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PubMed1984

Electrical potential, resistance, and fluid secretion across isolated ciliary body.

Rabbit ciliary epithelium was mounted with the sclera and lens still attached. The potential measured in physiological bathing medium was 1.29 +/- 0.18 mV initially, but dropped to 0.66 +/- 0.34 mV, then became stable for 2 hr or more. The resistance of the epithelium was measured by comparing total trans-tissue resistance before and after treatment with Triton X-100, ethanol, or distilled water. The calculated resistance with correction for epithelial surface area was found to be 1504 +/- 452 omega, in six experiments. Fluid secretion was measureable against a hydrostatic gradient when identical solutions bathed both sides of the preparation. Ouabain caused opposite responses when applied to either side of the preparation, indicating that it does not readily cross the epithelial barrier. The evidence presented suggests that the ciliary epithelium is a 'tight' rather than a 'leaky' epithelium, and that fluid secretion in the normal ciliary epithelium occurs by active transport rather than by ultrafiltration.

Animals↗
PubMed1994

Characterization of a novel family of ciliary body glycoproteins.

PURPOSE: To isolate and characterize ciliary body epithelial antigens reactive with a monoclonal antibody, 2B4.14.1. METHODS: A mouse monoclonal antibody generated against human corneal endothelium, 2B4.14.1 reacts with nonpigmented epithelium of human and guinea pig ciliary bodies. The ciliary body proteins reactive with 2B4.14.1 were identified by Western blotting and were partially purified by affinity chromatography with 2B4.14.1 coupled to a solid support matrix. Carbohydrate components of the antigenic molecules were analyzed by lectin chromatography and by digestion with the enzymes N-glycosidase F and endoglycosidase F. The cellular and subcellular distribution of the antigens was examined by immunoperoxidase staining and by immunoelectron microscopy of ultracryotome sections of ciliary body. RESULTS: 2B4.14.1 reacted with families of guinea pig and human ciliary body glycoproteins with estimated molecular weights ranging from 250 to 325 kD. In Western blots of samples reduced before electrophoresis, the high molecular weight bands were replaced by weakly reactive bands at 115 to 130 and 210 kD, indicating that the 2B4.14.1 ligands have disulfide bonds. 2B4.14.1 ligands from both guinea pig and human ciliary body were bound by immobilized lectins, including concanavalin A, Datura stramonium lectin, and Lens culinaris hemagglutinin, which recognize components of N-linked oligosaccharides. Guinea pig ciliary body antigens digested with N-glycosidase F and endoglycosidase F failed to react with 2B4.14.1 in Western blots, confirming the presence of N-linked oligosaccharide chains and indicating that they form an integral part of the 2B4.14.1-reactive antigenic site. Molecular weight shifts of glycosidase-digested antigens were consistent with the presence of two to four N-linked oligosaccharide units. In immunoperoxidase-stained sections of guinea pig and human ciliary body, 2B4.14.1 reacted primarily with nonpigmented epithelial cells. Staining of guinea pig epithelial cells was fairly uniform; staining of human epithelial cells was concentrated on the basal surface. By immunoelectron microscopy, a majority of the 2B4.14.1 antigenic reactivity was localized immediately external to the nonpigmented epithelial cell plasma membrane. CONCLUSIONS: 2B4.14.1 reacts with a novel family of high molecular weight glycoproteins associated with the nonpigmented epithelial cell surface in guinea pig and human ciliary body.

Aged↗
PubMed1995

Mixed cell malignant melanoma of the ciliary body.

Malignant melanomas of the ciliary body are uncommon tumors and the ratio of occurrence in the ciliary body to that in the choroid is 1:10. These tumors may have a nodular or diffuse growth pattern or combination of the two. The authors recently encountered a malignant melanoma of the ciliary body. After evaluation of the results of clinical examination, computed tomography(CT) and magnetic resonance imaging(MRI) a tentative diagnosis of malignant melanoma of the ciliary body in the left eye was made and an enucleation was done. Histopathological examination revealed the case as a mixed cell malignant melanoma of the ciliary body. The patient was followed up for approximately one year with no signs of metastasis or recurrence.

Aged↗
PubMed1996

Comparison of nucleoside transport binding sites in rabbit iris-ciliary body and cultured rabbit nonpigmented ciliary epithelial cells.

