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Leiomyoma in the posterior choroid: a case report.

Smooth muscle tumor of the uveal tract is rare, and mostly located in the cilio-choroidal area. We report a unique case of posterior choroidal leiomyoma in a 27-yr-old man. Ophthalmoscopic examination disclosed an 11 mm-sized mass on the fundus two-disc diameters apart from the optic disc. With a suspicion of amelanotic melanoma, the globe was enucleated. The mass occupied the whole thickness of choroidal stroma beneath the pigmented retinal epithelium and composed of spindle cells arranged in intersecting fascicles. Immunohistochemical studies demonstrated immunoreactivities of the tumor cells for smooth muscle actin, desmin, and vimentin. Ultrastructurally, numerous intracytoplasmic filaments with fusiform focal densities, scattered segmental external laminae, subplasmalemmal densities, and pinocytic vesicles were noted. The leiomyoma in this case had several unusual features in that it was confined to the posterior choroid with no relation to the ciliary body, occupied the whole stroma of the choroid instead of suprauveal location, and occurred in a young male. It is important to include choroidal leiomyoma in the differential diagnosis of choroidal tumors.

Actins↗

Fetal choroid plexus vascularization assessed by color flow ultrasonography.

We investigated the development of intracranial vascularization in the human fetus, with particular emphasis on the choroid plexus. The fetal brain was visualized in 102 patients with healthy pregnancies between 9 and 16 weeks' gestation. Imaging was done transvaginally except in the pregnancies of longer duration with unfavorable fetal positions. Color flow imaging was used to identify vessels in the cranium and within the choroid plexus. Pulsed Doppler signals were obtained from an internal carotid-middle cerebral artery and from a choroid plexus vessel. The pulsatility index was calculated from the Doppler spectral envelope. A major cerebral vessel could be seen at 9 weeks' gestation. Choroid plexus vessels were first seen at 10 weeks 3 days. Visualization rates ranged from 35 to 75% for plexus vessels, and 65 to 100% for cerebral vessels. Visualization of choroid plexus vessels was maximal at 13 weeks. The pulsatility index for the cerebral arteries at this gestational period averaged 2.6 +/- 0.6. The result for the choroid plexus was 1.66 +/- 0.5. (P < 0.001). Visualization of the vessels of the choroid plexus increases and decreases as the gland develops and shrinks. This developmental period also is the time of active neurogenesis.

Adult↗

Constitutive expression of cyclooxygenase-2 (COX-2) in developing brain. A. Choroid plexus in human fetuses.

It is believed that prostanoids produced by COX-1 activity are essential for the physiological functions of tissues while those produced by COX-2 lead to various pathological changes in these tissues. Brain is an exceptional organ where in some neurons COX-2 mRNA and its protein are constitutively expressed. Since some prostaglandins may play an important role in the control of blood-brain barrier and cerebral blood flow the purpose of the present study was to examine the COX-2 expression in choroid plexus, which participate in the nutrition of brain parenchyma of human fetuses. Study was performed on 25 brains of human fetuses from 12 to 38 weeks of gestation. In light and electron microscopy characteristic developmental transformation of choroid morphology was observed. In young fetuses from 12 to 20 week of gestation epithelial cells of choroid plexus are cuboidal, contain large amount of glycogen storage and their nuclei are COX-2 immunopositive. From 25 week of gestation until term the amount of glycogen in the choroid plexus diminishes, some apical nuclei are shifted toward central parts of the cells and number of cytoplasm organelles increases. In these cells expression of COX-2 protein is located in cytoplasm but epithelial nuclei are immunonegative. Our results provided evidence that COX-2 is constitutively expressed in the developing human choroid plexus. Different localization of COX-2 in choroid epithelial cells suggests that this enzyme may play a different role in various periods of the choroid plexus development.

Choroid Plexus↗

Evaluation of leukocyte dynamics in choroidal circulation with indocyanine green-stained leukocytes.

