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PubMed1985

Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental.

Choroid plexus contains an active transport (influx) and a facilitated diffusion (efflux) system for nucleosides. The ability of diazepam and thiopental to inhibit active transport or facilitated diffusion of thymidine in choroid plexus was measured in vitro under various conditions. When isolated rabbit choroid plexuses were incubated in artificial cerebrospinal fluid containing 1 microM [3H] thymidine for 10 min at 37 degrees C under 95% O2-5% CO2, diazepam (10 microM) and thiopental (500 microM) doubled the tissue-to-medium ratios of [3H] thymidine from 8 to 15 to 16. These results were not due to metabolism or intracellular binding but rather to inhibition of [3H] thymidine efflux from choroid plexus. Diazepam, unlike thiopental, inhibited [3H] thymidine efflux in a concentration-dependent manner. When isolated choroid plexuses were incubated in artificial cerebrospinal fluid containing low concentrations of [3H] thymidine (6 nM) to allow intracellular conversion of [3H] thymidine into [3H] thymidine phosphates and [3H] DNA, both diazepam (10 microM) and thiopental (500 microM) altered [3H] thymidine accumulation and metabolism consistent with inhibition of facilitated diffusion but not active transport of thymidine. These studies provide evidence that, at toxic but not therapeutic concentrations, diazepam and thiopental alter facilitated nucleoside transport in the choroid plexus.

Animals↗
PubMed1985

125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells.

125I-Lysergic acid diethylamide (125I-LSD) binds with high affinity to serotonergic sites on rat choroid plexus. These sites were localized to choroid plexus epithelial cells by use of a novel high resolution stripping film technique for light microscopic autoradiography. In membrane preparations from rat choroid plexus, the serotonergic site density was 3100 fmol/mg of protein, which is 10-fold higher than the density of any other serotonergic site in brain homogenates. The choroid plexus site exhibits a novel pharmacology that does not match the properties of 5-hydroxytryptamine-1a (5-HT1a), 5-HT1b, or 5-HT2 serotonergic sites. 125I-LSD binding to the choroid plexus site is potently inhibited by mianserin, serotonin, and (+)-LSD. Other serotonergic, dopaminergic, and adrenergic agonists and antagonists exhibit moderate to weak affinities for this site. The rat choroid plexus 125I-LSD binding site appears to represent a new type of serotonergic site which is located on non-neuronal cells in this tissue.

Animals↗
PubMed1979

A morphological study of the development of the mouse choroid plexus.

Development of the mouse choroid plexus was studied by semithin light microscopy, transmission electron microscopy and scanning electron microscopy. The choroid plexus is first observed as a bilateral ridge at 11 days postconception. The major morphological development appears to occur between 11 and 14 days postconception. By 14 days both dark and light choroid plexus epithelial cells are present. The percentage of dark cells appears constant from 14 days postconception up to 3 months postnatum. Metachromatically staining glycogen masses are present in the choroidal epithelium from 13 days postconception until 5 days postnatum, after which time glcogen granules are sparsely scattered throughout the cytoplasm. A few fine microvilli are present at 11 days postconception and these increase in number and become much more bulbous by 13 days. In contrast to the light choroid plexus epithelial cells, the dark cells have fine narrow microvilli. The possible significance of the two types of choroid plexus cells is discussed.

Aging↗
PubMedDate not supplied

Choroidal osteoma.

Choroidal osteomas are benign, juxtapapillary, choroidal tumors that mandate no treatment. They occur predominantly in young (median age, 20 years) females (90%). While ophthalmoscopy and fluorescein angiography reveal suggestive ophthalmic findings, echography, plain radiography, and especially computed tomography (CT) are important in establishing the correct diagnosis. These lesions may be clinically confused with various dystrophic lesions, atypical or amelanotic malignant choroidal melanoma, metastatic carcinoma, leukemic or lymphomatous infiltrates, choroidal hemangioma, choroidal scars of the macula, and organized subretinal hemorrhage. The exclusion of the differential consideration of malignant melanoma is most important since radiation and enucleation are therapeutic possibilities. Review of the literature shows that all nine reported cases with CT scans had clearly demonstrable calcific densities in the posterior pole of the affected eye. Four other cases are reported here with a summary of the typical clinical, radiologic, and pathologic findings. The role of CT in the evaluation of choroidal osteoma and the distinctiveness of the CT findings are stressed.

