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Subretinal neovascularization with geographic (serpiginous) choroiditis.

Three patients with geographic choroiditis developed subretinal neovascular membranes associated with subretinal hemorrhage and serous elevation of the retina. Proximity of the membrane to the foveal avascular zone prevented photocoagulation of the neovascular membrane in one patient. Central visual acuity remained 6/60 (20/200) despite systemic corticosteroid therapy. The neovascular membranes in the other two patients were obliterated by argon laser photocoagulation with preservation of central vision. The inflammatory process of geographic choroiditis can disrupt Bruch's membrane, allowing occasional choroidal vascular growth. Concomitant destruction of choroidal vessels may account for rarity of subretinal neovascularization in geographic choroiditis.

Aged↗

Choroidal blood flow as a heat dissipating mechanism in the macula.

We studied the possible role of the choroidal circulation in stabilizing the temperature environment of the retina and the retinal pigment epithelium. Temperature measurements were taken from the retina and choroid of the monkey eye while the ambient illumination and choroidal blood flow were varied. The results showed that the choroidal circulation plays a significant role in dissipating heat generated by the focusing of light at the macula and suggest that this function may be a primary reason for the relatively high values of choroidal blood flow.

Animals↗

Alteration of sodium transport by the choroid plexus with amiloride.

Cerebrospinal fluid (CSF) production results from active transport of Na+ from blood to CSF, which is followed by H2O and anions. Amiloride reduces Na+ movement in epithelial tissues. To ascertain if amiloride alters transport of Na+ in the choroid plexus, the drug was administered either i.p. to male Sprague-Dawley rats that were bilaterally nephrectomized to determine in vivo effects, or added to artificial CSF to incubate the choroid plexus in vitro. Choroid cell [Na+] was reduced after amiloride treatment both in vivo and in vitro. In addition, the rate of 22Na uptake into the CSF and choroid plexus (CP) was decreased after amiloride. Alterations in choroid cell [Na+] and 22Na penetration into CSF and CP occurred at relatively high doses of drug (1 mumol/ml, in vitro and 100 micrograms/g in vivo), but lower doses were less effective (0.1 mumol/ml in vitro and 10 micrograms/g in vivo). It is concluded that the effects of amiloride on Na+ distribution and transport in the CP are due to inhibition of basolateral Na+-H+ exchange.

Amiloride↗

The uptake of delta9-tetrahydrocannabinol in choroid plexus and brain cortex in vitro and in vivo.

[3H]delta9 Tetrahydrocannabinol (delta9-THC) was actively transported by the choroid plexus and cerebral cortical slices of the rabbit when incubated as a BSA-microsuspension in artificial rabbit CSF. The transport system for delta9-THC in choroid plexus had a V max of 174 nmoles/mg tissue/h, approximately 9-fold greater than that observed for cortical slices. In vivo experiments demonstrated a preferential distribution of delta9-THC in choroid plexus at 1 h after intravenous injection. These results indicate that delta9-THC is actively accumulated by choroidal epithelium and may also be transported across the epithelial stroma into the capillary circulation. This suggests that the choroid plexus participates in the regulation of delta9-THC concentration in CSF and indirectly in brain by means of the "sink" function of the CSF.

Animals↗

Choroid plexus blood flow: evidence for dopaminergic influence.

Choroid plexus blood flow was measured in adult female sheep using the radioactive microsphere technique. The response of choroid plexus, renal and cortical blood flow to the infusion of dopamine (11 sheep), haloperidol (7 sheep) and propranolol (6 sheep) were compared. Choroid plexus and renal blood flow significantly increased after dopamine infusion (55% and 49% respectively). Choroid plexus and renal blood flow decreased significantly following haloperidol infusion (-24% and 29% respectively). Cortical blood flow did not significantly change. Propranolol infusion did not significantly change blood flow in these regions. These observations suggest that dopaminergic mechanisms play a role in the regulation of choroid plexus as well as renal blood flow.

Animals↗

Serotonin-1C sites in the choroid plexus are not linked in a stimulatory or inhibitory way to adenylate cyclase.

The association of the serotonin recognition sites in the pig choroid plexus (5-HT-1C sites) with an adenylate cyclase was examined. The interaction of serotonin and mianserin with [3H]mesulergine binding was not affected by the stable GTP analogue GppNHp. The binding of [3H]serotonin to choroid plexus membranes was also unaffected by GppNHp while a dose-dependent decrease was observed in pig cortical and hippocampal membranes. The porcine choroid plexus contained a forskolin- and histamine-sensitive adenylate cyclase. Serotonin, however, was ineffective in this preparation. While forskolin-stimulated adenylate cyclase in the rat hippocampus was inhibited by serotonin forskolin-stimulated adenylate cyclase in the choroid plexus was insensitive to serotonin. These results indicate that the serotonin recognition sites in the choroid plexus are not linked in a stimulatory or inhibitory way to an adenylate cyclase, in contrast with other 5-HT-1 receptor subtypes.