PURPOSE: To develop a new method with which to visualize leukocytes moving through the choroidal vessels of pigmented animals and enable the evaluation of leukocyte dynamics in the choroidal microcirculation. METHODS: Pigmented rabbits and monkeys were used in this study. Leukocytes, collected by centrifugal separation of autologous blood, were stained with indocyanine green (ICG) dye. The ICG-stained leukocyte fluid was injected into the vein, and the fundus image was obtained with a scanning laser ophthalmoscope. The image was recorded on videotapes and analyzed with a personal computer-based image analysis system. RESULTS: In pigmented rabbits, fluorescent leukocytes moving in the choroidal circulation were clearly visible for more than 1 hour. In monkeys, distinct fluorescent dots were seen moving approximately 50 to 200 microm in the foveal avascular zone for more than 30 minutes after the injection of the ICG-stained leukocyte fluid. Dim fluorescent dots were seen moving in the fundus. Although the movement of these dim dots was difficult to trace, they seemed to be moving in the choroidal vessels. In the rabbits, the mean flow velocity of leukocytes moving without plugging was 0.48 +/- 0.14 mm/sec in the peripheral choriocapillaris. In the monkeys, the mean flow velocity of distinct fluorescent leukocytes without plugging was 2.45 +/- 0. 48 mm/sec in the posterior choroid. CONCLUSIONS: In pigmented rabbits and monkeys, this method allows visualization of leukocytes passing through the choroidal vessels and provides a new way to investigate, noninvasively and in vivo, leukocyte dynamics in the choroidal microcirculation.

Animals↗

Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects.

PURPOSE: There is evidence from animal studies that nitric oxide (NO) is a major determinant of ocular blood flow. In humans NO synthase inhibition reduces pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature are available yet. The goal of this study was to investigate the effects of NO synthase inhibition on human choroidal and ONH blood flow using laser Doppler flowmetry. METHODS: The study design was a randomized, placebo-controlled, double-masked, balanced three-way crossover. On separate study days 12 healthy male subjects received infusions of N:(G)-nitro-L-arginine (L-NMMA; either 3 mg/kg over 5 minutes followed by 30 microg/kg per minute over 55 minutes or 6 mg/kg over 5 minutes followed by 60 microg/kg per minute over 55 minutes) or placebo. The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured with laser Doppler flowmetry. In addition, laser interferometric measurement of fundus pulsation was performed in the macula to assess pulsatile choroidal blood flow. RESULTS: L-NMMA reduced all outcome parameters in the choroid and the ONH. The higher dose of L-NMMA caused a significant decrease in blood flow in the choroid (-26% +/- 9%; P: < 0.001) and the ONH (-20% +/- 16%; P: < 0.001) as evidenced from laser Doppler flowmetry and a significant decrease in fundus pulsation amplitude (-26% +/- 5%; P: < 0.001). CONCLUSIONS: These results indicate that NO is continuously released in human choroidal and ONH vessels.

Adult↗

Regulation of choroid development by the retinal pigment epithelium.

PURPOSE: The choroidal vasculature is essential for normal retinal function. However, mechanisms that control choroid development are unknown. In the present study, we provide evidence that the retinal pigment epithelium (RPE) plays an essential role in regulation of the choroid development in the mouse eye. METHODS: Transgenic mice that transiently express FGF9 in the embryonic RPE were generated. Postnatal eyes were analyzed by histology and in situ hybridizations. RESULTS: In the transgenic mice, most of the RPE was converted to neural retina. The choroid formed only in regions where patches of RPE were present. The choroid failed to develop in the absence of the RPE. CONCLUSIONS: The presence of the RPE appears to be required for choroid development, suggesting that molecular interactions between RPE and periocular mesenchyme are essential for melanocyte differentiation and vascular development in the choroid.

Animals↗

Melanocytoma of the choroid: angiographic and histopathologic findings.

