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Detection of choroidal calcium by computed tomography scan quantitative computerized tomography: a clinically useful diagnostic tool.

OBJECTIVE: Quantitative computerized tomography (QCT), a scanning method routinely used to classify tissues based on their radio density, was used to detect choroidal calcification. DESIGN: Case reports. PARTICIPANTS: Two patients with known or suspected choroidal calcium-choroidal osteoma (CO) and pseudoxanthoma elasticum (PXE) and five normal control subjects were assessed. INTERVENTION: The CT scan of choroid, B-scan ultrasound, fluorescein angiography. MAIN OUTCOME MEASURES: The QCT scan used to detect the presence of calcium based on a readout greater than 90. RESULTS: Calcium was detected bilaterally, as predicted, in PXE, and in both eyes of CO, although only one eye had a clinically noted lesion. No control eye gave a scale readout consistent with calcium. No findings suggestive of calcium were noted with B-scan ultrasound or fluorescein angiography in PXE or CO. CONCLUSION: The QCT can detect calcium in the choroid when B-scan ultrasonography and CT scan fine sectioning fail to identify calcium despite high clinical suspicion.

Adult↗

Perinatal changes in choroidal 15-hydroxyprostaglandin dehydrogenase: implications for prostaglandin removal from brain.

We have previously shown in the sheep fetus at 0.7 and 0.9 gestation that the choroid plexus, unlike brain parenchyma, catabolizes prostaglandins (PGs). Peculiarly, in the choroid plexus, PGE(2) catabolism persists throughout the neonatal period to abate in the adult, while PGF(2alpha) catabolism abates shortly after birth. To explain this differential behavior and elucidate the function of catabolic enzymes, we examined the cellular location and activity of the rate-limiting enzyme for PGE(2) and PGF(2alpha) catabolism, 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Immunofluorescence histochemistry and immunogold electronmicroscopy revealed abundant 15-PGDH expression in the epithelial cytosol close to the brush-border membrane at 0.7 and 0.9 gestation. In contrast, at 5 and 15 days postnatal, 15-PGDH was found throughout the cytosol of stromal fibroblasts. No staining was observed at either location in pregnant adults. PGF(2alpha) catabolism was minimal in the total homogenate and 100000xg supernatant of the fetal choroid plexus at 0.7 and 0.9 gestation, while PGE(2) catabolism was evident at 0.7 gestation only. In contrast, both PGs were catabolized in minced specimens at either age. In conclusion, our study shows immunoreactive 15-PGDH in the choroid plexus from fetal and neonatal, but not pregnant adult, sheep. Results suggest that PGE(2) catabolism is not as critically dependent as that of PGF(2alpha) on tissue integrity and 15-PGDH location. Given the key role being assigned to the choroid plexus in PG removal from brain, we speculate that persistence of PGE(2) catabolism into the early postnatal period protects against central respiratory depression caused by the compound during this susceptible stage of development.

Age Factors↗

Comparative genomic hybridization detects specific cytogenetic abnormalities in pediatric ependymomas and choroid plexus papillomas.

Pathogenesis and genetic abnormalities of ependymomas are not well known and differential diagnosis with choroid plexus tumors may be difficult when these tumors are located in the ventricles. We analyzed 16 samples of primary pediatric ependymomas and seven choroid plexus tumors for significant gains or losses of genomic DNA, using comparative genomic hybridization (CGH). Four ependymoma samples were obtained after surgery for relapse, including one patient whose tumor was analyzed at diagnosis and at first and second relapses. Three out of 16 ependymomas and none of the choroid plexus tumors appeared normal by CGH. In the remaining ependymomas, the number of regions with genomic imbalance was limited. The most frequent copy number abnormality in ependymomas was 22q loss. In one patient from whom multiple samples could be analyzed during tumor progression, no abnormality was present at diagnosis; gain of chromosome 9 and loss of 6q were observed at first relapse and, at second relapse, additional genomic imbalances were loss of 3p, 10q, and chromosome 15. In choroid plexus tumors, recurrent abnormalities were gains of chromosome 7 and region 12q. The recurrent chromosomal abnormalities were clearly different between ependymomas and choroid plexus papillomas (CPP). Recurrent loss of 22q suggests that this region harbors tumor suppressor genes important in the pathogenesis of ependymomas; however, other pathogenic pathways may exist involving 6q and chromosome 10 losses or gain of 1q and chromosome 9. CPP can be distinguished from ependymoma on the basis of CGH abnormalities.