The iris-ciliary body (ICB) is a site of action for topically applied antiglaucoma drugs. Moreover, adenosine has been implicated as a modulator of aqueous humor dynamics. The present study compares the binding of the nucleoside transporter probe, [3H]nitrobenzylthioinosine ([3H]NBMPR), to homogenates prepared from rabbit ICB and a cultured rabbit nonpigmented ciliary epithelial cell line (NPE) to determine whether NPE can be used as an experimental model to study the nucleoside transporter. Linear transformation of the saturation binding data revealed that [3H]NBMPR binds to a homogeneous population of binding sites with similar binding affinities (Kd = 0.3 +/- 0.1 and 0.6 +/- 0.1 nM in NPE and ICB, respectively). However, the maximal binding capacity in NPE (Bmax = 288 +/- 54 fmol/mg protein) was significantly higher than that in ICB (Bmax = 154 +/- 17 fmol/mg protein). Selected inhibitors of the nucleoside transport system and structural analogs of adenosine inhibited the binding in both homogenate preparations with a similar rank order of potency: NBMPR > DPY > CV-1808 > CHA > R-PIA > S-PIA > 2-CADO > NECA. The results suggest that NPE is a useful model which could be used for characterizing the nucleoside transporter in ICB and for the screening of nucleoside transport inhibitors as potential antiglaucoma drugs.

Adenosine↗
PubMed2004

Looking at an oft-overlooked part of the eye: a new perspective on ciliary body development in chick.

The ciliary body is an essential tissue for the development and homeostasis of the vertebrate eye. Embryonically, the epithelial portion of the ciliary body derives from the neuroepithelium of the optic cup, however, it differentiates into a secretory tissue and produces an aqueous humor that sustains the lens and cornea, and maintains the requisite pressure within the orb. The unique differentiation of this portion of the optic cup is little understood. This article reviews what is known about the development of the ciliary body and presents some preliminary findings that may lead to a new model for the formation of the ciliary body.

Animals↗
PubMed1981

Proton-beam irradiated epithelioid cell melanoma of the ciliary body.

A malignant ciliary body melanoma received proton-beam irradiation. After an apparent failure of the tumor to respond, the eye was enucleated. A predominantly epithelioid cell tumor appeared viable by light microscopy, and a low degree of mitotic activity persisted, despite therapy. The tumor cells, however, displayed degenerative changes ultrastructurally, presumably results of the radiotherapy. These consisted of numerous cytoskeletal filaments, lipid vacuoles, prominent phagolysosomes, and nuclear convolutions and fragmentations. The mitochondria were fewer in number in the present tumor than typically encountered in epithelioid cells. A rare leptomeric structure was discovered, probably an organizational modification of the cytoplasmic filaments. The tumor's capillaries showed radiation-induced changes in terms of thickened basement membranes and perivascular fibrin deposition. The foregoing features are indicative of cellular and metabolic injury from the radiotherapy, but these were evidently not sufficiently injurious to sterilize the tumor.

Adult↗
PubMed2006

Accommodative ciliary body and lens function in rhesus monkeys, I: normal lens, zonule and ciliary process configuration in the iridectomized eye.

PURPOSE: The underlying causes of presbyopia, and the functional relationship between the ciliary muscle and lens during aging are unclear. In the current study, these relationships were studied in rhesus monkeys, whose accommodative apparatus and age-related loss of accommodation are similar to those in humans. METHODS: Centripetal ciliary body and lens equator movements were measured during accommodation in 28 eyes of 21 rhesus monkeys (ages, 5.7-26 years) by goniovideography. Ultrasound biomicroscopy was performed in 21 eyes of 17 monkeys. Narrowing of the angle between the anterior aspect of the ciliary body and the inner aspect of the cornea was used as a surrogate indicator of forward ciliary body movement during accommodation. RESULTS: Average centripetal ciliary body movement in older eyes (age > or =17 years, n = 16) was approximately 20% (0.09 mm) less than in young eyes (age, 6-10 years, n = 6), but not enough to explain the 60% (0.21 mm) loss in centripetal lens movement nor the 76% (10.2 D) loss in accommodative amplitude. Average forward ciliary body movement was 67% (49 degrees ) less in older (n = 11) versus young (n = 6) eyes. Maximum accommodative amplitude correlated significantly with the amplitude of centripetal lens movement (0.02 +/- 0.003 mm/D; n = 28; P < 0.001) and with forward ciliary body movement (3.34 +/- 0.54 deg/D; n = 21; P = 0.01). CONCLUSIONS: Decreased lens movement with age could be in part secondary to extralenticular age-related changes, such as loss of ciliary body forward movement. Ciliary body centripetal movement may not be the limiting component in accommodation in the older eye.

