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PubMed1988

Characteristics of ascorbate transport in the rabbit iris-ciliary body.

The accumulation and efflux of [14C]ascorbic acid by the rabbit iris-ciliary body were examined in vitro. Accumulation of labelled ascorbate was observed to be reduced significantly by ouabain(10(-4) M), low sodium solutions, 0 degree C and dinitrophenol (10(-3) M). These findings suggest that the ascorbate uptake mechanism is linked to metabolism via the sodium gradient. In addition, labelled ascorbate uptake was diminished by both phloretin (10(-4) M) and phlorhizin-(10(-4) M), two glucose transport inhibitors. Clear differences were observed between the characteristics of [14C]ascorbic acid uptake and efflux. In contrast to the uptake, 14C-labelled, ascorbate efflux from the iris-ciliary body was not significantly altered by dinitrophenol, phloretin, or phlorhizin. The observation that the efflux of labelled ascorbate was not diminished by either dinitrophenol or ouabain supports the concept that the process of ascorbate efflux from the iris-ciliary body is passive and not sodium dependent. It was demonstrated that a vigorous rate of [14C]ascorbate efflux from the iris-ciliary body persisted even when the external ascorbate level was elevated to 1 mM, the concentration found in aqueous humor.

Animals↗

PubMed1996

Mapping the Location of Prognostically Significant Microcirculatory Patterns in Ciliary Body and Choroidal Melanomas.

The microcirculation of choroidal and ciliary body melanomas is remodeled into architecturally distinctive patterns. The presence of two histologic microvascular patterns, networks and parallel vessels with cross-linking, is strongly associated with metastasis. This study was designed to test the hypothesis that networks and parallel vessels with cross-linking patterns are not distributed evenly throughout the tumor. From a set of 234 eyes removed for ciliary body or choroidal melanoma, 152 tumors contained at least one focus of either vascular networks or parallel vessels with cross-linking. Histological cross-sections were digitized and foci of tumor containing these patterns were pseudocolorized so that their location within the periphery or central tumor zone could be mapped. Ciliary body and choroidal melanomas vary widely in size and shape and it is not appropriate to describe the periphery of a tumor as a fixed value because in a small tumor, the periphery thus defined would occupy a larger percent area than in a larger tumor. In this study, the peripheral and central zones of each tumor were described by a function that was constant from tumor to tumor, allowing the width of the peripheral and central zones to vary proportionally with tumor size. Observed counts of vascular patterns per zone were compared statistically with expected counts based upon the percent area occupied by the peripheral and central zones. Discrete foci of networks and parallel with cross-linking vessels are over-represented in the tumor periphery (p < 0.0001).

Journal Article↗

PubMed2006

Analysis of expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human ciliary body after latanoprost.

PURPOSE: To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body. METHODS: Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human ciliary body tissue and explant cultures of ciliary body smooth muscle (CBSM) cells. CBSM cell cultures were treated with vehicle control or latanoprost acid for 24 hours. Quantitative RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS: The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 as well as TIMP-1 to -4 were found in ciliary body tissue and CBSM cells. MMP-9 was present after latanoprost treatment. In control CBSM cells, the relative expression of MMP mRNA was MMP-2 and -14 > MMP-24 > MMP-1, -11, -15, -16, and -19 > MMP-3 and 17, > MMP-12. The relative expression of TIMP mRNA was TIMP-2 > TIMP-1 > TIMP-3 > TIMP-4. Latanoprost increased MMP-3 (in three of five cultures), MMP-17 (in four of five cultures), and TIMP-3 (in all five cultures); MMP-1, -2, -12, -14, -15, and -16 and TIMP-4 were downregulated. CONCLUSIONS: The transcription of the genes for MMP-3 and -17 is increased by latanoprost treatment. MMP-9 is present after latanoprost treatment and may also mediate ECM changes. TIMP-3 is upregulated and may compensate for the increase in MMPs. These coordinated changes could be expected to mediate the latanoprost-induced alteration of ECM in the ciliary body.

Adult↗

PubMed1979

[Leiomyoma of the ciliary body - misdiagnosis leading to an unconventional but successful surgical approach].

