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PubMed1998

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase II remained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity.

Adaptation, Physiological↗
PubMed1998

Treatment of villous hypertrophy of the choroid plexus by endoscopic contact coagulation.

Villous hypertrophy of the choroid plexus (VHCP) is a condition characterized by overproduction of cerebrospinal fluid by bilaterally symmetric and enlarged, yet histologically normal, choroid plexi. Medical and surgical therapy have been met with variable success. Traditional shunting procedures often result in failure to correct the underlying problem as well as failure to absorb the large volume of fluid produced. Craniotomy for open surgical resection of the choroid is associated with considerable morbidity. The authors describe a technique of endoscopic contact coagulation as an effective and safe treatment of VHCP. A 14-month-old hydrocephalic girl with VHCP who failed ventriculoperitoneal shunting as the sole treatment of her hydrocephalus presented with increasing ascites. She was successfully treated with ventriculoperitoneal shunting and endoscopic Bugby wire-directed monopolar contact coagulation of the hyperplastic choroid plexus. Postoperatively her head circumference and cognitive development is normal for her age, and her ascites has resolved. Endoscopic contact coagulation of the hyperplastic choroid plexus is a minimally invasive surgical method which treats the cause of the CSF production while avoiding the operative complications of open choroid plexus resection.

Choroid Plexus↗
PubMed1998

Secretion of cytokines by human choroidal melanoma cells and skin melanoma cell lines in vitro.

The selective secretion of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), basic fibroblast growth factor (b-FGF) and transforming growth factor beta 1 (TGF beta-1) in tissue culture of choroidal melanomas and two established skin melanoma cell lines was investigated with ELISA analysis. Values of choroidal melanoma cells were compared with the melanoma cell lines and human fibroblasts as a physiological control. High secretion of IL-6 was detectable in choroidal melanoma cultures but not in the cell lines. IL-8 secretion was found in all melanoma cultures. However, IL-10 was only secreted by one skin melanoma cell line and in choroidal melanoma cell cultures. B-FGF secretion by choroidal melanomas was higher than by cell lines. No differences were seen in the amounts of TGF beta-1 produced by melanoma cells. Human fibroblasts produce higher amounts of IL-6 and IL-8 but lower of b-FGF in vitro in contrast to the melanoma cells. The secretion of cytokines by choroidal melanoma cells suggests an important role of these soluble factors in the interaction of tumour and healthy tissue.

Choroid Neoplasms↗
PubMed2006

Chronic hypernatremia increases the expression of vasopressin and voltage-gated Na channels in the rat choroid plexus.

The choroid plexus (CP) epithelium is one of the extrahypothalamic sources of arginine vasopressin (AVP). However, it is unclear whether the regulation of choroidal AVP synthesis in response to pathophysiological stimuli, such as hyperosmotic stress, is similar to that observed in the hypothalamus. In the present study, rats chronically implanted with cisterna magna cannulas, enabling the collection of cerebrospinal fluid (CSF) in freely moving animals, were subjected to salt loading. CSF osmolality increased from the baseline normonatremic levels ranging between 292 +/- 0.5 and 295 +/- 2 to 309 +/- 4 mosm/kg H(2)O at 2 days of hypernatremia. This elevated CSF osmolality was maintained at a relatively stable level until the end of a 10-day observation period. Changes in choroidal and hypothalamic AVP expression in response to hyperosmotic stress were assessed by semiquantitative reverse-transcriptase polymerase chain reaction. An increase in hypothalamic AVP expression was accompanied by augmented AVP synthesis in the CP. Compared to normonatremia, choroidal levels of AVP mRNA increased 5- and 10-fold at 2 and 5 days of salt loading, respectively. Salt loading also resulted in increased hypothalamic expression of the alpha-II, beta(1), and beta(2) subunits of voltage-gated Na(+) channels. Similarly, the choroidal mRNA levels for the alpha-II and beta(1) subunits increased approximately 2-fold after 5 days of salt loading; however, no changes in the beta(2) subunit expression were found in the CPs of hypernatremic rats. These experiments support the hypothesis that the regulation of choroidal AVP synthesis is similar to that observed in the hypothalamus. It is also suggested that the increased expression of voltage-gated Na(+) channels found in the hypothalamus and CP after salt loading may play a role in the adaptation of AVP-producing cells to chronic hypernatremia.