Adolescent↗
PubMed1981

Ultrastructure of the choroid plexus and its development in the mouse.

The morphogenesis of the choroid plexus of the lateral ventricle of the mouse was studied from the 8th to the 13th post conception day (PCD) in semi- and ultra-thin sections. The choroid plexus appears on PCD 11 with the formation of a horizontal crest in the roof of the interventricular foramen. However, degenerative processes play an important role in the morpho- and histogenetic development of the choroid plexus from PCD 8. During the degenerative period the epithelial cells differentiate and stratify to form the choroid plaque. From PCD 11 the developing choroid plexus expands into the ventricular cavity taking with it mesenchyme and vessels. Ultrastructurally, the epithelial cells differentiate into cells which are more cylindrical and whose nuclei become more elongated. The cytoplasm exhibits numerous prolongations into the ventricular cavity. The golgi complexes, the endoplasmatic reticulum, the ribosomes and polyribosomes are found concentrated in the apical portions of these cells. The apical prolongations of three or more neighbouring cells form "lakes". Junctional complexes between the apical ends of the epithelial cells radiate out from the lakes in which there are microvilli. Macrophages, or "epiplexus cells", frequently give rise to thin cellular processes which encompass protrusions of the epithelial cells. These epiplexus cells contain many vacuoles and phagosomes; numerous mitochondria are localized adjacent to those epiplexus plasma membranes encompassing protrusions. It is proposed that the epithelial cells of the choroid plexus contribute to the formation of the embryonic encephalic liquid.

Animals↗
PubMed1995

[Occurrence of choroidal neovascularization following photocoagulation treatment for central serous retinopathy].

Occurrence of choroidal neovascularization following laser photocoagulation treatment for central serous retinopathy (CSR) has been reported. We reviewed all the cases of photocoagulation treatment for CSR in our clinic during the past 25 years (1968-1993). Among 1,824 CSR-affected eyes which were treated, choroidal neovascularization occurred in 19 at the site of photocoagulation. In a careful reevaluation of pretreatment fluorescein angiograms, small choroidal neovascularizations were detected in 5 eyes, in which cases the diagnosis of CSR was incorrect. In 3 eyes, choroidal neovascularization was suspected and might have been masked. In the remaining 11 eyes, choroidal neovascularization was not seen. Our survey indicates that, in central serous retinopathy, when the age of the patient is over 50 years, and leakage is weak and parafoveal, choroidal neovascularization may be masked. Laser photocoagulation for these eyes should be conservative with careful, long-term observation.

Adult↗
PubMed1995

[Expression of fibroblast growth factor receptor 1 in experimental choroidal neovascularization with in situ hybridization].

Fibroblast growth factor (FGF) is an important factor for neovascularization in vivo. In order to clarify the role of FGF in experimentally produced choroidal neovascularization, we demonstrated mRNA for FGF receptor 1 in situ hybridization. Krypton laser photocoagulation was applied to the posterior retina of colored rats to produce choroidal neovascularization experimentally. These eyes were removed at several different intervals after photocoagulation. Chorioretinal section were used for in situ hybridization. FGF receptor 1 cDNA fragment was used to make antisense and sense probes for in situ hybridization. In normal chorioretinal tissue, staining indicating the existence of FGF receptor 1 mRNA was seen in the ganglion cell layer and inner nuclear layer. After the photocoagulation, the staining was seen in the retinal pigment epithelial cells, melanocytes in the choroid, and choroidal blood vessel wall in the photocoagulated lesions. FGF receptor 1 mRNA was expressed through the development of choroidal neovascularization, and it appears that FGF is necessary for development of choroidal neovascularization. Previous workers showed that the capillary endothelial cells and retinal pigment epithelial cells produce basic FGF in vitro. It seems that FGF effects those cells in an autocrine or paracrine manner in vivo.

