary body melanomas changed during the period 1955-2000?

PURPOSE: To establish whether the presentation of choroidal and ciliary body melanomas and patient survival have changed during the period 1955-2000. METHOD: The study included 209 unselected patients (97 men, 112 women) from Arhus County during the period 1955-2000. The median age at treatment was 64 years (range 26-88 years). The disease course from first symptom through clinical and histopathological findings to death was described in a historical follow-up design. Time trends were evaluated. RESULTS: Treatment modality changed over time from enucleation to an almost equal distribution between enucleation and radiation brachytherapy. The age at treatment, or, alternatively, at diagnosis, increased significantly (p = 0.04). No significant time trend was seen for largest basal tumour diameter (p = 0.08) or tumour height (p = 0.27). The clinical and histopathological findings did not show any consistent time trends. No significant time trend was found for melanoma-specific survival (p = 0.96) or overall survival (p = 0.33). CONCLUSION: No consistent time trends were seen in clinical and histopathological tumour presentation and survival in patients with choroidal or ciliary body melanomas. The increase in age at treatment was in line with an increase in life expectancy in Denmark.

Adult↗
PubMed1990

Fluorescein angiography in ciliary body melanomas.

We retrospectively studied the value of iris fluorescein angiography in predicitng benignity or malignancy in 10 cases of ciliary body melanoma with iris extension. No correlation between fluorescein-angiographic appearance and histopathologic features was observed. Fluorescein angiography adds little to the management of ciliary body melanomas with iris extension.

Adult↗
PubMed1979

[Contribution to the epithelial tumors of the ciliary body (clinical, histopathological and electronmicroscopical observation) (author's transl)].

An adenoma of the non pigmented epithelium of the ciliary body was supposed to be an irisciliary body melanoma (32P-test positive) and was treated by irido-cyclectomy. Vision acuity remained 0,4 one year after operation. The tumor formed adenoid tubes lined with a cubical or cylindrical epithelium. The cytoplasm of all tumorcells was threaded with compactly arranged tonofilaments. The histopathological examination showed unequivocal the benignant character of this tumor. Nevertheless the tumorcells were infiltrating the deep scleral layer in one place. Also the lens was deformed by the tumor and developed a local opacity in the periphery. It is refered to the difficulty of a clear histopathological distinction between adenomas, adenocarcinomas and pseudo-adenomatous hyperplasia of the ciliary body (Fuchs adenoma).

Adenocarcinoma↗
PubMedDate not supplied

Ciliary body ablation: where are we and how did we get here?

Management of intraocular pressure remains the cornerstone of glaucoma treatment. Related medical and surgical practices involve increasing aqueous outflow or decreasing aqueous production. Filtration procedures that increase aqueous outflow are the first-line surgical defense in glaucoma. However, some cases of glaucoma are resistant to such treatment. In these cases, ciliary body ablation by various methods has had substantial success. Surgical manipulation of aqueous production has been used in glaucoma management since the turn of the century. Techniques have progressed markedly as technology has produced more discrete therapies designed to decrease aqueous production by destroying ciliary body epithelium. Over the past 90 years success has been achieved with a wide range of techniques, from surgical disinsertion of the ciliary body to recent laser and ultrasound techniques. With the development of more precise contact lasers and endoscopic visualization, side effects have been reduced and clinical success rates increased.

Aqueous Humor↗
PubMed1993

[Results of cyclo-cryocoagulation of the ciliary body with probe temperatures of -70 degrees C and -82 degrees C in glaucoma].

Cryocoagulation of the ciliary body has few applications. Cryotherapy in our study was standardized: 8 applications, 4 mm posterior to the limbus, 55 s, 2.5-mm-diameter cryoprobe. The aim of this research was to optimize the method by comparing the side effects of the treatment and the results of 128 operations as seen at follow-up examinations. When an applicator at -70 degrees C had been used, 54% of 52 eyes showed an IOP < 21 mmHg 12 months after operation. In all cases and adjuvant therapy was necessary. The IOP in 73% of these eyes rose to 30 mmHg for short periods. It was necessary to reoperate in 39% of the whole group. When a cryoprobe at -82 degrees C had been used IOP was found to have normalized in 89% of 76 eyes. In this group 34% of cases needed no other therapy. The IOP in the treated eyes showed peaks up to 30 mmHg in 34%. We performed revision operations in 7.9%. It was only possible to normalize the IOP of hemorrhagic glaucoma and glaucoma connected with PEX by using -82 degrees C applicator. Examinations over 30 months after treatment show nearly the same results. Side effects of cryocoagulation of ciliary body were observed. Postoperative IOP peaks exceeding 55 mmHg were recorded in 10% of cases. These can be avoided by osmotic therapy. The anterior chamber was inflamed with exudation of fibrin in about 4% of patients treated with a -70 degrees C probe and 16% treated with one at -82 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1998

Distribution of prognostically important vascular patterns across multiple levels in ciliary body and choroidal melanomas.