A juxtapapillary choroidal melanocytoma that was clinically confused with a choroidal melanoma is described. The clinical examination of a 40-year-old female patient included ultrasonography, fluorescein, and indocyanine green angiography. Histopathologic and immunohistochemical study of the enucleated eye resulted in the identification of a markedly pigmented, 3.8 mm elevated choroidal melanocytic tumor observed nasally to the disk. A-scan ultrasonography showed a high initial spike with a low to medium internal reflectivity with decreasing amplitude. On fluorescein angiography, the tumor was surrounded by a rim of retinal pigment epithelium depigmentation with a well-defined comet-tail. The lesion was hypofluorescent in the early phases of the indocyanine green angiogram, but from the late venous phase appeared ill-defined hyperfluorescence. Histopathologic study revealed a juxtapapillary choroidal melanocytoma The pigmented tumor cells stained positive for HMB45 and vimentin but negative for S100, GFAP, NSE, and MNF116. No tumor cells stained positive for the proliferation marker Ki67. These findings conclude that choroidal melanocytoma may mimick choroidal melanoma. Abnormalities on fluorescein angiography may be a clinical hint to suspect a pigmented tumor different from a choroidal melanoma.

Adult↗

Contractility studies on isolated bovine choroidal small arteries: determination of the active and passive wall tension-internal circumference relation.

Studies on isolated choroidal arteries could help to understand the regulatory mechanisms in the choroidal circulation. The aim of the present study was therefore to assess whether contractility studies on isolated choroidal arteries were feasible and to determine the active and passive wall tension-internal circumference relation of these arteries. This relation is essential for reliable further pharmacodynamic studies on these vessels. Isolated choroidal arteries were mounted on a wire myograph for isometric tension recording. After the vessel was mounted, the L(100) (the circumference of the vessel at a transmural pressure of 100 mmHg) was determined. Then the passive and active wall tension-internal circumference relation of the choroidal vessels was obtained by stepwise increasing the internal circumference. The changes in the internal circumference were expressed as a percentage of L(100). After each increase in circumference, the passive tone (in a calcium free medium), the spontaneous tone (in a Krebs--Ringer bicarbonate solution) and the active tone (in a solution containing K(+) 120 mM and prostaglandin F(2 alpha) 30 microM) was measured. The passive tone of the vessel increased exponentially with the circumference of the vessel. Both the spontaneous tone and the active tone also increased when the vessel was stretched. They peaked when the internal circumference approached 90% of the L(100) and diminished again when the circumference was further increased. The peak value of the active tension curve averaged 2.24+/-0.47 Nm(-1) (n=10). The passive tension was 0.57+/-0.08 Nm(-1) (n=10) at this circumference. The peak value of the spontaneous tension curve averaged 0.37+/-0.08 Nm(-1) (n=10). It can be concluded that in vitro contractility studies on isolated choroidal arteries are feasible. The optimal length or preload of the choroidal arteries is attained when the internal circumference of the artery is set to 90% of the L(100).

Animals↗

[The changes over time in areas of abnormal choroidal staining in central serous chorioretinopathy].

PURPOSE: We discuss the permeability of the choroid in central serous chorioretinopathy (CSC). METHODS: Forty-eight eyes of 48 patients with active CSC and their fellow eyes were studied with indocyanine green angiography (IA). Abnormal choroidal stainings in the late phase were fed in to a computer and hyperfluorescent areas were summated. The hyperfluorescent area at the initial examination was compared with that at the second examination. The values obtained were compared with the clinical characteristics shown by ophthalmoscopic, fluorescein angiographic (FA), and IA findings. RESULTS: The abnormal choroidal staining during IA was observed in 90% of the affected eyes and 67% of the fellow eyes. The average abnormal staining area was larger in the affected eyes than in the fellow eyes and decreased over time in both affected and fellow eyes, but the decrease rate of the abnormal staining was higher in the affected eyes. In FA abnormal staining areas of the smokestack type were significantly smaller than those of the round-diffusion type. The range of abnormal choroidal staining was significantly smaller in the affected eyes treated with laser photocoagulation than in the eyes not treated without laser coagulation. CONCLUSIONS: We conclude that the range of abnormal choroidal staining is consistent with changes of activity in the course of CSC, that the malfunction of the retinal pigment epithelium and choroidal hyperpermeability mutually influence CSC and that the disappearance of serous detachment in the clinical course plays an important role in the improvement of choroidal permeability and the retinal pigment epithelium function.