Report on a leiomyoma of the ciliary body in a 12-year-old girl. The clinical findings were misinterpreted as a traumatic ciliary body cyst because of the associated iridodialysis, the fact that the tumor could be transilluminated, because it appeared cystic on ultrasonography, and because there was a history of severe cranial trauma. In the course of an attempt to puncture the presumed cyst a cherry-sized ciliary body tumor was revealed. It proved possible to shell this out without performing an iridocyclectomy. An elective enucleation would have been performed had the true diagnosis been known preoperatively. Due to the misdiagnosis and the resulting unconventional approach the eye was preserved with some residual functions. the histological picture was that of a leiomyoma, a tumor rarely found in the ciliary body. The histological and electronmicroscopic appearance are described and compared with the few cases previously reported.

Adolescent↗

PubMed1995

[Morphometry of the ciliary body using ultrasound biomicroscopy].

High-frequency ultrasound biomicroscopy (UBM) is a new method which allows in vivo visualisation of anterior segment structures with high resolution but limited penetration. Using this modality we wanted to examine the ciliary body and measure its total length and depth and look for correlations with the axial eye length. A special technique with external markers was developed to measure the total length of the ciliary body using two UBM pictures. In 83 patients the mean ciliary body length was 5.2 mm nasally and 5.7 mm temporally. The depth of the ciliary body was 1.2 mm nasally and 1.4 mm temporally. A correlation could be demonstrated between the axial eye length and the ciliary body measurements. As our measurements are reproducible and consistent with recent histological studies, high-resolution UBM can be regarded as a reliable method for in vivo visualisation and quantitative analysis of the ciliary body.

Adult↗

PubMed2003

Incubation of porcine iris-ciliary bodies to study the mechanisms by which nitric oxide donors lower intraocular pressure.

BACKGROUND: We previously reported that several nitric oxide (NO) donors, guanylate cyclase activators, and cyclic GMP lower intraocular pressure (IOP) in rabbits. MATERIAL/METHODS: This study evaluated a novel method for studying cGMP production in the iris-ciliary body after the administration of different NO donors and guanylate cyclase activators. Tissue samples of porcine iris-ciliary body were incubated for 30 or 60 minutes with the test compounds and with or without the phosphodiesterase inhibitor zaprinast. The concentration of cGMP in the iris-ciliary body as an indicator of soluble guanylate cyclase activation was measured by radioimmunoassay. RESULTS: The tested NO donors - SNOG, NONOate, NOR-3, and SNAP - were shown to release NO in incubation medium, and clearly increase cGMP concentration in the iris-ciliary body. Cyclic GMP production was 2-5 times higher with nitrosocaptopril and about 10 times higher with SNP than in the unstimulated control tissue incubation. Captopril, the reference for nitrosocaptopril, did not induce cGMP production in the porcine iris-ciliary body. ODQ, a guanylate cyclase inhibitor, shut down the production of cGMP after the administration of nitrosocaptopril and SNP. The guanylate cyclase activators YC-1 and atriopeptin III increased cGMP dose-dependently. CONCLUSIONS: In this novel tissue incubation method, several NO donors and guanylate cyclase activators increased cGMP production in the porcine iris-ciliary body. This method can be used to screen new molecules in terms of cGMP production, since the ciliary body is important in lowering intraocular pressure.

Animals↗

PubMed1983

Neurilemmoma of the ciliary body: report of a case.

A case of ciliary body neurilemmoma is described. This neoplasm is extremely rare in the uveal tract and has been reported only once in the ciliary body. After extensive clinical studies of the rapidly growing tumour enucleation was performed. Subsequent histological examination showed typical features of highly vascular benign neurilemmoma. The main clinical and pathological features are reported and diagnostic problems are discussed.

Adult↗

PubMed1996

Biochemical studies on the secretion of glycoproteins by isolated ciliary body of rabbits.

The contribution of the ciliary body to the origin of vitreous proteins was investigated in rabbits by incubating explants of this eye component under novel conditions. At the end of incubations for up to 21 h, the tissues were processed histologically and were shown to be in an excellent state of morphological preservation. When radioactive amino acids and fucose were added to the culture medium, protein and glycoprotein synthesis and secretion were detected using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) plus fluorography. The origin of these secretory products was traced by autoradiography to the ciliary epithelium. When samples of vitreous bodies - injected intravitreally with the same radioactive precursors - were run beside samples of the tissue culture media, comigration of at least 8 radioactively labelled bands including the one previously identified as transferrin was detected. This indicates that some vitreous proteins may be secreted by the ciliary body and that cultures of explants of ciliary body-iris are useful tools for studies on vitreous protein secretion.