Brain Neoplasms↗

The presence of arginine vasopressin and its mRNA in rat choroid plexus epithelium.

Arginine vasopressin (AVP) plays an important role in the regulation of secretory function and hemodynamics of choroid plexus, the primary site of cerebrospinal fluid (CSF) production. In the present study, localization of AVP and its transcripts in choroid plexus of adult male Sprague-Dawley rats was studied by immunohistochemistry and in situ hybridization histochemistry, respectively. For immunohistochemical analysis, AVP-specific polyclonal rabbit antibody was employed. Plasmid, pGrVP, containing a 232-bp fragment of rat AVP cDNA encoding the C-terminus of proAVP, was used as a probe to detect AVP mRNA. AVP-immunoreactive product was predominantly localized close to the apical (CSF-facing) membrane of choroidal epithelium while AVP transcripts were distributed throughout the cytoplasm of the cells. Our findings indicate that AVP is synthesized in choroid plexus epithelium, which suggests autocrine and/or paracrine actions of this peptide in choroidal tissue.

Animals↗

Identification and expression of the Na+/H+ exchanger in mammalian cerebrovascular and choroidal tissues: characterization by amiloride-sensitive [3H]MIA binding and RT-PCR analysis.

We report the initial characterization of [3H]5-(N-methyl-N-isobutyl)amiloride (MIA) binding to the Na+/H+ exchanger (NHE) and expression of its gene in mammalian cerebrovascular, choroidal and neocortical tissues. [3H]MIA bound reversibly to particulate fractions of rat, pig and human cerebral microvessels, choroid plexus and cerebral cortex. Scatchard analyses revealed binding to a single amiloride-sensitive site with dissociation constants (Kd) ranging from 20 to 90 nM for the various tissue preparations. The maximal binding capacities (Bmax) were between 2 to 17 pmol/mg protein and were several-fold greater in cerebral microvessels compared to the cerebral cortex. Amiloride, MIA, 5-(N, N-hexamethylene)amiloride (HMA), 5-(N, N-dimethyl)amiloride (DMA) and 5-(N-methyl-N-isopropyl)amiloride (IPA) variably displaced [3H]MIA binding to the microvessels in the following rank order: MIA>HMA>/=IPA>DMA>amiloride. Benzamil, a potent ligand of the Na+/Ca+ transporter was the least sensitive. These binding results were most compatible with the existence of the amiloride-sensitive NHE type 1 in the brain vascular and choroidal tissues. To substantiate this, we utilized reverse transcription polymerase chain reaction (RT-PCR) techniques to search for NHE-1 mRNA. Using primers corresponding to conserved sequences of the human growth factor-activatable NHE gene, RT-PCR revealed strong expression of NHE-1 mRNA in cerebral microvessels, choroid plexus, pial vessels and vascular smooth muscle cells relative to neocortical tissues from several species including rat, pig, cow, monkey and human subjects. Further confirmation of NHE-1 isoform mRNA expression in the cerebrovascular tissues was obtained by HpaII restriction digestion analysis and by subcloning and sequencing of the PCR amplified products. Our study suggests that mammalian cerebrovascular and choroidal tissues contain high amounts of the ubiquitous amiloride-sensitive [3H]MIA binding proteins consistent with the expression of NHE type 1 mRNA.

Amiloride↗

[Fundus flavimaculatus and choroidal neovascularization].