Adult↗

[Electron microscopic study of choroid plexus in experimentally induced hydrocephalic dog (author's transl)].

Choroid plexus in experimentally induced hydrocephalic dogs according to the Wisniewski's method was examined by an electron microscope. Epithelial cell of the choroid plexus appeared in various deformation and formed a marked dilatation of extracellular spaces between apposed two cell membranes and at the basal interdigitation. Dilatation of the extracellular space was more pronounced at the stromal side of the epithelial layer. This finding might be due to anatomical specificities of apposed epithelial cell membranes and not only indicate a disturbance of the CSF secretion. According to the dilatation of extracellular space, apposed two epithelial cell membranes separated each other, however, at sites of intercellular junctions, adjacent cell membranes remained closely apposed. The dilated extracellular space at the basal site continued to the dilated intercellular space, while, no continuity was recognized between the dilated intercellular space and ventricular lumen. These extracellular speces appeared low electron density and showed little specific structure. No particular change was recognized in organelles in the epithelial cell, except increased pinocytotic vesicles in number. Stroma of the choroid plexus appeared edematous, that was, electron density was low and a few cellular and stromal elements were found. Capillary vessels showed almost normal structure. In hydrocephalic dogs also in normal one, Lanthanum infused into lateral ventricle precipitated on the surface of microvilli of choroid plexus epithelial cell. The Lanthanum, entered through ventricular end of intercellular space, was blocked to penetrate beyond the intercellular junction (zonula occludens) and any bit of the tracer was not found in the dilated extracellular space. The tracer was found neither in epithelial cell nor in stroma. These findings of tracer-study may indicate that the CSF absorption through the choroid plexus is not increased in chronic hydrocephalus. Consequently, the ultrastructural changes of the choroid plexus in chronic hydrocephalus, that is, enlarged extracellualr space, increased pinocytotic vesicles and edematous stroma, are thought to suggest a disturbance of CSF secretion from the choroid plexus.

Animals↗

Stimulation of somatostatin expression in developing ciliary ganglion neurons by cells of the choroid layer.

An important component of neuronal development is the matching of neurotransmitter expression with the appropriate target cell. We have examined how peptide transmitter expression is controlled in a simple model system, the avian ciliary ganglion (CG). This parasympathetic ganglion contains 2 distinct types of neurons: choroid neurons, which project to vasculature in the eye's choroid layer and use somatostatin as a co-transmitter with ACh, and ciliary neurons, which innervate the ciliary body and iris and use ACh but no known peptide co-transmitter. We have found that the earliest developmental stage in which neurons with somatostatinlike immunoreactivity (SOM-IR) are consistently found in vivo is stage 30 (embryonic day 6.5), a time shortly after the extension of neurites to targets in the eye's choroid layer. In cell culture, CG neurons expressed SOM-IR in co-culture with choroid cells, but not when cultured with striated muscle myotubes or with ganglion non-neuronal cells. No significant differences in neuronal survival or in ChAT activity were observed under these different co-culture conditions, which suggests that somatostatin expression is independently regulated. The stimulation of somatostatin expression was also specific in that other neuropeptides commonly found in autonomic neurons [neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP)] were not induced in the presence of choroid cells. The ability to stimulate SOM-IR was not contact dependent because a macromolecule of greater than or equal to 10 kDa in choroid-conditioned medium (ChCM) was found to stimulate somatostatin expression in a dosage-dependent fashion. The somatostatin-stimulating activity induced SOM-IR in more than 90% of CG neurons, as well as in retrogradely labeled ciliary neurons, which would not normally express SOM-IR. Thus, the expression of somatostatin in cultured CG neurons is regulated by a macromolecule produced by cells in the choroid layer, a target normally innervated in vivo by CG neurons expressing somatostatin.

Actins↗

Vascular effects of acetazolamide on the choroid plexus.