Amino Acids↗

PubMed1999

Ciliary body melanocytoma with anterior segment pigment dispersion and elevated intraocular pressure.

PURPOSE: To discuss a case in which melanocytoma of the ciliary body presented with widespread pigment dispersion and elevated intraocular pressure (IOP). METHODS: A 64-year old woman presented with increased IOP and persistent anterior segment inflammation in her right eye. She had undergone a trabeculectomy for uncontrolled IOP before presentation. Slit-lamp examination, gonioscopy, and ultrasound biomicroscopy revealed a ciliary body mass with extension into the subconjunctiva in addition to widespread pigmentary dispersion in the anterior segment. Enucleation of the right eye was performed for histopathologic evaluation, as a diagnosis of ciliary body melanoma was made on clinical examination. RESULTS: Histopathologic findings were diagnostic of a melanocytoma of the ciliary body with necrosis and focal malignant transformation with extension of melanocytoma cells and melanophages into the subconjunctival space, trabecular meshwork, and anterior chamber angle. CONCLUSION: Melanocytoma of the ciliary body is a rare intraocular tumor that may present with pigment dispersion and secondary elevated IOP. Careful examination of the anterior segment is imperative in such cases.

Anterior Eye Segment↗

PubMed2000

Plaque radiotherapy for management of ciliary body and choroidal melanoma with extraocular extension.

PURPOSE: To report the results of plaque radiotherapy of ciliary body and choroidal melanoma with extraocular extension. METHODS: This retrospective study of 17 eyes of 17 patients with ciliary body and choroidal melanoma demonstrated extraocular extension that was clinically evident but less than 3 mm in thickness. In 14 eyes, the extraocular extension was located anteriorly and in three posteriorly. The outcome of plaque radiotherapy in terms of intraocular and extraocular tumor responses and the development of metastasis were analyzed. RESULTS: At a median follow-up of 63 months (range, 23 to 164 months) after plaque radiotherapy, all patients showed control of both the intraocular and extraocular components of ciliary body and choroidal melanoma. In no case did the intraocular or extraocular portion of the tumor relapse. The initial median thickness of the intraocular component was 4.9 mm, and the final median thickness was 2.4 mm. The initial median thickness of the extraocular component was 2.0 mm, and the final median thickness was 1.0 mm. The initial median basal diameter of the extraocular component was 3.5 mm, and the final median basal diameter was 2.0 mm. Of 17 patients, 11 (10 with anterior and one with posterior extraocular extension) showed partial regression in base and thickness of the extraocular extension, and in six there was little or no change. In those with anterior extrascleral extension, the sclera remained intact without clinically observable necrosis, and the scleral fibers were gradually more visible as the tumor regressed. Three patients (18%) died of metastatic melanoma at a median interval of 38 months after plaque radiotherapy. CONCLUSIONS: Plaque radiotherapy appears to be a reasonable treatment option for selected cases of ciliary body and choroidal melanoma with clinically visible extraocular extension less than 3 mm in thickness.

Adult↗

PubMed1989

Glutathione S-transferase of bovine iris and ciliary body: characterization of isoenzymes.

Five forms of glutathione (GSH) S-transferase (GST) having catalytic activities towards a variety of xenobiotics were present in bovine iris-ciliary body. In contrast to that in lens, cornea, and retina, GST isoenzymes belonging to all the three classes (alpha, mu and pi) were present in iris as well as in the ciliary body. GST isoenzymes of iris-ciliary body had pI values of 8.7, 7.4, 7.0, 6.6, and 6.0. GST 8.7 and GST 7.4 were apparent homodimers of 27,000 and 22,500 Mr subunits, respectively. GST 8.7 cross-reacted only with antibodies raised against the alpha class GST of human liver and GST 7.4 cross-reacted with the antibodies raised against GST pi of human placenta. GST 7.0 and 6.6 were heterodimers of Mr 26,500 and 25,000 subunits and both these subunits cross-reacted with the antibodies raised against the mu class human GST. Iris-ciliary body contained both, GSH peroxidase I and GSH peroxidase II activities and in this respect also, they differ from lens, cornea, and retina each of which have only one of these two activities. The presence of several GST isoenzymes belonging to all the three major classes and both GSH peroxidase I and II activities in iris-ciliary body may be important for the detoxification of oxidants and xenobiotics in order to prevent their infiltration in aqueous humor.