Accommodation, Ocular↗
PubMed2006

Molecular events in early development of the ciliary body: a question of folding.

Ciliary body morphogenesis is a complicated, multi-step process requiring coordinated changes in cell shape, flexure of epithelial sheets and dynamic shifts in mitotic rates. Very little is known of how these cellular events are triggered or regulated. This review summarises current models of ciliary body morphogenesis. The role of intraocular pressure as a driver of morphogenesis is re-evaluated in the light of new information. An update on the role of the lens in ciliary body morphogenesis is presented. In the second part of the review current gene expression data is related to ciliary body morphogenesis. In particular the role of Bmp4 and its downstream target genes are discussed, with novel gene expression patterns of Bmp4 and Tgfbeta1i4 being presented.

Animals↗
PubMed2001

[Malignant melanoma of the ciliary body. A diagnostic problem].

BACKGROUND: Ciliary body melanoma is often diagnosed too late and therefore has a poor prognosis. The circular infiltration of the iridocorneal angle by malignant cells can lead to secondary glaucoma, often misdiagnosed as pigmentary glaucoma. MATERIAL AND METHODS: In a 40-year-old patient the diagnosis "atypical pigmentary glaucoma" was made due to elevated intraocular pressure and pigmentation of the iridocorneal angle; no changes were present in the iris. In a second case pronounced pigmentation of the chamber angle and secondary glaucoma led to the clinical diagnosis of a ring melanoma and resulted in enucleation of the globe. RESULTS: In the first case, increasing pigmentation of the chamber angle over 4 weeks led to the presumed diagnosis of a ring melanoma. Histopathological evaluation confirmed the diagnosis of a ring melanoma of the ciliary body. In the second case histology revealed retinal detachment with intraocular bleeding without intraocular melanoma. The pigmentation in the lower part of the chamber angle was due to hemosiderosis. CONCLUSION: Diagnosis of ciliary body melanomas may be difficult in some cases due to its similarity to other eye diseases. The differential diagnosis of malignant melanoma of the ciliary body should be considered in cases of unilateral pigmentary glaucoma.

Adult↗
PubMed1997

Moxonidine-induced inhibition of norepinephrine release in monkey and rabbit ciliary bodies: role of cGMP.

This study was designed to determine whether in isolated rabbits iris-ciliary bodies and monkey ciliary bodies, cGMP plays a role in the action of moxonidine, an alpha 2- and imidazoline (I1) receptor agonist. In field-stimulated rabbit iris-ciliary bodies, dose-related inhibition of norepinephrine release was induced by 8-Br-cGMP, moxonidine or sodium nitroprusside; 8-Br-cGMP in combination with moxonidine did not enhance inhibition of norepinephrine release. Sodium nitroprusside at intermediate and high concentrations stimulated cGMP production in rabbit iris-ciliary bodies, whereas moxonidine stimulated cGMP production modestly only at a high concentration. When iris-ciliary bodies were pretreated with a low concentration of moxonidine, sodium nitroprusside-stimulated cGMP production was enhanced from 1.6 to 2.2 pmol/mg protein. In field-stimulated monkey ciliary bodies, both sodium nitroprusside and moxonidine inhibited norepinephrine release. Pretreatment of electrically stimulated monkey ciliary bodies with sodium nitroprusside enhanced the suppressive effect of moxonidine on norepinephrine release. In monkey ciliary bodies, moxonidine raised cGMP production more than sodium nitroprusside did, but there was no synergism in cGMP production by combined treatment with moxonidine and sodium nitroprusside. These results suggest that cGMP could play a role in the ocular action(s) of moxonidine in ciliary bodies; however, involvement of cGMP in the action of moxonidine in monkey ciliary bodies seems to be more pronounced than in rabbit iris-ciliary bodies.

Animals↗
PubMed1981

Transport and metabolism of pyridoxine in rabbit iris--ciliary body.