Adenylyl Cyclases↗

Cerebrospinal fluid calcium homeostasis: evidence for a plasma membrane Ca2+-pump in mammalian choroid plexus.

A major unanswered question in central nervous system physiology concerns the mechanism by which cerebrospinal fluid (CSF) Ca2+ homeostasis is maintained in the face of hypo- or hypercalcemia. To address this question, we sought and found a protein of Mr approximately 140,000 in choroid plexus plasma membranes that forms a phosphorylated intermediate with characteristics of a plasma membrane Ca2+-pump. A choroid plexus plasma membrane protein of this molecular weight also bound to a monoclonal antibody prepared against the human erythrocyte plasma membrane Ca2+-Mg2+ ATPase Ca2+-pump. When this monoclonal antibody was used for immunohistochemical localization, the plasma membrane Ca2+-pump was found primarily in the CSF-facing membranes of choroid plexus cells from rats, cats, and man. The localization of a plasma membrane Ca2+-pump in the CSF-facing membranes of the choroid plexus suggests that the choroid plexus, by mechanisms including this pump, may regulate CSF Ca2+ concentrations.

Animals↗

Kinetic analysis of L-carnitine uptake by the choroid plexus.

Choroid plexuses from the lateral (LVCP) and fourth ventricles (FVCP) of rats or rabbits were incubated in artificial cerebrospinal fluid (CSF) containing 1 microM [14C]L-carnitine with various concentrations of L-carnitine ranging from 0.01 mM to 1.0 mM. The time course of 1 microM [14C]L-carnitine uptake by the choroid plexus indicated that it increased linearly for the first 15 min. Steady-state levels were reached by 30 min with tissue concentrations more than 20 (FVCP)- to 30 (LVCP)-fold greater than the concentration in the medium. The uptake of [14C]L-carnitine was increased with increasing concentrations of the substrate in the medium and this uptake followed Michaelis-Menten kinetics. The uptake by the rat choroid plexus took place against a concentration gradient via a saturable process and kinetic analysis revealed Km of 32 microM (LVCP) and 34 microM (FVCP) and Vmax of 21 (LVCP) and 17 nmol/ml/min (FVCP), respectively. Ouabain inhibited the uptake by 51% (FVCP) and 48% (LVCP) and hypothermia (0 degrees C) produced inhibition by 97% (FVCP) and 96% (LVCP), respectively. However, the uptake of L-carnitine was not sensitive to probenecid or tyrosine, which indicates the presence of an independent carrier for L-carnitine in the choroid plexus. Similar results were obtained with the rabbit choroid plexus.

Animals↗

Angiotensin-converting enzyme: presence of high activity in choroid plexus of mammalian brain.

The activity of angiotensin-converting enzyme in rat choroid plexus was higher than that of any other organ, being 6--7 times higher than that in lung and more than 50 times higher than in any other region of brain. Rabbit choroid plexus also had high activity of enzyme while that of human choroid plexus was relatively low. The enzyme in rat choroid plexus showed similar biochemical properties to that in other tissues; it was inhibited by the nonapeptide SQ 20,881, by (Sar1-Ala8)-angiotensin II and by EDTA, and required chloride ions for activity. As in other tissues, the choroid plexus enzyme was associated with particulate fractions after differential centrifugation. The corpus striatum and substantia nigra had the highest activities in the various brain regions examined.

Animals↗

A comparison of the elastic properties of human choroid and sclera.

Multiple strips of choroid (56) and sclera (64) from eight pairs of human eye-bank eyes were subjected to simple tension in a test apparatus to determine the rigidity (modulus of elasticity) of these tissues. The modulus of elasticity of the chorodial complex (choroid-Bruch's membrane-pigment epithelium) was significantly greater in posteriorly located samples than in anteriorly located ones (7.5 +/- 7.0 vs. 2.2 +/- 1.5 x 10(5) N m-2, mean +/- S.D.). The modulus of elasticity for the complex averaged across all locations was 6.0 +/- 2.8 x 10(5) N m-2 and the average stress at failure was 3.3 +/- 1.3 x 10(5) N m-2. The modulus of elasticity for scleral strips also varied with location and averaged 2.9 +/- 1.4 x 10(6) N m-2 for anterior sclera and 1.8 +/- 1.1 x 10(6) N m-2 for posterior sclera at stress levels ranging from 20- to 260 x 10(4) N m-2. There was a significant correlation of scleral stiffness with age (P less than 0.05, r = 0.80). The elastic properties of the choroidal complex may be relevant to the pathogenesis of a variety of ocular diseases, including macular degeneration, angioid streaks, choroidal folds, and choroidal ruptures.

