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PubMed2002

Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor.

We have determined the agonist activity of a number of natural prostaglandins and prostaglandin analogs at the FP prostaglandin receptor cloned from a human ciliary body cDNA library using phosphoinositide (PI) turnover assays. Travoprost acid (EC50 = 3.2 +/- 0.6 nM) was the most potent agonist in these cells followed by bimatoprost free acid (17-phenyl-trinor PGF2alpha; EC50 = 5.8 +/- 2.6 nM), fluprostenol (EC50 = 6.1 +/- 1.5 nM), and latanoprost free acid (PHXA85; EC50 = 54.6 +/- 12.4 nM) which was 17-fold weaker (p < 0.001) than travoprost acid. Unoprostone and S-1033 were significantly (p < 0.001) weaker than travoprost acid. The amide prodrug, bimatoprost (EC50 = 694 +/- 293 nM), activated this FP receptor with an intermediate potency. The isopropyl ester prodrugs, travoprost (EC50 = 42.3 +/- 6.7 nM), latanoprost (EC50 = 126 +/- 347 nM) and unoprostone isopropyl ester (EC50 = 9,100 +/- 2,870 nM), also exhibited FP agonist activity. However, other compounds such as PGI2, bradykinin, histamine, and serotonin were inactive. The agonist activities of bimatoprost, unoprostone (UF-021), fluprostenol and acids of travoprost and latanoprost were antagonized by AL-8810 (11beta-fluoro- 15-epi-15-indanyl-PGF2alpha), an FP-receptor-selective antagonist (Ki = 1.0 - 2.1 microM; n = 3). These studies have demonstrated, for the first time, agonist activities of the currently known and marketed ocular hypotensive prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor.

Amides↗

PubMed1989

[Monocular near-point accommodation and the blood supply to the ciliary body of the amblyopic eye in schoolchildren with concomitant strabismus].

Visual acuity, the character of fixation, the angle of deviation, refraction, monocular determination of accommodation and blood supply of the ciliary body have been studied in 50 schoolchildren (100 eyes) with convergent strabismus and amblyopia of various degree. Children with amblyopia of high and moderate degrees have shown a sharp fall or absolute absence of the positive part of relative accommodation and reduced blood supply of the ciliary body. Between the mentioned indices and degree of amblyopia there exists a positive connexion.

Accommodation, Ocular↗

PubMed1992

Extracellular matrix in aged human ciliary body: an immunoelectron microscope study.

Tissue from nine human eyes (ages 52-78 yr) was used to investigate the fine structural distribution of collagens I-VI and laminin in the ciliary body using the immunogold antibody labeling technique. The anterior segments of the specimens were normal, and the eyes were removed in treatment of choroidal melanoma. The basement membranes of the ciliary epithelium contained collagens I, III, and IV. Laminin was in greater concentration in the outer part of the nonpigmented epithelial basement membrane, and the distribution suggested a washout effect. The zonular apparatus labeled intensely with laminin. In contrast, laminin was not present in the basement membrane of the myocytes in the ciliary body. These cells were sheathed in a basement membrane that contained types I, III, and IV collagen. Plaque-like structures of slightly different morphology (a, filamentous; b, granular; c, amorphous) were found in the tendinous insertions, and subtypes a and b were strongly labeled with laminin. The basement membranes of the vessels contained types I and IV collagen, but laminin labeling was inconclusive. The major finding was that the lamina densa in the basement membranes of various sites labeled for collagens I, III, and IV. Striated collagen fibrils in the stroma were labeled for types I and III. Collagen subtypes V and VI were not identified in significant quantity in any of the regions examined.

Aged↗

PubMed1989

[Accommodative hyperemia of the ciliary body as one of the pathogenetic factors in myopia].

Thermometry of 40 eyes before and after visual work at near with different correction of ametropia and tonography of 20 eyes with progressive myopia and 20 eyes with stationary myopia conducted before and after 15-minute reading load under full correction have revealed that visual work at near is accompanied by working hyperemia of ciliary body (rise of temperature in the anterior segment of the eye ball) and hyperproduction of intraocular fluid. In eyes with stationary myopia, hyperproduction is fully compensated by improvement of aqueous outflow from the eye. In eyes with progressive myopia, ophthalmic hypertension takes place because of insufficient improvement of the outflow facility coefficient. It is likely that working hyperemia of the ciliary body and hyperproduction of intraocular fluid under conditions of visual work at near can be realized as a factor of myopization of the human eye in case of a certain predisposition: in eyes with a not fully formed angle of the anterior chamber or in eyes with anomalous development of the angle.

Accommodation, Ocular↗

PubMed1999

Ciliary body detachment caused by capsule contraction.