Isolated rabbit iris--ciliary body preparations were found to accumulate 3H-pyridoxine by a mechanism that was time- and temperature-dependent, saturable in part, but not altered by omission of oxygen or specific ions. Tissue accumulation was only partially energy-dependent, and metabolic inhibitors had only small effects. Other B6 vitamers markedly blocked accumulation. Metabolism of 3H-pyridoxine within the tissue was extensive. After 60 min incubation with 3H-pyridoxine, about 65% of the radioactivity in the iris--ciliary body was associated with phosphorylated vitamers which did not efflux from the tissue as readily as did the nonphosphorylated forms. Unaltered pyridoxine accounted for only 16% of intracellular 3H-B6, and this did not represent accumulation against a concentration gradient. A similar saturable uptake process occurred in vivo. These data were consistent with the hypothesis that pyridoxine was accumulated by facilitated diffusion with intracellular trapping of phosphorylated metabolites.

Animals↗
PubMed1987

Distribution and properties of beta-adrenergic receptors in human iris-ciliary body.

beta-Adrenergic receptors from the iris-ciliary body of human eyes removed shortly after death were studied using membranes prepared by isopycnic centrifugation of tissue homogenates. This procedure separates uveal melanin pigment from plasma membranes and reduces nonspecific binding of 125I-iodopindolol. The observed binding of 125I-iodopindolol was of high affinity (Kd = 78 +/- 6.6 pM), saturable, and fully reversible (t1/2 = 4.6 min). Scatchard plots were linear and revealed a Bmax of 134 +/- 20 fmol/mg of protein from the whole iris-ciliary body. The affinities of the receptors for a series of agonists and antagonists were determined. The order of potency for the inhibition of the binding of the radioligand by antagonists was ICI 118,551 greater than MK950 greater than propranolol greater than ICI 89,406 greater than metoprolol. This order of potency is characteristic of beta-adrenergic receptors of the beta 2 subtype. Preparations of iris-ciliary body were also subjected to microdissection prior to density gradient centrifugation to permit the study of beta-adrenergic receptors in the ciliary processes, ciliary body, and iris. Each of these regions was found to contain approximately one third of the total number of beta-adrenergic receptors in the human iris-ciliary body. The highest density of receptors was located in the ciliary processes (180 +/- 40 fmol/mg of protein), while the density of receptors in the iris (98 +/- 7.5 fmol/mg of protein) and ciliary body (less the processes) (42 +/- 17 fmol/mg of protein) was notably lower. Only beta 2-adrenergic receptors are detectable by competition experiments in the iris-ciliary body as a whole, or in the individual preparations of iris, ciliary processes, or ciliary body; however, microdissection and analysis of beta-adrenergic receptor subtypes in isolated ciliary muscle permitted detection of a small number of beta 1-adrenergic receptors. beta 1-Adrenergic receptors comprised about 10% of the total number of beta-adrenergic receptors in the whole iris-ciliary body. The finding that most of the beta-adrenergic receptors in the human iris-ciliary body are of the beta 2 subtype may be of significant therapeutic importance in the medical management of glaucoma.

Adolescent↗
PubMed1985

Detoxification of hydrogen peroxide by the rabbit iris-ciliary body.

When the intact rabbit iris-ciliary body was incubated in Tyrode's solution containing 10(-4) M hydrogen peroxide, the concentration of hydrogen peroxide remaining in solution diminished rapidly. The iris-ciliary body was homogenized and centrifuged at 100 000 g. It was observed that the hydrogen peroxide detoxification activity was resident primarily in the 100 000 g supernatant and not in the pellet. The hydrogen peroxide detoxification activity was found to be inactivated by heat and to be non-dialyzable. Gel filtration chromatography experiments revealed that breakdown of hydrogen peroxide by the ciliary body was not a 'bulk effect' due to generalized oxidation of tissue constituents. In fact, the active principle, localized by gel filtration chromatography, identified closely with catalase. These observations indicate that catalase within the iris-ciliary body enables the tissue to detoxify hydrogen peroxide from solution. Catalase might protect the iris-ciliary body from damage by hydrogen peroxide generated by normal physiological or pathophysiological conditions.

Animals↗
PubMed1995

[Continuous ultrasound biomicroscopic imaging of accommodative changes in the human ciliary body].