Adolescent↗

The management of small choroidal melanomas.

There are a number of unresolved questions regarding small choroidal melanomas. At what stage in the natural history of these tumors do they develop the capacity to metastasize? What are the effects of various therapeutic modalities on the incidence of metastatic disease? Clinicopathologic studies suggest that patients with small choroidal melanomas (less than 10 mm in diameter and 3 mm in height) have an excellent prognosis. In patients with small choroidal melanomas with clear ocular media and no clinical retinal detachment, it is reasonable to do serial examinations without therapeutic intervention until growth is documented. In patients with small choroidal melanomas in which growth is documented, enucleation or alternate modes of therapy, including photocoagulation or radiation, are reasonable methods of treatment. Only by conducting prospective studies can we obtain a better understanding of the natural history of choroidal melanomas, determine at what stage these small lesions develop a metastatic potential, and evaluate the relative efficacy of various treatment modalities in preventing the development of metastatic disease.

Choroid Neoplasms↗

Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks.

It is known that when hyperopic or myopic defocus is imposed on chick eyes by spectacle lenses, they rapidly compensate, becoming myopic or hyperopic respectively, by altering the depth of their vitreous chamber. Changes in two components--ocular length and choroidal thickness--underlie this rapid compensation. With monocular lens treatment, hyperopic defocus imposed by negative lenses resulted in substantially increased ocular elongation and a slight thinning of the choroid, both changes resulting in myopia; myopic defocus imposed by positive lenses resulted a dramatic increase in choroidal thickness, which pushed the retina forward toward the image plane, and a slight decrease in ocular elongation, both changes resulting in hyperopia. The refractive error after 5 days of lens wear correlated well with vitreous chamber depth, which reflected the changes in both choroidal thickness and ocular length. The degree of compensation for lenses was not affected by whether the fellow eye was covered or open. Both form-deprivation myopia and lens-induced myopia declined with age in parallel, but wearing a -15 D lens produced more myopia than did form deprivation. The spectacle lenses affected the refractive error not only of the lens-wearing eye, but also, to a much lesser degree, of the untreated fellow eye. At lens removal refractive errors were opposite in sign to the lense worn, and the subsequent changes in choroidal thickness and ocular length were also opposite to those that occurred when the lenses were in place. In this situation as well, effects of the spectacle lenses on the fellow eyes were observed. Eyes with no functional afferent connection to the brain because of either prior optic nerve section or intraocular tetrodotoxin injections showed compensatory changes to imposed defocus, but these were limited to compensation for imposed myopic defocus, at least for the eyes with optic nerve section. In addition, optic nerve section, but not tetrodotoxin treatment, moved the set-point of the visual compensatory mechanism toward hyperopia. Optic nerve section prevents myopia in response to negative lenses but not to diffusers, suggesting that compensation for hyperopia requires the central nervous system.

Animals↗

Enzyme histochemistry of the choroid plexus in old rats.

The influence of ageing on the metabolic profile of lateral ventricle choroid plexus epithelial cells from young (3-month-old) and aged (26-month-old) male Wistar rats was studied using enzyme histochemical techniques. The following enzymatic activities related to energy transduction were examined: lactate-(LDH) and succinate- (SDH) dehydrogenases; NADH2-tetrazolium reductase (NADHD) and alpha-glycerophosphate-dehydrogenase (GPDH). The intensity of enzymatic staining within single choroid plexus epithelial cells from young and old animals was assessed microphotometrically. In the choroid plexus epithelial cells of young rats NADHD was the enzymatic activity more heavily stained; cell levels of LHD and GPDH were approximately the same and SDH reactivity was less intense. In old age LDH was reduced by 9.3%, SDH was reduced by 26.1%, NADHD was reduced by 8.6% and GPDH was reduced by 3.6%. The possibility that impaired energy transduction mechanisms at the level of choroid plexus epithelium in old age may influence functional activity of the choroid plexus is discussed.

Aging↗

Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine.

Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.