A 74-year-old woman developed capsule contraction associated with hypotony and choroidal effusion 18 months after uneventful phacoemulsification with 3-piece poly(methyl methacrylate) intraocular lens implantation. Ultrasound biomicroscopy revealed ciliary body detachment and stretched zonules. A radial neodymium: YAG anterior capsulotomy was performed, resulting in the resolution of the ciliary body detachment and choroidal effusion as well as in normal intraocular pressure over 4 days.

Aged↗

PubMed1996

Transient activation of K+ channels by carbachol in bovine pigmented ciliary body epithelial cells.

The action of carbachol (CCh) on isolated pigmented ciliary epithelial cells was examined using whole cell patch-clamp recording. Application of 100 microM CCh caused transient, occasionally oscillatory, increases in the inward and outward currents, followed by a long-term decrease in both currents. Caffeine produced transient responses similar to those of CCh. The responses to CCh were blocked by the muscarinic receptor antagonist atropine and the inositol 1,4,5-trisphosphate receptor blocker heparin (200 micrograms/ml in patch pipette). Manipulation of the internal ionic concentrations indicated that only K+ conductances were affected by CCh. Changing intracellular Ca2+ concentration ([Ca2+]i) with the calcium ionophore ionomycin demonstrated that both the inward rectifier K+ current and the outward current exhibited Ca2+ dependence. There was no Cl- current stimulated either directly by CCh or indirectly by modulators of [Ca2+]i, and any Cl- currents present arose from osmotic effects. In the short term, muscarinic stimulation will activate K+ channels by causing a transient increase in [Ca2+]i. This effect only lasts for 1-5 min, however, and, in the long term, the conductance decreases below its original level. The effect of such a transient increase in [Ca2+]i on secretion would be complex, involving effects on gap junction communication between the pigmented and nonpigmented cell layers and the activation state of Cl- channels in the nonpigmented cells. This complexity probably accounts for the variable reports of the effects of muscarinic stimulation of the ciliary body in vivo.

Animals↗

PubMed1979

Scleral buckles and rotation of the ciliary body.

Angle closure glaucoma is a well-known complication of scleral buckling and it is of particular interest when it occurs in eyes with previously normal angles. Forward rotation of the ciliary body about the scleral spur has been postulated as one possible mechanism for such angle closure. Large buckles were used in macaque rhesus monkeys and histopathologic examination indicated rotation of the ciliary body about the scleral spur as the cause of angle closure. Pupillary block was not present and large choroidal detachments were not needed to produce the observed closure. The exaggerated buckles used do not allow these monkeys to serve as a clinical model and great caution is stressed in making clinical extrapolations.

Animals↗

PubMed1990

Inhibitory effects of neuropeptide Y on sympathetic neurotransmission in the rabbit iris-ciliary body.

Neuropeptide Y (NPY, 1-300 nM) mediated a concentration-dependent inhibition of field stimulation-evoked [3H]norepinephrine (NE) overflow from the isolated, superfused rabbit iris-ciliary body. At equimolar concentrations (100 nM), the homologous neuropeptide peptide YY (PYY) mimicked the effects of NPY, whereas pancreatic polypeptide (PP) and the C-terminal fragment of NPY did not modify [3H]NE release. NPY-induced inhibition of [3H]NE release was unaffected by pretreatment of tissues with atropine (100 nM) plus yohimbine (100 nM) and was non-additive with the maximal prejunctional effects of carbamycholine or clonidine, indicating that NPY acts independently of prejunctional muscarinic or alpha 2-adrenergic receptor activity to reduce [3H]NE overflow. It is concluded that NPY is a specific, potent modulator of adrenergic neurosecretion in the rabbit iris-ciliary body. These findings confirm the role of NPY as a co-transmitter at ocular sympathetic neuroeffector junctions, either mimicking or augmenting the actions of endogenously released norepinephrine.

Animals↗

PubMedDate not supplied

Functional and morphological differentiation of nonpigmented ciliary body epithelial cells grown on collagen rafts.

We have examined the effect of alteration in cell shape on promoting differentiated morphology and physiology in cultured nonpigmented epithelial cells from the ciliary body. We have grown pure populations of nonpigmented cells on collagen gels released from the culture dish to create collagen rafts. Shortly after the gels were detached, the cells shrank in diameter and increased in height while they contracted the gel. Concurrently, the actin cytoskeleton reorganized to the cell cortex as found in vivo. After this differentiated morphology developed, large changes in intracellular Ca2+ could be elicited by simultaneous activation of acetylcholine and epinephrine or acetylcholine and somatostatin receptors as seen in intact tissue. Explant cultures of isolated nonpigmented cell layers maintained their actin distribution and also showed synergistic Ca2+ increases. Spread cells, grown on rigid substrates, had a disorganized cytoskeleton and rarely showed synergism. These data suggest that the mechanism underlying synergistic Ca2+ responses in the ciliary body is functional in nonpigmented cells grown on collagen rafts. In addition, this pathway appears to be sensitive to the disposition of the cell's cytoarchitecture.