Animals↗
PubMed1995

Extravascular secretion of t-PA by the intact superfused choroid.

PURPOSE: Demonstrate the continuous extravascular secretion of enzymatically active t-PA by the intact choroid. METHODS: Enucleated rat eyes were dissected under microscopic control to prepare eyecups for superfusion in a small organ culture system. Individual preparations provided access to intact retinal, retinal pigment epithelial, or choroidal surfaces in situ. Cups were superfused with oxygenated Kreb's buffer (100 microliters/minute) at 37 degrees C and pH 7.4 while suspended in a microincubator. Released t-PA activity was measured by an amidolytic assay in 1-minute overflow samples and in cup media after flow interruptions. RESULTS: Minimal basal secretion was detected in the overflow with the retina in place. Interruption of flow (10 minutes) produced a static accumulation of 0.10 +/- 0.01 IU/ml. With the retinal pigment epithelium in place after retinal removal, t-PA release was moderately accelerated. Removal of the retinal pigment epithelium to expose the Bruch's-choroidal surface produced the greatest acceleration. The 10-minute static level was 0.48 +/- 0.13 IU/ml. Release from the scleral shell after choroid removal was negligible. An acute burst release of t-PA activity (1.3 +/- 0.18 IU/ml) followed the infusion of bradykinin (5 to 20 microM) into choroidal cups. CONCLUSION: Choroid appears to be the dominant source of a continuously secreted t-PA in superfused rat eyecup organ cultures. This enzymatically active t-PA is able to pass through an apparently intact Bruch's membrane but is largely impeded by an intact retinal pigment epithelium. It is also possible that retinal pigment epithelium contains inhibitors that could reduce the released t-PA activity. The authors propose that this secretory function of the uveal tissue, which has thus far not been recognized, may be a principal mechanism for the regulation of intraocular fluid circulation and matrix remodeling by plasmin in vivo.

Animals↗
PubMed1995

The effect of N-ethylmaleimide on the Na(+)-dependent nucleoside transporter (N3) in rabbit choroid plexus.

The effect of the irreversible sulfhydryl-modifying agent, N-ethylmaleimide (NEM), on the transport of purine and pyrimidine nucleosides in choroid plexus was examined. [3H]thymidine and [3H]guanosine were used as model compounds to determine the effect of NEM on the Na(+)-dependent nucleoside transporter (N3) in rabbit choroid plexus tissue slices that were ATP-depleted with 2,4 dinitrophenol. Thymidine uptake in choroid plexus tissue slices preincubated with NEM was irreversibly inhibited in a concentration- (IC50 = 0.18 mM) and time-dependent fashion. NEM treatment also reduced the Na(+)-dependent uptake of other purine and pyrimidine nucleosides to a similar extent. In addition, an amine-selective modifying reagent, phenylisothiocyanate, had no effect on Na(+)-dependent thymidine uptake. Treatment of choroid plexus tissue slices with other sulfhydryl-modifying agents, including 4,4-dithiodipyridine, a reagent specific for cysteine residues, reduced the Na(+)-dependent uptake of thymidine. Preincubation of choroid plexus slices with NEM (2.5 mM) increased the Km of guanosine (control 64.5 +/- 5.7 microM; treated 120 +/- 23 microM) whereas the Vmax was unaffected (control 4.7 +/- 1 nmol/g/sec; treated 4.03 +/- 0.26 nmol/g/sec). These data suggest that covalent modification of sulfhydryl groups reduces the Na(+)-dependent uptake of nucleosides in choroid plexus slices by decreasing the affinity of nucleosides for the transporter.

Animals↗
PubMed1995

Ocular perfusion pressure and choroidal blood flow in the rabbit.