Decreases in production of cerebrospinal fluid (CSF) after administration of acetazolamide have been attributed in part to constriction of blood vessels of the choroid plexus. The first goal of the present study was to examine effects of acetazolamide on blood flow to the choroid plexus. We measured blood flow (microspheres) and the production of CSF (ventriculo-cisternal perfusion) in anesthetized rabbits. Under control conditions, blood flow to the choroid plexus was 466 +/- 34 (mean +/- S.E.) ml min-1 100 g-1 and CSF production was 9.4 +/- 0.9 microliters min-1. Acetazolamide (25 mg kg-1 i.v.) decreased production of CSF by 55 +/- 5% despite a 2-fold increase in blood flow to the choroid plexus. The second goal of this study was to examine the role of hypercapnia, which occurs after administration of acetazolamide, in producing increases in blood flow. In animals in which hypercapnia was prevented by increases in ventilation, acetazolamide produced a similar increase in blood flow to the choroid plexus. We conclude that acetazolamide decreases the production of CSF but, in contrast to predictions based on studies in vitro, acetazolamide produces a marked increase in blood flow to the choroid plexus. Thus, changes in blood flow to the choroid plexus and production of CSF are uncoupled after administration of acetazolamide.

Acetazolamide↗

[Localization of occult choroid neovascularizations].

The purpose of this study was to investigate the localization of the choroidal neovascular membrane of 17 eyes in the disciform stage of age-related macular degeneration. Indocyanine green videoangiography could reliably define the presence of the choroidal neovascular membrane despite the failure of fluorescein angiography. Where the indocyanine green videoangiographic and fluorescein angiographic findings were compared we found that (1) in 11 out of 17 eyes, the choroidal neovascular membrane in indocyanine green videoangiography was observed in the subretina or the subretinal pigment epithelium, although this was found to be overlaid with hemorrhage or serous fluid in fluorescein angiography; (2) in 6 eyes, the choroidal neovascular membrane was demonstrated in the area without retinal pigment epithelial detachment. In fact, even though the choroidal neovascular membrane was only visible as a "window defect" due to minimal retinal pigment epithelial damage that in fluorescein angiography, in indocyanine green videoangiography the membrane was seen as early abnormal choroidal vessels and late leakage. This implies that a disciform lesion may be caused by the choroidal neovascular membrane, even when this is only minimally invading the subretinal pigment epithelial space.

Aged↗

Alkaline phosphatase activity of the IVth ventricular choroidal epithelium of rats during embryonic and neonatal development.

The cytochemical localization of alkaline phosphatase (AlPase) activity in the developing IVth ventricular choroidal epithelium was investigated in embryonic and neonatal rats. During the initial development of the choroidal primodium the flattened and/or cuboidal epithelial cells of the ventricular roof were changed to columnar cells with well-developed microvilli and apical tight junctions. When compared to AlPase activity on the lateral plasma membranes of the surrounding ependymal cells, these columnar cells of the choroidal primodium revealed activity on the lateral and luminal plasma membranes, but no activity was found on the basal surface of these cells. On the other hand, the epithelial cells in the neonatal choroid plexus showed a continuous morphological alteration from columnar cells with short microvilli to mature cuboidal cells with numerous long microvilli. AlPase activity in immature columnar cells was observed on all plasma membranes, except for the apical junctional area of the lateral surface. With maturing of the choroidal epithelial cells, the activity appeared to be eliminated from the lateral and luminal plasma membranes of the cuboidal cells, and mature choroidal epithelial cells showed activity on the basal surface only. These findings suggest that AlPase may play an important role in the membrane activity of epithelial cells differentiating between the primitive epithelial cells of the ventricular roof and the mature choroidal epithelial cells.

Alkaline Phosphatase↗

Magnetic resonance imaging and computed tomography of choroidal detachment.

The magnetic resonance imaging (MRI) and computed tomography (CT) findings in 9 patients with hemorrhagic choroidal detachment, serous choroidal detachment and/or ocular hypotony, choroidal effusion and 6 patients with exudative retinal detachment are described. Subacute hemorrhagic choroidal detachment appeared as moderately hyperintense image in T1 weighted MR scans and as hypointense in T2 weighted scans. Chronic hemorrhagic choroidal detachment was seen as hyperintense image in T1 and T2 weighted scans. Serous choroidal detachment and choroidal effusion appeared as moderately hyperintense image in T1 and T2 weighted scans. The exudative retinal detachment characteristically appeared on MR scans as a dependent hyperintense object in T1 and T2 weighted scans.