Acetylcholine↗

PubMed1998

[Immunohistochemical studies on wholemounts of the cornea and iris-ciliary body after corneal transplantation].

OBJECTIVE: To study the phenotype of the cells involved in the pathogenesis of allograft rejection after corneal transplantation. METHODS: Wholemounts of the cornea and iris-ciliary body were isolated and prepared from normal rats and those after penetrating corneal transplantation. Immunohistochemical stainings were carried out on these wholemounts using monoclonal antibodies to CD3 (T cell), CD4 [T-helper (Th) cell], CD8 [T-suppressor (Ts) cell], macrophages, dendritic cells, B lymphocytes, major histocompatibility complex (MHC) class II antigen and transforming growth factor-beta (TGF-beta). RESULTS: All the cells mentioned above except B lymphocytes were positive and present in a small number in the peripheral cornea and limbus of normal rats. A massive influx of CD3, CD4, CD8 positive cells, macrophages, dendritic cells, MHC class II and TGF-beta positive cells not only into cornea but also into the iris was observed 7 days after allograft corneal transplantation. Whereas no B cell was found in the allograft. Such a cellular response was not found in the rats in which corneal transplantation with autologous cornea was performed. CONCLUSION: T cells, Th cells, Ts cells, macrophages, dendritic cells, MHC class II positive cells and TGF-beta positive cells are involved in the pathogenesis of corneal allograft transplantation. The involvement of the iris and ciliary body may promote or aggravate the allograft rejection.

Animals↗

PubMed1994

Dihydropyridine-sensitive Ca2+ spikes and Ca2+ currents in rabbit ciliary body epithelial cells.

Intracellular microelectrode and whole-cell patch-clamp recordings were used to investigate a Ba(2+)-induced regenerative depolarization and its underlying Ba2+ current in the ciliary body epithelial cells of the rabbit eye. Exposure of these epithelial cells to 4-10 mmol l-1 Ba2+ depolarized the membrane potential and caused the generation of one or more spikes, before the membrane potential reached a steady-state level. The spikes, but not the slow phase of depolarization, could be blocked with Co2+ (2 mmol l-1), Gd3+ (25 mumol l-1), La3+ (20 mumol l-1), Cd2+ (10 mumol l-1), verapamil (30 mumol l-1) and nifedipine (1 mumol l-1). Tetrodotoxin at 100 nmol l-1 had no effect. In the absence of Na+, but in the presence of external Ba2+, step depolarization of the membrane potential activated an inward current that could be blocked with Co2+ (2 mmol l-1), Cd2+ (10 mumol l-1) and nifedipine (1 mumol l-1), but not with Ni2+ (50 mumol l-1) or omega-conotoxin (1-10 mumol). This inward current could be enhanced with the dihydropyridine agonist (+/-)BAY K 8644 (1 mumol l-1). The inactivation characteristics of the inward current (v1/2 = -38.7 mV, k = 12.6 mV) is most like that seen in neurons. These findings indicate that the epithelial cells of the ciliary body possess dihydropyridine-sensitive, voltage-activated Ca2+ channels.

Action Potentials↗

PubMed1976

Organic cation uptake in vitro by the rabbit iris-ciliary body, renal cortex, and choroid plexus.

The uptake in vitro of radioactively labeled test substances was studied in tissues from albino rabbits. Choroid plexus, slices of outer renal cortex, and iris-ciliary body were incubated in a K-rich medium containing one of the cations 14C-Emepronium (Cetiprin), 14C-tetraethylammonium, 14C-choline, or 125I-o-iodobenzyltrimethylammonium and sometimes the anions 131I-o-iodohippurate and 125I-iodipamide. Choroid plexus and renal cortex accumulated all test substances, some to very high tissue-medium ratios. The iris-ciliary body preparation accumulated the anions well but the organic cations only weakly. The only convincing uptake was that of Emepronium. The affinity of this uptake system seemed to be similar to that in the kidney, half-saturating around 10(-4)M Emepronium.

Animals↗

PubMed1989

Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists.

Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi.

Adenine↗

PubMed1998

Long-term survival in choroidal and ciliary body melanoma after enucleation versus plaque radiation therapy.