PURPOSE: To compare choroidal blood pressure versus flow relationships obtained by three different methods of changing the ocular perfusion pressure. METHODS: Experiments were performed in pentobarbital-anesthetized rabbits with occluders on the aorta and inferior vena cava to control mean arterial pressure (MAP). The central ear artery was cannulated to measure MAP. Two 23-gauge needles were inserted through the pars plana into the vitreous: one connected to a saline-filled syringe to vary the ocular volume and the other to a pressure transducer to measure intraocular pressure (IOP). Choroidal perfusion was measured by laser-Doppler flowmetry with the probe in the vitreous over the posterior pole. In group 1 (n = 15), the MAP was varied while holding the IOP at 10, 15, 20, 25 and 30 mm Hg. In group 2 (n = 19), the IOP was increased while holding the MAP at 80, 70, 60, 50, 40, 30 and 20 mm Hg. In group 3 (n = 21), the MAP was varied without controlling the IOP. RESULTS: Group 1 baseline choroidal flows were similar at the five IOPs. When the flow was plotted against MAP, the curves diverged and extrapolated to intersect the pressure axis when the MAP equaled the set IOP. Group 2 baseline flows were similar at MAPs greater than 40 mm Hg. When the flow was plotted against the IOP, the curves diverged and intersected the pressure axis when the IOP equaled the MAP. In both groups, plotting the flow against the perfusion pressure (i.e., MAP minus IOP) collapsed the data points into single curves. Choroidal autoregulation occurred in all three groups; however, the low end of the autoregulatory perfusion pressure range was approximately 50 mm Hg in group 1, approximately 40 mm Hg in group 2, and approximately 30 mm Hg in group 3. CONCLUSIONS: The results show that the effective choroidal perfusion pressure gradient equals the MAP minus the IOP, and that choroidal autoregulation is most effective when the MAP varies and IOP is not controlled.

Animals↗
PubMed1994

Placental lactogen binding sites in the pregnant rabbit choroid plexus.

Prolactin has direct effects on the CNS. The highest concentration of prolactin receptors resides within the choroid plexus where they probably function to transport prolactin from blood into CSF. Another member of the lactogen family of hormones, placental lactogen (PL), also affects CNS activity and may similarly employ the cerebroventricular system as an intermediary. In order to determine whether the choroid plexus was a PL target tissue, in vitro autoradiography was used to identify specific PL binding sites in the choroid plexus of pregnant New Zealand White rabbits. Frozen brain sections were incubated in a medium containing 125I human PL (hPL) alone (total binding) or with a 500-fold excess of unlabelled hPL (nonspecific binding). The specificity of the binding was assessed with unlabelled human growth hormone (hGH) and ovine luteinising hormone (oLH). An intense autoradiographic reaction occurred over the choroid plexus of tissue sections incubated with 125I hPL alone. Excess unlabelled hPL and hGH, which is lactogenic in the rabbit, caused a significant reduction (P < 0.001) in the binding of radiolabelled hPL to the choroid plexus. In contrast, unlabelled oLH had no effect on radiolabelled hPL binding to this tissue. The results support a role for the choroid plexus in the interactions between PL and the CNS.

Animals↗
PubMed1993

Diagnosis and differential diagnosis of malignant melanomas of the choroid.

A complete ocular examination is essential for the correct diagnosis of a malignant melanoma of the choroid. The single, most important technique is indirect ophthalmoscopy associated with biomicroscopy of the fundus. Fluorescein angiography may provide additional arguments for malignancy, but with this method it is not always possible to differentiate a malignant melanoma from a suspected naevus or even a choroidal metastasis. Fluorescein angiography provides however a detailed and objective document which allows a better follow-up of suspected lesions. As with infrared angiography, choroidal vessels are more readily seen, this technique may prove to be of diagnostic importance. A- and B-scan ultrasonography are essential to precisely measure a choroidal lesion. Especially A-scan may also allow tissue differentiation. Diaphanoscopy is especially useful in the diagnosis of choroidal haemangioma. Even naevi may provide relative or absolute scotomas. The diagnostic importance of perimetry is therefore very limited. CT-scan and especially MRI are helpful in detecting extra-ocular extension. In case of atypical naevi, a close observation for potential growth is advised. Malignant melanomas of the choroid have to be differentiated from other fundus tumours, but also from inflammatory and degenerative conditions.