Animals↗

Gene expression and secretion of insulin-like growth factor-II and insulin-like growth factor binding protein-2 from cultured sheep choroid plexus epithelial cells.

The gene expression of insulin-like growth factor II (IGF-II) and insulin-like growth factor binding protein-2 (IGFBP-2) has previously been demonstrated in rat and human choroid plexus by in situ hybridization analysis. In the present study we have characterized IGF-II and IGFBP-2 transcripts and proteins in primary cultures of epithelial cells from lateral choroid plexus of sheep brain. Northern blot analysis of total RNA showed one major IGF-II mRNA of 4.8 kb and four minor IGF-II transcripts of 1.5, 2.0, 3.0 and 6.0 kb as well as one IGFBP-2 transcript of 1.7 kb. Radioreceptor assay of conditioned medium from the cultured choroid plexus epithelial cells showed inhibition of [125I]IGF-I and [125I]IGF-II binding to mouse NIH 3T3 fibroblasts, the displacement curves being identical to that of unlabelled IGF-II. The conditioned medium was fractionated by gel filtration on a Bio-Gel P-60 column, and analysis by IGF-II radioreceptor assay showed two peaks of IGF-II-binding inhibitory activity of M(r) 7.5-10 and 25 kDa, suggesting the presence of both IGF-II, and an IGFBP. Western immunoblot analysis of conditioned medium with antibodies toward IGF-II and IGFBP-2 demonstrated proteins with M(r) 6 kDa and 32 kDa, respectively. Protein binding assays of the conditioned medium with [125I]IGF-I or [125]IGF-II demonstrated that the IGFBP present in the conditioned medium preferentially binds IGF-II. In conclusion, cultured sheep choroid plexus epithelial cells synthesize and secrete IGF-II and IGFBP-2, suggesting that the choroid plexus epithelium is the main source of these polypeptides in the cerebrospinal fluid.

3T3 Cells↗

Evidence for increased calcium influx across the choroid plexus following brief ischemia of gerbil brain.

Following 5 min ischemia of gerbil brain, unidirectional transfer of calcium from plasma to cerebrospinal fluid was measured quantitatively with 45CaCl2 at 4 days postischemic recirculation. 45Ca influx across the choroid plexus increased significantly from 0.0101 +/- 0.001 min-1 measured in sham-operated animals (n = 15) to 0.0294 +/- 0.002 min-1 determined in ischemic animals (n = 21; P less than 0.05). Histological examination of choroid plexus was carried out in Cresyl violet-stained sections from gerbils subjected to 5 min ischemia followed by 4 days (n = 6) and 7 days (n = 7) postischemic recirculation. Increased calcium transfer to cerebrospinal fluid was associated with cell damage of choroid plexus observed at 4 days postischemia. Endothelial choroid plexus injury was still detectable at 7 days after the ischemic insult suggesting a long-lasting pathomorphological process. Postischemic alterations in choroid plexus functions apparently expose brain tissue to much higher calcium influx into cerebrospinal fluid which, in turn, may contribute to calcium-related cell damage of the central nervous system.

Animals↗

Induction and immunological characterization of the uridine diphosphate-glucuronosyltransferase conjugating 1-naphthol in the rat choroid plexus.

The uridine diphosphate-glucuronosyltransferase isoform conjugating 1-naphthol has a very high activity in the rat choroid plexus. We showed that antibodies raised against the main liver isoenzyme cross-reacted with a choroidal protein exhibiting the same molecular weight as the hepatic form. Both enzymes had a similar affinity for 1-naphthol. After an in vivo treatment by 3-methylcholanthrene, a 3-fold increase of the activity in both the liver and choroid plexuses was observed. These results suggest that the choroidal and hepatic enzymes conjugating 1-naphthol are identical. This high metabolic activity suggests a metabolic protection of the brain by the choroid plexus.

Animals↗

Transthyretin (prealbumin) gene expression in choroid plexus is strongly conserved during evolution of vertebrates.

1. The major protein synthesized and secreted by the choroid plexus from mammals, birds, reptiles and probably amphibians is similar in subunit structure to transthyretin. 2. In mammals and birds the proportion of transthyretin mRNA is much higher in choroid plexus RNA than in liver RNA. No transthyretin mRNA is found in brain outside the choroid plexus. 3. Transthyretin-like protein, such as that secreted by the choroid plexus, was not detected in amphibian serum and was present in very low levels in reptile serum. 4. It is proposed that transthyretin synthesis and secretion arose earlier in evolution in the choroid plexus than in the liver.

Animals↗