OBJECTIVE: This study aimed to determine whether the long-term melanoma-specific mortality rate of patients with a primary choroidal or ciliary body melanoma treated by enucleation is appreciably lower than that of similar patients treated by plaque radiation therapy. DESIGN: Retrospective, nonrandomized, comparative clinical trial. PARTICIPANTS: A previously reported group of 237 patients, 140 treated by enucleation and 97 treated by cobalt-60 (Co-60) plaque between May 1976 and June 1980, and a residual group of 122 patients, 51 treated by enucleation and 71 treated by Co-60 plaque, were identified by variable-by-variable range matching. INTERVENTION: Primary treatment by enucleation or Co-60 plaque radiation therapy was performed. MAIN OUTCOME MEASURES: Melanoma-specific mortality and duration of post-treatment survival were measured. RESULTS: The melanoma-specific mortality rate was substantially worse in the original enucleation subgroup over the entire 15-year follow-up interval; however, differences in baseline prognostic factors between the subgroups are likely to explain the difference in survival curves. After elimination of patients with nonoverlapping values of individual clinical variables to adjust for recognized intergroup differences at baseline, there was no significant or clinically important difference in the 15-year mortality curves of the residual subgroups. The relative rate ratio for the treatment effect in the residual patients was 0.97 (95% confidence interval, 0.51-1.86). There was no late downturn in the survival curve of the plaque-treated patients or late crossing of the curves. CONCLUSION: A large difference in survival between equivalent groups of patients with primary choroidal or ciliary body melanoma treated by enucleation versus plaque radiation therapy appears to be unlikely.

Adult↗

PubMed1979

[Slow potentials of the receptive field of the ciliary body and their relationship to regulation of intraocular pressure].

Spontaneous slow potentials with amplitude ranging from 25 mcV to 1.3 mV and wave duration from 600 to 6000 msec was recorded in the receptive area of the ciliary body. The same potentials persisted even 15--20 min after the death of animal in the enucleative eye as well as in the isolated preparation of the ciliary body with sclera. The rise of the intraocular pressure up to 30--35 mm Hg augments the potentials whereas further rise up to 45 mm Hg and more suppresses them. Electrostimulation acts in a similar way: square pulses of 25 mcV augment the potentials' amplitude whereas the 250 mcV pulses reduce it.

Animals↗

PubMed1982

[Adenoma of the ciliary body (author's transl)].

An adenoma of the non-pigmented ciliary body was removed locally; 15 years later the eye was enucleated. The globe contained a small tumor with similar histological features but invasive growth.

Adenoma↗

PubMed1990

Potentiation of norepinephrine secretion by angiotensin II in the isolate rabbit iris-ciliary body.

The prejunctional effects of angiotensin II (AII) on stimulation-evoked secretion of 3H-norepinephrine (3H-NE) were investigated by in vitro methods in isolated, superfused rabbit iris-ciliary body preparations. AII (0.1-10 nM) concentration-dependently enhanced the field- stimulated release of 3H-NE (EC50 = 0.1 nM), nearly doubling evoked neurotransmitter release with no apparent effect on spontaneous 3H-NE efflux. The response to 1 nM AII was abolished by the selective AII receptor antagonist saralasin [( Sar1,Val5, Ala8]-angiotensin II; 500 nM), which alone did not modify 3H-NE overflow. AII-mediated effects on neurosecretion were partially additive to those of forskolin and were not potentiated by phosphodiesterase inhibition, suggesting that AII utilizes a mechanism other than increased cAMP synthesis to facilitate neurotransmitter release. AII also strongly enhanced calcium ionophore (A23187)-induced 3H-NE release in iris-ciliary body segments, indicating that AII can modulate calcium-dependent exocytosis at step(s) distal to calcium influx. These results demonstrate that sympathetic nerves in the rabbit eye contain prejunctional, facilitatory AII receptors, and support the possible involvement of the renin-angiotensin system in regulation of ocular sympathetic neurotransmission in vivo.

1-Methyl-3-isobutylxanthine↗

PubMed1991

Halogenated inhalation anesthetic agents decrease transepithelial electrical measurements across the isolated iris-ciliary body.

Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body (I-CB) to study the direct effects of halogenated inhalation anesthetic agents on the ciliary epithelium. Addition of either halothane, enflurane, or isoflurane to the control 95% O2:5% CO2 gas mixture resulted in a dose-dependent decrease in the short-circuit current (SCC) and potential difference (PD). This response was reversible after the anesthetic gas was discontinued. Pretreatment with either alpha-adrenergic or beta-adrenergic antagonists (phentolamine or timolol) had no effect on the halothane-induced decrease in SCC. Delivery of the analgestic gas N2O did not alter baseline electrical measurements across the isolated I-CB.

Analysis of Variance↗