PURPOSE: To investigate the validity of assigning patients whose eyes have been removed for ciliary body or choroidal melanoma to risk groups for metastasis based on the identification of microcirculatory patterns in one cross-section taken from the center of the tumor. METHODS: Multiple levels were cut through the blocks of 15 ciliary body or choroidal melanomas until the tumor was exhausted. Each level was examined for the presence of microvascular networks and parallel vessels with cross-linking histologic features strongly associated with death from metastatic melanoma. RESULTS: The central histologic section did not contain either microvascular networks or parallel vessels with cross-linking in eight tumors, nor were these patterns encountered in any of the more peripheral levels of the tumor. Seven tumors contained at least one focus of either microvascular networks or parallel vessels with cross-linking in the central histologic section. In two tumors, at least one of these patterns appeared in all histologic levels; in five tumors, at least one of these patterns appeared through multiple levels until just before the tumor was exhausted from the block (0.24 to 0.85 mm from the edge of the tumor). CONCLUSIONS: This study suggests that the prognostic classification of uveal melanoma based on the histologic profile of the microcirculation may be consistent throughout the tumor depth.

Choroid Neoplasms↗
PubMed2003

In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors.

Strategies for retargeting adenoviral (Ad) vectors have been developed, but their in vivo efficacy remains to be demonstrated. Gene delivery to specific ocular cell types represents an approach to treating many diseases that cause irreversible blindness. One of these cell types, the photoreceptor (PR), is not infected by standard Ad5-based vectors. We evaluated gene delivery after intraocular injection of Ads pseudotyped with three different fiber proteins and found three distinct patterns of infection. An intravitreally injected Ad5 vector readily infected the iris, corneal endothelium, and ciliary body, while few cells in the retina expressed transgene product. In contrast, an Ad3-pseudotyped virus selectively transduced ciliary body, of interest for treating diseases such as glaucoma. A vector pseudotyped with the fiber protein of Ad37 transduced PRs as well as ciliary body. This finding has potential application to the treatment of retinal degenerative or neovascular diseases. These studies demonstrate cell type-selective gene delivery in vivo with retargeted Ads, provide information about the cellular tropisms of several Ad serotypes, and should lead to improved strategies for preserving vision.

Adenoviridae↗
PubMed1997

Synergistic rise in Ca2+ produced by somatostatin and acetylcholine in ciliary body epithelial cells.

The purpose of these experiments was to demonstrate the presence of somatostatin receptors on the nonpigmented epithelial cells of the rabbit ciliary body and their link with intracellular Ca2+ homeostasis. Freshly excised rabbit ciliary processes and nonpigmented cell layer, explants were loaded with the fluorescent dye fura-2, and free-Ca2+ concentration ([Ca2+]i) in the nonpigmented cells was measured with fluorescence ratio imaging. The cells were continuously perfused, and drugs were added to the perfusate. Somatostatin-14 (SS14, 0.1-1.0 microM) or acetylcholine (ACh, 10 microM) applied alone produced small increases in [Ca2+]i. However, SS14 (0.1 microM) in combination with ACh (10 microM) induced a massive increase in [Ca2+]i (25.7 +/- 3.3 times the baseline level, n = 28). The dose-response curve for SS14 (in the presence of 10 microM ACh) was sigmoidal with an EC50 of 3.9 nM and Hill coefficient of 2.5, indicating the requirement for multiple SS receptor activation. Somatostatin-28 could mimic the effect of SS14, although a much higher concentration was required. Shifting the SS14 dose-response curve to the right by about two-orders of magnitude resulted in a fit to the SS28 data. The response to ACh + SS14 could not be blocked by the alpha 2-adrenergic blocker yohimbine (Yoh, 10 microM) or the A1-specific adenosinergic antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM). Incubation of the tissue with pertussis toxin (PTx, 1 microgram ml-1) did not alter the response to ACh alone but eliminated the synergistic effect of somatostatin. We conclude that nonpigmented epithelial cells of the rabbit ciliary body possess a novel somatostatin receptor whose activation can synergistically potentiate the rise in [Ca2+]i produced by ACh. This potentiation appears to occur via a pertussis-toxin-sensitive pathway, perhaps through Gi.

Acetylcholine↗