Animals↗

PubMed1992

[Effects of prostaglandin E2 on intraocular pressure, anterior chamber depth and blood flow volume of the iris and the ciliary body in rabbit eyes].

The effects of prostaglandin E2 (PGE2) on intraocular pressure (IOP), anterior chamber depth, and blood flow volume of the iris and the ciliary body of albino rabbits were investigated. Swelling and marked capillary dilatation of the ciliary body were observed after topical application of PGE2. IOP increased immediately by 200 micrograms, 400 micrograms, and 1,000 micrograms of PGE2, reached a peak within 30 minutes; then decreased gradually. The anterior chamber depth decreased only at 5 and 10 minutes after 1,000 micrograms of PGE2. The blood flow volume of the iris and the ciliary body immediately increased, and kept it up for 3 hours. Changes of IOP may be associated with an increase of blood flow attendant upon capillary dilatation of the ciliary body, and an increase of aqueous outflow due to breakdown of the blood-aqueous barrier. In addition to morphological and functional changes of the ciliary body, further factors which promote vitreous volume expansion may play an essential part in the development of malignant glaucoma.

Animals↗

PubMed1979

The transport of para-aminohippuric acid by the ciliary body and by the iris of the primate eye.

Para-aminohippuric acid (PAH) accumulates against a concentration gradient in the ciliary body and independently in the iris of the rhesus monkey eye. This accumulation is inhibited by incubation of 0 degrees C and shows saturation kinetics in both tissues. Cyanide, ouabain, dinitrophenol, iodopyracet, and probenecid effectively depress PAH uptake in both tissues, but anaerobic incubation conditions have little effect on uptake in either tissue. The washout of preaccumulated PAH occurs 2.5 times faster from the iris than from the ciliary body. The effects on washout of 10(-4)M PAH, 0 degrees C, and 10(-5)M dinitrophenol are consistent with washout occurring by a diffusional mechanism in both tissues, with some reaccumulation occurring in the ciliary body only. In addition, nonsaturable uptake of PAH, studied in both tissues under high PAH concentrations, also occurs significantly faster in the iris than in the ciliary body. The kinetic analysis of active PAH uptake in both tissues is discussed in terms of initial uptake and in terms of a steady-state model. This steady-state model compensates for some technical problems in applying in vitro incubation techniques to primate tissues and also includes a correction for the additional exchange processes that affect the two tissues differently. Results of the kinetic analysis suggest that, at least to an order of magnitude, iris uptake is significant with respect to ciliary body uptake.

Aminohippuric Acids↗

PubMed1993

Prostaglandin receptors coupled to adenylyl cyclase in the iris-ciliary body of rabbits, cats and cows.

Stimulation of adenylyl cyclase by prostaglandin (PG) receptor agonists was examined in the iris-ciliary body of rabbits, cats and cows. Iris-ciliary bodies were incubated with or without agonists in Krebs pyruvate buffer containing protease and cyclooxygenase inhibitors. The formation of cAMP in a 15-min period in response to the agonists was measured. In the rabbit iris-ciliary body, all PG receptor agonists at concentrations of 0.062-10.0 microM with the exception of sulprostone stimulated adenylyl cyclase. In this species, 17-phenyl trinor PGE2 and PGF2 alpha stimulated adenylyl cyclase but only at high concentrations (> 5 microM). The order of potency of the agonists was dimethyl PGE2 > PGE2 > 11-deoxy PGE1 = PGD2 > iloprost > PGF2 alpha. The DP receptor antagonist BWA868C had no effect on EP agonist responses, indicating that PGE2, dimethyl PGE2 and 11-deoxy PGE1 were not stimulating DP receptors. In the cat, PGE2, dimethyl PGE2 and 11-deoxy PGE1, were all equally potent in stimulating adenylyl cyclase. The order of potency in the cow was PGE2 > dimethyl PGE2 > 11-deoxy PGE1. However, PGD2, iloprost, 17-phenyl trinor PGE2 and PGF2 alpha were inactive in this species. The results of this study indicate that EP receptor agonists stimulate adenylyl cyclase in the iris-ciliary body of the three species; stimulation by other agonists depends on the species. In the rabbit, the EP2 receptor subtype appears to predominate; such a predominance of EP2 receptors was not observed in the cat and cow.