BACKGROUND: Slitlamp observations of the position of the ciliary body behind the iris root are possible only in cases of gross anatomic, and probably also functional, abnormalities. This study was performed to investigate physiological changes of the human ciliary body configuration during accommodation. MATERIAL AND METHODS: We used the 50 MHz ultrasound biomicroscope to measure the ciliary body changes in 5 left eyes of normal subjects during accommodation, while the right eye, wearing corrective spectacles, focussed Snellen letters at a distance of 3 m. For desaccommodation plus lenses were utilized, while negative lenses were applied to blur vision as a stimulus for accommodation. During postprocessing the best images of the video sequence were recalled on a monitor and the profile of the ciliary body was manually drawn on a transparent folder. For interpretation we used a projection system with vector analysis. RESULTS: During accommodation there is a shift of the ciliary body anteriorly toward the scleral spur and in the direction of the lens equator. In 4 out of 5 eyes a contact between the ciliary body and the posterior iris surface could be demonstrated. There was a measurably widening of the anterior chamber angle in 3 out of 5 eyes. CONCLUSIONS: Ultrasoundbiomicroscopy seems to be a way for assessing ciliary body deformation during accommodation. Our results are in accordance with histologic and gonioscopic findings and confirm biomechanical theories of the accommodation process. Further investigations including online digital image processing will be necessary to evaluate accommodation in its complexity.

Accommodation, Ocular↗
PubMed1998

Expression of a copper-containing amine oxidase by human ciliary body.

PURPOSE: To examine the molecular structure and ultrastructural distribution of a novel amine oxidase in human ciliary body. METHODS: Human ciliary bodies were solubilized with a nonionic detergent. The solubilized material was subjected to affinity chromatography with 2B4.14.1, a monoclonal antibody which recognizes a family of ciliary body glycoproteins. Proteins eluted from the affinity column were further separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Peptides produced from a 2B4.14. 1-reactive protein with an approximate molecular weight of 100 kDa were analyzed by Edman degradation. The protein thus identified was further examined by Western blotting and immunoelectron microscopy with anti-peptide antisera. RESULTS: Peptide sequences from the 100 kDa ciliary body protein were identical to the predicted protein sequence of an amine oxidase identified recently in a human placental cDNA library. The identity of the ciliary body protein was confirmed by Western blotting with rabbit antiserum generated against the predicted carboxy-terminal peptide of human placenta amine oxidase. Western blotting under nonreducing conditions and following glycosidase digestion indicated that the native enzyme is a disulfide-linked homodimer with multiple N-linked oligosaccharide side chains. By immunoelectron microscopy, the ciliary body amine oxidase was localized to the plasma membranes of inner epithelial cells. CONCLUSIONS: Human placenta amine oxidase is present on the plasma membranes of ciliary body inner epithelial cells. This finding provides a potential explanation for amine oxidase enzyme activity detected in previous studies of anterior segment tissues. Though the functional role of human placenta amine oxidase in the eye is unclear, it may contribute to the production of H2O2 in aqueous humor.

Aged↗
PubMed1995

Relation between the microcirculation architecture and the aggressive behavior of ciliary body melanomas.

PURPOSE: To study the relation between vascular patterns and the biologically aggressive behavior of ciliary body melanomas. METHODS: The authors compared the frequency distribution of vascular patterns by location for 234 uveal melanomas (54 tumors involving the ciliary body, and 180 without ciliary body involvement). Stepwise Cox regressions (for the endpoint of time-to-death due to melanoma), performed separately for melanomas with and without ciliary body involvement, included the following variables: size, vascular patterns, cell type, mean of the largest nucleoli, mitoses, tumor infiltrating lymphocytes, age, and sex. A separate Cox regression procedure included the variable of tumor location. Kaplan-Meier survival curves were generated for time to melanoma death with ciliary body involvement and melanomas without ciliary body involvement for tumors containing or lacking vascular networks. RESULTS: These vascular patterns appear more often in the ciliary body than in the choroid: parallel vessels (P = 0.022), arcs (P = 0.003), and parallel with cross-linking, arcs with branching, and loops and networks (all P = 0.0001). Stepwise regression for tumors confined to the choroid indicated that the presence of networks was the most significant variable (P = 0.0001); stepwise regression for tumors with ciliary body involvement suggested that only one variable, networks, was significant (P = 0.0066). Kaplan-Meier survival estimates indicated that the survival of patients with tumors containing networks in the ciliary body was comparable to those containing networks in the choroid. CONCLUSION: Regardless of location, ciliary body or choroid, the presence of vascular networks shortens survival. The tumor location does not enter a stepwise Cox regression model when vascular patterns are included as variables. Therefore, the aggressive behavior of ciliary body melanomas appears to be related to the tendency for vascular networks to develop in this location.

Adolescent↗