Aged↗
PubMed1994

[Hypertensive choroid angiography. Initial results].

A new method for the examination of choroidal morphology and hemodynamics by SLO-ICG videoangiography under induced hypertension by ocular ophthalmodynamography is presented. In 17 normal subjects, 32 patients suffering from exudative age-related macular degeneration and 13 patients suffering from subretinal fibrosis, the arterial blood vessels of the choroid were demonstrated in detail angiographically. Perfusion pressures of posterior ciliary arteries at their entry into the eye were also estimated. In the majority of patients in each group the central retinal artery was first filled with dye; in the central 40 degrees field 5-8 posterior ciliary arteries were detected; the arterial branches of the submacular choroid were supplied by a submacular ciliary artery in more than half of the cases; however, dye filling of the submacular choroid occurred later than in the surrounding choroid during reduction of intraocular pressure. ICG fluorescence angiography is compared to other angiographic examination methods of choroidal morphology and hemodynamics.

Adult↗
PubMed1993

Differential expression of Na,K-ATPase alpha and beta subunit isoforms at the blood-brain barrier and the choroid plexus.

The relative levels of expression of Na,K-ATPase alpha and beta subunit isoforms were determined in rat cerebral microvessels, choroid plexus, and capillary-depleted brain homogenates by Western blot analysis. Three alpha (alpha 1, alpha 2, alpha 3) and two beta (beta 1, beta 2) subunits were detected in brain as previously reported. All 3 alpha and 2 beta isoforms were also found in microvessels. The choroid plexus expressed alpha 1, beta 1, and beta 2, while alpha 2 and alpha 3 were not found. Autoradiographic signals were normalized to a constant amount of protein from the 3 tissues to calculate relative levels of expression. Expression of alpha 1, alpha 2, and alpha 3 was higher in microvessels than in the brain, by 1.7-, 1.2-, and 1.2-fold, respectively, but expression of beta 1 and beta 2 was 5.5-fold lower. alpha 1 was 4-fold higher in the choroid plexus than in the brain, while expression of beta 1 and beta 2 was 15- and 5.5-fold lower, respectively. Na,K-ATPase enzymatic activities in microvessels and choroid plexus homogenates were similar and 5-fold lower than in brain homogenate. We conclude that: (a) expression of functionally active Na,K-ATPase isoenzymes in microvessels and choroid plexus is restricted in comparison to the brain possibly due to a limited pool of beta 1 and beta 2 subunits; (b) six structurally distinct Na,K-ATPase isoenzymes may be expressed in cerebral microvessels and two in the choroid plexus.

Animals↗
PubMed1996

Adrenergic modulation of choroidal blood flow in the rabbit.

PURPOSE: To determine whether the choroidal pressure-flow is altered by the alpha-adrenergic antagonist, phentolamine, or the beta-adrenergic antagonist, propranolol. METHODS: In two groups of pentobarbital- anesthetized rabbits, the choroidal pressure-flow relationships were determined by raising the intraocular pressure (IOP) at mean arterial pressure (MAP) of 50, 60, 70, and 80 mm Hg before and after phentolamine (0.5 mg/kg, intravenously, n=7) and propranolol (0.25 mg/kg intravenously, n=7) administration. Hydraulic occluders on the thoracic aorta and inferior vena cava were used to control MAP, which was measured in the central ear artery. The eye was cannulated with two 23-gauge needles, one to manipulate the ocular volume and the other to measure the IOP. Choroidal blood flow was measured by laser Doppler flowmetry with a probe positioned over the posterior retina. The protocol consisted of setting the MAP, then infusing saline into the eye at 30 microliters/minute until the IOP increased from baseline to 100 mm Hg. RESULTS: At the MAP of 70 mm Hg, alpha-adrenergic blockade caused an upward shift in the choroidal pressure-flow relationship; beta-blockade shifted the relationship downward. CONCLUSIONS: In the pentobarbital-anesthetized rabbit, alpha- and beta- adrenergic blockade cause choroidal vasodilation and vasoconstriction, respectively. Results indicate the presence of alpha- and beta-adrenergic receptors in the rabbit choroid and a tonic level of adrenergic vascular tone in this preparation.