Adenylyl Cyclases↗

PubMed2003

Transepithelial short circuit currents in human and porcine isolated ciliary bodies: effect of acetazolamide and epinephrine.

BACKGROUND: To investigate in human and porcine isolated ciliary bodies the effect of acetazolamide and epinephrine on ciliary transepithelial ionic currents (a parameter linked to aqueous humor production). MATERIAL AND METHODS: Isolated ciliary bodies were mounted in a Ussing-type chamber to measure transepithelial potential difference (PD) and short circuit current (Isc) before and after exposure to either 100 micro M acetazolamide or 10 micro M epinephrine. RESULTS: In humans (N = 27), baseline PD was 1184 +/- 100 micro V (negative on the non-pigmented epithelial [NPE] side) and Isc 19.9 +/- 1.5 micro A/cm 2. Acetazolamide (N = 7 - 8) decreased Isc (NPE side: 8.4 +/- 1.1 micro A/cm 2; pigmented epithelial [PE] side: 7.4 +/- 0.9 micro A/cm 2) while epinephrine (N = 6) increased Isc only on the NPE side (9.9 +/- 0.8 micro A/cm 2). In pigs, baseline PD was in some preparations negative (862 +/- 84 micro V, N = 18) and in others positive (814 +/- 81 micro V, N = 10) on the NPE side with Isc 15.6 +/- 1.6 micro A/cm 2 and 16.3 +/- 2.6 micro A/cm 2, respectively. In all preparations, acetazolamide (N = 6 - 7) decreased Isc (NPE side: 6.1 +/- 0.6 micro A/cm 2; PE side: 4.8 +/- 0.3 micro A/cm 2) while epinephrine (N = 8) increased it only on the NPE side (10.5 +/- 0.6 micro A/cm 2). CONCLUSIONS: To our knowledge, this is the first time that this methodology is applied to measure transepithelial ionic currents in isolated human and porcine ciliary bodies. This method could be used to test drugs modulating aqueous humor production.

Acetazolamide↗

PubMed2002

[Complications of a voluminous congenital ciliary body cyst].

BACKGROUND: Multiple cysts of iris and ciliary body may cause many complications such as acute or chronic angle closure glaucoma. PATIENT: We present a boy with multiple congenital cysts of the iris pigment epithelium and a voluminous cyst of the unpigmented ciliary body epithelium of the right eye. This resulted in lenticular astigmatism, concomitant strabismus divergens and subsequently to anisometropia. The voluminous cyst (8 x 12 mm in diameter) was folded around the lens, reached the optic axis and resulted in displacement of the lens and contact between the iris and the corneal endothelium from 6.30 to 11. After puncture and partial resection of the cyst at the age of 8 months the boy developed a subcapsular multivesicular cataractic clouding of the temporal lens and a progredient myopia (up to - 14.0/- 2.0/0 degrees ); in contrast the left eye was hyperopic (+ 3.5/- 3.75/0 degrees ). The lens was subluxated superonasally due to congenital damage of the zonular fibres. Because development of visual acuity seemed limited by these determinants (20/200 at the right eye), cataract surgery with posterior capsulorhexis, anterior vitrectomy, and implantation of a capsular tension ring and posterior chamber intraocular lens was performed at the age of nearly five. Actually, there is an orthotropia, best corrected visual acuity in the distance of 20/32 in the right and 20/20 in the left eye; binocular vision is somewhat restricted. CONCLUSION: Usually congenital cysts are clinically not very relevant; occasionally surgical intervention is required to ensure adequate development of visual acuity.