Choroid Diseases↗

Thyroxine transport in choroid plexus.

The role of the choroid plexus in thyroid hormone transport between body and brain, suggested by strong synthesis and secretion of transthyretin in this tissue, was investigated in in vitro and in vivo systems. Rat choroid plexus pieces incubated in vitro were found to accumulate thyroid hormones from surrounding medium in a non-saturable process. At equilibrium, the ratio of thyroid hormone concentration in choroid plexus pieces to that in medium decreased upon increasing the concentration of transthyretin in the medium. Fluorescence quenching of fluorophores located at different depths in liposome membranes showed maximal hormone accumulation in the middle of the phospholipid bilayer. Partition coefficients of thyroxine and triiodothyronine between lipid and aqueous phase were about 20,000. After intravenous injection of 125I-labeled thyroid hormones, choroid plexus and parts of the brain steadily accumulated 125I-thyroxine, but not [125I]triiodothyronine, for many hours. The accumulation of 125I-thyroxine in choroid plexus preceded that in brain. The amount of 125I-thyroxine in non-brain tissues and the [125I]triiodothyronine content of all tissues decreased steadily beginning immediately after injection. A model is proposed for thyroxine transport from the bloodstream into cerebrospinal fluid based on partitioning of thyroxine between choroid plexus and surrounding fluids and binding of thyroxine to transthyretin newly synthesized and secreted by choroid plexus.

Animals↗

The natural course of active choroidal lesions in the presumed ocular histoplasmosis syndrome.

Eighty-two patients and 106 eyes with the POHS have been followed for one year or longer. Untreated active choroidal lesions were divided into groupings based on the distance from the center of the CFZ and the reltionship to the border of the CFZ. Twenty-three percent of untreated active choroidal lesions that were located inside the CFZ achieved 20/20 to 20/40 vision. Sixty-three percent of untreated active choroidal lesions that were located outside of the CFZ achieved a vision of 20/20 to 20/40. The active choroidal lesions with the best visual prognosis were 0.25 to 0.5 disc diamterers, demonstrated no growth, and had little or no associated choroidal bleeding. Activation of choroidal lesions in the fellow eye at the site of preexisting atrophic scars was documented in 21% of the eyes. One fellow eye developed a de novo active choroidal lesion. Eighteen percent of the cases had structurally congested nerve heads characterized by slight elevation of the disc and no physiologic depression; 3% of the eyes had drusen of the optic nerve. A relationship may exist between peripapillary scarring in the POHS and these nerve head changes.

Adolescent↗

Active transport of riboflavin by the isolated choroid plexus in vitro.

In vitro, the transport of [14C]riboflavin into and from the isolated choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, was studied. With concentrations of [14C]riboflavin of 0.7 microM (or greater) in the incubation medium, the choroid plexus accumulated [14C]riboflavin against a large concentration gradient by a process that did not depend on binding or intracellular metabolism of the [14C]riboflavin. The [14C]riboflavin accumulation process in isolated choroid plexus could be described by Michaelis-Menten transport kinetics (kt = 78 microM and Ymax = 1.65 mmol kg-1 (15 min)-1) and was inhibited by other flavins and probenecid but not by ribose, weak bases, or other B vitamins. The accumulation process was markedly depressed by iodoacetate and low temperatures. With a concentration of 0.08 microM [14C]riboflavin in the incubation medium, 28% of the [14C]riboflavin within the choroid plexus was converted to [14C]FAD or [14C]FMN intracellularly. Unlike the active transport of [14C]riboflavin into choroid plexus, accumulated [14C]riboflavin departed choroid plexus by a process independent of intracellular concentration or temperature. The efflux of [14C]riboflavin from choroid plexus could be described by first oder kinetics with a rate constant of -0.08 min-1.

Animals↗