Animals↗
PubMed1981

Percutaneous choroid plexus coagulation in hydranencephaly.

Percutaneous intracranial endoscopy, performed on 3 infants with hydranencephaly and signs of intracranial hypertension, showed normal choroid plexus and choroid arteries in 2 patients. Transendoscopic coagulation of the arteries and plexus alleviated intracranial hypertension postoperatively. Minimal choroid plexus and no choroid arteries were present in the 3rd patient and coagulation did not alter the clinical course. Computerized tomography scans of the infants with normal choroid plexus demonstrated cerebral tissue in the region of the caudate nucleus; the child with minimal choroid plexus had tissue only in the region of the posterior thalamus.

Anencephaly↗
PubMed1995

Massive infarcts involving the territory of the anterior choroidal artery and cardioembolism.

BACKGROUND AND PURPOSE: At neuropathological examination, the territory of the anterior choroidal artery is frequently found to be involved in massive infarcts of the internal carotid artery territory. The aim of our study was to analyze the clinical spectrum, the course, and the mechanism of these massive infarcts compared with the rare infarcts involving only the anterior choroidal artery territory. METHODS: Retrospective clinical examination and pathological study were performed in 35 patients with cerebral infarcts affecting at least the territory of the anterior choroidal artery. RESULTS: In no patient had the involvement of the anterior choroidal territory infarcts been recognized clinically, nor had the triad of clinical signs (hemiplegia, hemianesthesia, and hemianopsia) classically seen in infarcts restricted to this territory been found alone. Impairment of consciousness, cognitive disorders, or oculomotor palsies had been found in addition to one or more signs of the triad. This was probably related to the involvement of other territories (94%), especially the middle cerebral artery territory (68%) and the posterior cerebral artery territory (20%). The concomitant involvement of several territories was due most frequently to an occlusion of the internal carotid artery, which was found at autopsy in 74% of the patients. These occlusions were often associated with cardioembolism (54%). In contrast, artery-to-artery embolism (17%) and small-artery disease (6%) were seldom found. Only two cases of infarcts restricted to the anterior choroidal artery territory were observed. CONCLUSIONS: The involvement of the territory of the anterior choroidal artery in massive infarcts was due mainly to a cardioembolic occlusion of the internal carotid artery.

Aged↗
PubMed2003

Choroidal vascular reaction to hand-grip stress in subjects with vasospasm and its relevance in glaucoma.

PURPOSE: To assess the impact of vascular dysregulation on choroidal blood flow response to the hand-grip test and the relevance of this response to glaucoma. METHODS: Eighty healthy volunteers underwent a hand-grip test while choroidal blood flow was measured by means of laser Doppler flowmetry. Blood pressure, heart rate, and intraocular pressure (IOP) were monitored. Choroidal blood flow changes were compared between subjects with a positive history of cold hands and control subjects by means of analysis of variance. The relationship of the vascular response to the level of IOP at which progressive damage occurred was analyzed in 21 patients with primary open-angle glaucoma who had progressive damage despite normal or normalized IOP. RESULTS: Blood pressure and heart rate increased and IOP decreased in response to a hand-grip test. Healthy subjects with a positive history of cold hands (n = 36) demonstrated a decrease in choroidal blood flow during the hand-grip test (mean +/- SD: 13.5 +/- 5.8, 12.2 +/- 6.8, and 13.4 +/- 6.9 AU, at baseline, during the test, and 3 minutes after release, respectively), whereas control subjects (n = 44) demonstrated an inverse (12.5 +/- 8.3, 13.7 +/- 9.4, and 11.9 +/- 7.1 AU, respectively) response pattern (P = 0.039). Glaucoma patients with a decrease of at least 10% in choroidal blood flow during the hand-grip test had lower IOP (14.67 +/- 3.83 and 13.50 +/- 2.59 mm Hg in the right and the left eyes, respectively) compared (P = 0.032) with those without such a decrease (16.54 +/- 3.85 and 16.92 +/- 2.95 mm Hg in the right and the left eyes, respectively). CONCLUSIONS: A hand-grip test elicits a different blood flow response in subjects with vasospasm compared with control subjects. Damage by glaucoma in patients with a decrease in choroidal blood flow during a hand-grip test may progress at a relatively lower IOP.