OBJECTIVE: Fundus flavimaculatus is an aspect of Stargardt disease, which is characterized by juvenile onset, rapidly progressive deterioration, and poor visual outcome due to atrophic areas or flecks. Recently, a late-onset form has been described, on the borderline with AMD. However, choroidal neovascular complications are not frequent and rarely described in Stargardt's disease. CASE REPORT: Late discovery of FFM in a patient over 50 years old. During her follow-up, she presented a decrease in visual acuity due to juxtafoveal choroidal neovascularization. In spite of laser treatment, a retrofoveal recurrence appeared, which was treated with perifoveal laser. DISCUSSION: Confusion between AMD and a late-onset Stargardt may occur because of their many clinical similarities. The population and the fundus results can be similar to AMD and an examiner may be confused. In the literature, choroidal neovascular complications appear in patients over 50 years of age who may suffer from AMD. In fundus flavimaculatus, pigmentary epithelium alterations are due to progressive lipoproteic scrap storage that predisposes to Bruch's membrane rupture and choroidal neovascularization. This physiopathology resembles the that of AMD. CONCLUSION: Choroidal neovascular complications are possible in late-onset Stargardt disease. Their appearance together may be greater than previously believed.

Choroidal Neovascularization↗

[Acute posterior multifocal placoid pigment epitheliopathy, serpiginous and multifocal choroiditis: etiological and therapeutic management].

PURPOSE: To highlight the importance of an extensive medical work-up in serpiginous and multifocal choroiditis, and acute posterior multifocal placoid pigment epitheliopathy before therapeutic management. PATIENTS AND METHODS: Records of patients referred to our department, between January 2000 and January 2002, for the diagnostic and therapeutic management of choroiditis or acute posterior multifocal placoid pigment epitheliopathy were retrospectively reviewed. All patients had a complete ophthalmologic examination, fluorescein and infrared angiographies. An extensive work-up was performed in order to exclude an infectious etiology. RESULTS: Fourteen patients were included (six cases of serpiginous choroiditis, four cases of multifocal choroiditis, and four cases of APMPPE). The mean age was 42.1 years and the sex ratio was 9: 5. Six patients presented with a history of tuberculosis in the family or with a tuberculosis primary infection. Toxoplasmic retinochoroiditis was confirmed in one case by a positive PCR applied to the aqueous humor. In the serpiginous choroiditis group, two patients have been treated with antituberculous drugs, one of whom was initially resistant to immunosuppressive regimens. In the acute posterior multifocal placoid pigment epitheliopathy group, one patient was treated with antituberculous drugs and another received antibiotics. CONCLUSION: An infectious agent may be associated with this group of clinical presentations. All patients presenting with severe forms of ocular inflammation, who resist to corticosteroids or immunosuppressive regimens, must undergo an extensive infectious work-up in order to propose a specific treatment.

Acute Disease↗

Adrenomedullin receptors in rat choroid plexus.

To characterize transmembrane signaling of adrenomedullin (AM) in the choroid plexus, we studied the effects of AM on cyclic AMP (cAMP) and cyclic GMP (cGMP) levels as well as expression of mRNA for AM receptor in the rat choroid plexus slices. AM or calcitonin gene-related peptide (CGRP) increased cAMP (but not cGMP) level in a concentration-dependent manner, with AM being much more potently than CGRP. AM mRNA as well as calcitonin-receptor-like receptor mRNA and receptor-activity-modifying protein 2 mRNA, were highly expressed in the choroid plexus. Our biochemical and pharmacological studies may raise the possibility that choroid plexus secretes AM into the cerebrospinal fluid, and AM regulates choroid plexus function in an autocrine/paracrine manner via acting on AM-specific receptors.

Adrenomedullin↗

Possible role of the choroid plexus in the supply of brain tissue with polyunsaturated fatty acids.

Delta-6 desaturase was measured in rat brain microvessels and choroid plexus by incubation in the presence of radioactive linoleic acid. Under our conditions, in 21-day-old animals, delta-6 desaturase was not detected in brain microvessels. In contrast, it was present in choroid plexus (about 21 pmol/min per mg protein). In comparison, the activity in brain was much lower (about 1 pmol/min per mg protein) and higher in liver (about 55 pmol/min per mg protein). Interestingly, during development the activity in choroid plexus peaked at day 6 after birth and declined slightly thereafter. The pattern of incorporation of linoleic acid radioactivity was not the same in choroid plexus and microvessels. These results show that delta-6 desaturase was not detected in brain microvessels but was present in choroid plexus.

Aging↗

[The choroid plexuses: a dynamic interface between the blood and the cerebrospinal fluid].