Anisometropia↗

PubMed2004

3H-Noradrenaline release from mouse iris-ciliary body: role of presynaptic muscarinic heteroreceptors.

Sympathetic neurotransmitter release and its modulation by presynaptic muscarinic heteroreceptors were studied in mouse iris-ciliary bodies. Tissue preparations were preincubated with (3)H-noradrenaline and then superfused and stimulated electrically. Firstly, experimental conditions were defined, allowing study of presynaptic sympathetic inhibition in mouse iris-ciliary body. If tissue was stimulated four times with 36 pulses/3 Hz, tritium overflow peaks were reliably and reproducibly measured. As expected, these stimulation conditions led to marked alpha(2)-autoinhibition as indicated by the release-enhancing effect of the alpha(2)-antagonists phentolamine and rauwolscine. To ensure autoinhibition-free (3)H-noradrenaline release, which is optimal for studying presynaptic sympathetic inhibition, alpha(2)-receptors were blocked in all subsequent experiments. Under these conditions, evoked tritium overflow was almost completely abolished in the presence of the sodium channel blocker tetrodotoxin, indicating a neuronal origin of (3)H-noradrenaline release. Secondly, muscarinic inhibition of (3)H-noradrenaline release was characterized using the conditions described above (36 pulses/3 Hz; phentolamine 1 muM and rauwolscine 1 muM throughout). The muscarinic receptor agonist oxotremorine M decreased evoked tritium overflow in a concentration-dependent manner with an IC(50) of 0.33 muM and maximal inhibition of 51%. The concentration-response curve of oxotremorine M was shifted to the right by the muscarinic antagonists ipratropium and methoctramine, whereas pirenzepine was ineffective. The observed rank order of antagonist potencies, ipratropium > methoctramine > pirenzepine, which is typical for the M(2) subtype, indicates that presynaptic muscarinic receptors on sympathetic axons of mouse iris-ciliary bodies are predominantly M(2). Finally, inhibition of (3)H-noradrenaline release by endogenously secreted acetylcholine was investigated. Longer pulse trains, 120 pulses/3 Hz and 600 pulses/5 Hz, were used and the cholinesterase inhibitor physostigmine was added to the superfusion medium to increase synaptic levels of endogenous acetylcholine. Under these conditions, ipratropium approximately doubled the evoked overflow of tritium, indicating that endogenously released acetylcholine can activate presynaptic muscarinic heteroreceptors. In conclusion, the present experiments establish measurement of the electrically induced release of (3)H-noradrenaline from mouse iris-ciliary bodies. As in other species, noradrenaline release in this preparation was subject to presynaptic muscarinic inhibition. Our results also indicate that the presynaptic muscarinic receptors on sympathetic axons in mouse iris-ciliary body are predominantly M(2). Moreover, these receptors can be activated by both exogenous agonists and endogenously released acetylcholine and, hence, may operate physiologically in the interplay between the parasympathetic and sympathetic nervous system.

Animals↗

PubMed2003

Expression of estrogen receptor alpha and 17beta-hydroxysteroid dehydrogenase 4 in the ciliary body.

PURPOSE: To investigate the expression and distribution of estrogen receptor alpha (ERalpha) and 17beta-hydroxysteroid dehydrogenase 4 (HSD4) in bovine and monkey ciliary body. METHODS: Immunohistochemical study was employed to investigate the expression of ERalpha and 17beta-HSD4. To detect ERalpha and 17beta-HSD4 transcripts, reverse transcription-polymerase chain reaction (RT-PCR) was used. RESULTS: In bovine and monkey ciliary body, the staining of the anti-ERalpha antibody was distributed in nonpigmented epithelium, and was not detectable in pigmented epithelium. Vessels in the stroma were also stained. The expression of 17beta-HSD4 was observed in nonpigmented and pigmented epithelium. RT-PCR revealed that the transcripts of ERalpha and 17beta-HSD4 were expressed in monkey ciliary body. CONCLUSIONS: This study provides evidence for the presence of ERalpha and 17beta- HSD4 in the ciliary body. The presence of ERalpha and 17beta-HSD4 suggests that estrogen may have important functions in the ciliary body.

17-Hydroxysteroid Dehydrogenases↗