Adult↗
PubMed2003

Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans.

PURPOSE: There is evidence from a variety of animal studies that the adenosine system plays a role in the control of intraocular pressure (IOP) and ocular blood flow. However, human data on the effect of adenosine on IOP and choroidal and optic nerve blood flow are not available. METHODS: The effect of stepwise increases in doses of adenosine (10, 20, and 40 micro g/kg per minute, 30 minutes per infusion step) on optic nerve head blood flow, choroidal blood flow, and IOP was determined in a placebo-controlled double-masked clinical trial in 12 healthy male volunteers. Blood flow in the optic nerve head and choroid was measured with laser Doppler flowmetry. In addition, fundus pulsation amplitude in the macula (FPAM) and the optic nerve head (FPAO) were assessed with laser interferometry. RESULTS: Adenosine induced a small but significant decrease in IOP (at 40 microg/kg per minute: 12% +/- 13%), which was significant versus placebo (P = 0.046). In addition, adenosine induced a significant increase in choroidal blood flow (P < 0.001) and optic nerve head blood flow (P = 0.037), and FPAM (P = 0.0014) and tended to increase FPAO (P = 0.057). At the highest administered dose, the effect on choroidal hemodynamic parameters between 14% and 17%, whereas the effect on optic nerve hemodynamic parameters was between 3% and 11%. CONCLUSIONS: These data are consistent with adenosine inducing choroidal and optic nerve head vasodilatation and reducing IOP in healthy humans. Considering the neuroprotective properties of adenosine described in previous animal experiments the adenosine system is an attractive target system for therapeutic approaches in glaucoma.

Adenosine↗
PubMedDate not supplied

Simultaneous bilateral primary choroidal melanoma.

A case of bilateral primary choroidal melanoma is described. To our knowledge, this is the first reported case in Spain. On admission of a 70-year-old man for a choroidal melanoma in the right eye, an asymptomatic tumor was detected in the periphery of his left eye. A-scan ultrasonography, fluorescein angiography and diascleral transillumination supported the diagnosis of choroidal melanoma in both eyes. The right eye was enucleated. Histology confirmed a choroidal melanoma of the mixed type. The left eye was treated with laser photo-coagulation and an episcleral plaque of ruthenium-106. Careful systemic evaluation produced no evidence of a primary tumor or metastatic disease elsewhere in the body. Because of the impossibility, in most cases, of obtaining histological confirmation in both eyes, and the tendency of choroidal melanomas to metastatize late, we suggest that the criteria of independent origin (two separate cell types and tumors separated in time) are not necessary in cases of presumed bilateral choroidal melanoma.

Aged↗
PubMed1994

Sustained regression of a primary choroidal melanoma under the influence of a therapeutic melanoma vaccine.

PURPOSE: To determine whether active specific immunotherapy with lysates of cutaneous melanoma cells, administered with immunologic adjuvant DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT), is effective in shrinking a primary choroidal melanoma, in an elderly patient already blind in the nontumorous eye. An 81-year-old man was referred with a primary choroidal melanoma of the left eye, with virtual blindness of the right eye due to macular degeneration. He was begun on active specific immunotherapy with an experimental melanoma vaccine (melanoma theraccine) and DETOX on weeks 1, 2, 3, 4, and 6, respected after a hiatus of 2 weeks. After a response was noted, monthly injections were given. RESULTS: The patient had a significant shrinkage of his choroidal melanoma from a height of 4.2 mm to 2.4 mm within 2 months. This was sustained by continual treatment for 21 months until September 1991. After the patient failed to return for 9 months while recuperating from a stroke, the lesion regrew to a height of 3.7 mm and developed an additional lobe. On resumption of monthly treatments, the lesion shrank to 3.4 mm within 3 months, lost the additional lobe, and has since remained stable. No metastases have been found over a period of nearly 4 years on quarterly computed tomographic (CT) scanning of the chest and abdomen, and magnetic resonance imaging of the head. CONCLUSION: Active specific immunotherapy with cutaneous melanoma lysates has caused a clinically useful protracted regression of a primary choroidal melanoma in an elderly patient in whom surgery and radiation therapy were contraindicated. This may represent the first case of a primary choroidal melanoma, and perhaps the only primary tumor, successfully treated with systemic immunotherapy alone. A formal trial of active specific immunotherapy for primary choroidal melanoma in selected patients may be warranted.