Adrenergic alpha-Antagonists↗
PubMed1996

MIB-1 immunoreactivity reveals different labelling in low-grade and in malignant epithelial neoplasms of the choroid plexus.

MIB-1 immunohistochemistry was carried out on a retrospective biopsy series of epithelial choroid plexus neoplasms in order to assess the proliferation rate of tumour cells. The material included 14 cases of papilloma (WHO grade I) and five cases of carcinoma (WHO grade III). There was one recurrent tumour in the papilloma group, while three patients with carcinoma experienced recurrence. Choroid plexus obtained at autopsy from paediatric and adult patients with unrelated diseases served as control. The average MIB-1 labelling index of choroid plexus papillomas was 3.7%, while that of carcinomas was 14%, and that of normal choroid plexus was 0.02% to 0.06%. The age and sex of the patients as well as the tumour localization were not found to influence MIB-1 reactivity. The labelling index of recurrent lesions was not significantly different from that of the corresponding primary tumours. High MIB-1 labelling indices were associated with less favourable post-operative outcome in choroid plexus carcinomas and in one papilloma with atypical histology. However, most tumours with atypical histological features did not exhibit distinctive MIB-1 labelling indices. Analysis of growth fraction by MIB-1 immunohistochemistry may prove a useful ancillary method for assessing the malignant potential of choroid plexus neoplasms.

Adolescent↗
PubMed1996

[Indocyanine green infrared fluorescence angiography and vascular cast--preparation in experimental choroidal circulatory disturbance].

We performed experiments in 20 monkey eyes in order to clarify basic problems about interpretation of indocyanine green fluorescence angiography (ICG angiography). We severed the temporal group of posterior ciliary arteries to produce choroidal circulatory disturbance. ICG angiography was performed immediately, and 2 days, 4 days, and 2 weeks later. Following each ICG angiography, the eye was studied by plastic vascular cast technique with scanning electron microscopy. Immediately after occlusion, ICG angiography showed filling defect in the temporal choroidal hemisphere during the early phase. In the later phase, this area was gradually filled by the dye from choroidal arteries in the nasal hemisphere and the anterior ciliary arteries. Vascular cast preparations showed filling defect in the temporal choroidal hemisphere, corresponding with the early ICG angiogaphic findings. Both filling delay in ICG angiography and filling defect in vascular casts improved daily after occlusion. Two weeks after occlusion, The area of choroidal infarct temporal to the macula turned into chorioretinal atrophy. This area showed hypofluorescence in the early-phase ICG angiography and filling defect of the choriocapillaris in plastic casts. The early-phase ICG angiographic findings thus corresponded well with observations of vascular casts. We conclude that ICG angiography correctly reflects the actual circulatory disturbances in the choroid.

Animals↗
PubMed1997

[Effects of endothelin-1 on choroidal vessels--1. Study with the scleral window technique].

The effects of topical administration of endothelin-1 (ET-1), a potent and long-acting vasoconstrictive peptide, on choroidal vessels were studied in albino rabbits. In enucleated eyes that were divided and the retinas removed, topical instillation of ET-1 at 5 x 10(-5)M induced remarkable constriction of choroidal arteries and veins. In vivo, the scleral window technique and microcinematography were used to study the effects of ET-1 on the choroidal arteries. The same field was recorded before, and 15 and 30 minutes after, instillation of 2 microliters of ET-1 at 5 x 10(-5)M every 5 minutes. Topical application of ET-1 did not cause any statistically significant change in caliber of the choroidal arteries either in the untreated group or in the ganglionectomy group (superior cervical sympathetic ganglions were removed and choroidal arteries were dilated). These results suggest that ET-1 acts in choroidal arteries from the retinal side in vitro but does not act from the scleral side in vivo.

Administration, Topical↗