Adjuvants, Immunologic↗
PubMed1984

Retinal and choroidal blood flows in hypoxic and hypercarbic newborn lambs.

We studied the effect of changes in the arterial tensions of oxygen and carbon dioxide on blood flow to the retinal (RBF) and choroidal ( ChBF ) capillary beds in 20 lambs. One to three days after placement of catheters in the left ventricle, abdominal aorta, and brachiocephalic artery, different gas mixtures were delivered to a bag enclosing the lamb's head. One group of lambs was studied at normal and low oxygen tensions while normocarbic , and another group was studied at normal and high carbon dioxide tensions while normoxic. RBF and ChBF were measured using the radioactive microsphere technique. RBF increased as PaO2 and, thus, arterial oxygen content [( O2]a) fell; in contrast, ChBF was not related to [O2]a. Oxygen delivery to the capillary bed of the retinal artery (i.e., RBF X [O2]a) was independent of arterial oxygen content because the change in [O2]a was balanced by a reciprocal change in RBF. Oxygen delivery to the choroidal capillary bed, however, rose with [O2]a because there was no reciprocal decrease in ChBF . Both RBF and ChBF increase as arterial carbon dioxide tension rose. Although an increase in arterial carbon dioxide tension produced an increase in RBF with no change in [O2]a, oxygen delivery to the retinal capillaries rose. Similarly, oxygen delivery to the capillaries of the choroid rose with carbon dioxide tension. Oxygenation of retinal tissue, which depends on oxygen diffusion from both the retinal and choroidal capillary beds, may change with variations in arterial oxygen content (increase in oxygen delivered to the choroidal capillary bed) or arterial carbon dioxide tension (increase in oxygen delivered to both the retinal and choroidal capillary beds).

Animals↗
PubMed1992

Prolactin enhancement of its own uptake at the choroid plexus.

The choroid plexus contains PRL receptors that function in part to transport PRL from the blood into the cerebrospinal fluid (CSF). The blood PRL concentration of female rats was altered by 1) three daily injections of haloperidol (chronic hyperprolactinemia) with or without bromocriptine administration 4 h before death, 2) bromocriptine alone for 4 h (acute hypoprolactinemia), and 3) a single vascular injection of ovine PRL (acute hyperprolactinemia). Changes in the uptake of PRL by the choroid plexus was assessed by quantitative in vivo autoradiography after the injection of radiolabeled PRL. Correlation of changes in PRL uptake at the choroid plexus with changes in PRL transport from blood to CSF was evaluated by subjecting CSF samples to sodium dodecyl sulfate-polyacrylamide gel electrophoresis after vascular injection of radiolabeled PRL. Autoradiography revealed that both chronic and acute hyperprolactinemia resulted in a significant increase in the uptake of radiolabeled PRL by the choroid plexus compared to that in untreated control animals. In contrast, bromocriptine had no effect on PRL uptake at the choroid plexus relative to that in control (untreated) animals. Chronic hyperprolactinemia, but not acute hyperprolactinemia, resulted in a significant increase in the transport of radiolabeled PRL from the blood to the CSF compared to that in untreated controls. The results are consistent with the up-regulation of PRL receptors in the choroid plexus by circulating PRL and the consequent augmentation of transport of PRL from blood to CSF.

Animals↗
PubMed1993

Thyroxine transport to the brain: role of protein synthesis by the choroid plexus.

A cell culture model for the blood-cerebrospinal fluid barrier in choroid plexus was developed. The relationship between synthesis and secretion of transthyretin across a layer of epithelial cells derived from rat choroid plexus and the transport of T4 was analyzed in a two-chamber system. Choroid plexus cells were dispersed and placed on a porous filter suspended in cell culture medium. A monolayer of polarized epithelial cells developed after 5 days in culture, separating fluid in the upper (apical) chamber from fluid in the lower (basal) chamber. Electrical resistance across the cell layer was 100 Ohm/cm2. Transthyretin was synthesized and secreted by these cells. Over 32 h, transthyretin accumulated in the fluid in the apical chamber to twice the concentration in the basal chamber. [125I]T4 added to the basal chamber permeated to the apical fluid and accumulated in the apical chamber to twice the concentration in the basal fluid. Upon inhibition of protein synthesis, T4 equilibrated to a similar concentration in the two chambers. Thus, the accumulation of T4 in the apical chamber required continuing protein synthesis. Competitive inhibition of T4 binding to transthyretin by EMD 21388 also prevented the accumulation of T4 to a higher concentration in the upper than in the lower chamber. These data suggest that T4 partitions through the choroid plexus and that transthyretin synthesis and secretion by the choroid plexus determines the concentration of T4 in the apical fluid. A model is proposed for the involvement of transthyretin secreted by the choroid plexus, in the in vivo distribution of T4 in the brain.

Animals↗
PubMed1986

Comparative uptake of cimetidine by rat choroid plexus between the lateral and the 4th ventricles.

It is suggested that cimetidine interacts with the transport system for organic anions and oligopeptides in the rat lateral ventricular choroid plexus. In this study, we studied the transport system of cimetidine in the rat 4th ventricular choroid plexus to examine the heterogeneity in the ability to accumulate cimetidine between the lateral and the 4th ventricular choroid plexus. The similar time course of the accumulation of cimetidine was obtained between both choroid plexuses. Furthermore, the accumulation of cimetidine by the choroid plexus from the 4th ventricle was inhibited by unlabelled cimetidine (1 mM) and benzylpenicillin (1 mM) but not by tetraethylammonium (1 mM). These findings suggested that the rat choroid plexuses from the lateral and the 4th ventricle have similar characteristics in transporting cimetidine.

Animals↗
PubMed1998

A quantitative assay for angiogenesis of cultured choroidal tissues in streptozotocin-diabetic Wistar and spontaneously diabetic GK rats.

Angiogenesis of cultured choroids was quantitatively assayed in spontaneously diabetic GK and a bolus-treated streptozotocin (STZ)-diabetic Wistar rats. The number and total length of microvessels budded from cultured choroidal explants were measured to use as angiogenic indices. Both indices in 10-week-old Wistar rats were increased in parallel by 5% fetal bovine serum (FBS) from days 2 to 7 in culture. These indices in STZ-rats (10 weeks of age) were increased by 5% FBS to a greater extent than those in age-matched normal rats. These enhanced actions of FBS were concentration-dependent. The explants of 16-week-old GK rats also increased these indices to a greater extent than those of age-matched Wistar rats. Aging to 18 weeks of age also increased choroidal angiogenesis in the normal rats. In conclusion, the assay model of choroidal angiogenesis was established by determining the number and length of microvessels in cultured choroidal explants. The diabetic states of STZ-Wistar and GK rats enhanced FBS-induced choroidal angiogenesis. This assay model is useful for determining angiogenic activity of growth factors and effective drugs in diabetic choroidopathy and retinopathy.

Aging↗
PubMed2002

An in vitro model of the back of the eye for studying retinal pigment epithelial-choroidal endothelial interactions.

At the back of the eye, the outermost cell layer of the retina, the pigmented epithelium, lies against a basement membrane that is adjacent to the choroidal vessels that supply the outer sensory retina. During pathogenesis, these interfaces become damaged, and the homeostatic balance between the retinal pigment epithelium (RPE) and the choroidal vessels becomes disrupted, leading to choroidal neovascularization and blindness. To study the cell interactions at the back of the eye, we have used a coculture system in which a stable RPE monolayer has been cultured on a transwell insert and placed over a collagen gel sandwich into which choroidal endothelial cells (CECs) have been seeded. RPE cells have been stimulated by an inflammatory cytokine, interleukin-1 (IL-1beta), and the ability of the underlying choroidal endothelium to form vascular tubes has been tested. IL-1beta stimulation of the RPE insert increased the number of tubes formed by CECs in the gel as early as 3 d. By 7 d, tubes began to regress. Both IL-8 and monocyte chemotactic protein-1 (MCP-1) were found to be secreted in greater amounts in stimulated RPE. Because MCP-1 is also a chemokine for monocytes, which in turn secrete angiogenic factors, monocytes were added to the upper surface of the choroidal gel sandwich and then incubated with the stimulated RPE insert as above. By day 7, more tubes formed and there was no regression over the experimental time period. The versatility of this model has been illustrated in that both RPE and CECs can be cultured in a more natural construct and their molecular interactions tested by physiologically altering one cell type and not the other.

Animals↗
PubMed2005

NPY and TH innervation in human choroidal whole-mounts.

To determine the distribution of NPY and TH human choroidal innervation, choroidal whole-mounts were processed for indirect immunofluorescence. An antibody to a component of the neuronal cytoskeleton, neurofilament 200 kDa (NF-200) was used to identify neurons and axons. A double immunostaining was performed, antibodies against NF-200 being combined with antibodies against neuropeptide Y (NPY) and tyroxine hydroxylase (TH). Fibers containing both NPY and TH were distributed in three plexuses, one in the suprachoroid large-sized vessel layer, and two in the medium-sized vessel layer. Intrinsic choroidal neurons (ICNs) containing NPY and TH were observed in the suprachoroid. The TH(+) ICNs were located in the medium-sized vessel layer. Overall, NPY(+) and TH(+) ICNs were more frequent in the central temporal area, both in isolation and forming microganglia. We also detected small spindle elements intensely immunoreactive to TH(+) and distributed mainly in the suprachoroid from the equator to the periphery. In conclusion, the human choroid contains abundant NPY and TH nerve fibers related to chroroidal vascular structures; it further possesses NPY(+) and TH(+) ICNs which contribute to the choroidal self-regulation persisting after sympathetic denervation. Additionally, these ICNs may at least partially explain why the choroidal blood flow does not respond to the factors that influence systemic vascular control. The preferential location of these cells in the submacular area suggests that dysfunction or degeneration of these cells may be a factor in vascular pathologies found in ocular disease, such as diabetic macular edema or age-related macular degeneration.

Adult↗
PubMedDate not supplied

Comparisons of the structural and chemical properties of melanosomes isolated from retinal pigment epithelium, iris and choroid of newborn and mature bovine eyes.

Melanosomes were isolated from the retinal pigment epithelium (RPE), iris and choroid of mature (age >2 years) and newborn (age <1 week) bovine eyes. Scanning electron microscopy was utilized to analyze the morphology of the melanosomes, which were found to vary among different tissues and different ages. While the total content of amino acids differs slightly (ranging from 9% to 15% by mass), the distributions of the amino acids are similar. The pheomelanin content is low in the choroid and the RPE (0.1-0.5%), and moderate in the iris (<2%); therefore, the major melanin component of bovine eye melanosomes is eumelanin, independent of the shape of the melanosomes. The yields of pyrrole-2,3,5-tricarboxylic acid from melanosomes decrease in the following order: choroid > iris > RPE, and exhibit decreasing yields with age. 13C solid-state nuclear magnetic resonance (NMR) spectroscopic analysis of iris and choroid melanosomes indicates the same trends. These observations suggest that the 5,6-dihydroxyindole-2-carboxylic acid contents decrease in the following order: choroid > iris > RPE, and decrease with age. Moreover, the 13C solid-state NMR spectra show (1) for the same age samples, the CH:Cq ratio for choroid is larger than that for iris melanosomes; and (2) an increase in the concentration of carbonyl groups with age within each type of melanosome.

Adult↗