The choroid plexuses form one of the interfaces that control the brain microenvironment by regulating the exchanges between the blood and the central nervous system. They appear early during brain development. Originating from four different areas of the neural tube, they protrude into the ventricular system of the brain. The choroidal mechanisms involved in the control of brain homeostasis include the structural properties of the epithelial cells that restrict diffusional processes, as well as specific exchange and secretion mechanisms. In addition to the anatomical and histological organization of the choroidal tissue, this review describes the mechanism of cerebrospinal fluid secretion which is the most studied function of the choroid plexus. Experimental evidence for an implication of the choroid plexuses in neuroprotective mechanisms and in the supply of biologically active polypeptides to the brain are also reviewed.

Animals↗

Choroidal metastasis: case reports and review of the literature.

BACKGROUND: Choroidal metastases are recognized as the most common intraocular malignancy. Their diagnosis has become more common due to increased emphasis on comprehensive eye examinations for cancer patients and the improved life expectancy of patients with metastatic disease. They are most prevalent in female patients with breast cancer and male patients with lung cancer. METHODS: A thorough fundus examination, coupled with the use of A-scan and B-scan ultrasonography, will aid in their diagnosis. There are many ways of treating these tumors, including radiation therapy, chemotherapy, and monitoring. CASE REPORTS: Two case reports of patients diagnosed with choroidal metastases are discussed. Case 1 involved a patient with lung cancer who manifested a large bullous exudative retinal detachment due to an underlying choroidal metastasis. Case 2 dealt with treatment of a patient with metastatic transitional cell cancer who manifested a shallow exudative retinal detachment caused by a choroidal metastasis. CONCLUSIONS: Due to progress of chemotherapeutic medications, the number of patients who manifest choroidal metastases will continue to increase. It is essential for the practitioner to be able to recognize this disease process to prevent visual loss and institute referral for proper treatment for metastatic disease.

Aged↗

Central neural circuits for the light-mediated reflexive control of choroidal blood flow in the pigeon eye: a laser Doppler study.

Electrical stimulation in pigeons of the input from the medial subdivision of the nucleus of Edinger-Westphal (EWM) to the choroidal neurons of the ipsilateral ciliary ganglion, which themselves have input to the choroidal blood vessels of the ipsilateral eye, increases choroidal blood flow (ChBF). Since the EWM receives input from the contralateral suprachiasmatic nucleus (SCN), which in turn receives contralateral retinal input, the present study sought to determine if activation of the SCN by microstimulation or by retinal illumination of the contralateral eye would also yield increases in ChBF in that same eye. Using laser Doppler flowmetry (LDF) to measure ChBF, we found that electrical activation of the contralateral SCN by 100-Hz anodal pulse trains yielded increases in ChBF that were stimulus related and proportional to the stimulating current. These increases in ChBF elicited by the SCN stimulation were accompanied by increases in choroidal volume (vasodilation), but not by increases in systemic blood pressure. Furthermore, the increases could be blocked reversibly by lidocaine injection into the EWM. These results suggest that the increases in ChBF in the eye contralateral to the SCN stimulation were specifically mediated by the SCN-EWM pathway. Retinal illumination with a fiber optic light source was also found to increase ChBF in the illuminated eye, and these effects too could be blocked reversibly with lidocaine injection into the EWM or permanently by the EWM lesion. Control studies confirmed that the light-elicited increases were mediated by increases in choroidal volume (i.e. vasodilation), were not accompanied by systemic blood pressure increases, and were not artifactually generated by transocular illumination of the LDF probe. Thus, the SCN-EWM circuit may be involved in regulating ChBF in response to the level of retinal illumination and/or the visual patterns falling on the retina.

Analysis of Variance↗

Saturable transport of valproic acid in rat choroid plexus in vitro.

In order to obtain in vitro evidence for a specific transport system of valproic acid (VPA) at the blood-cerebrospinal fluid (CSF) interface, the uptake of VPA by isolated rat choroid plexus was investigated. The uptake clearance of [3H]VPA decreased with the increase of the unlabeled VPA concentration in the incubation medium. Kinetic analysis yielded an apparent Km of 10.0 mM, Vmax of 0.0871 mumol s-1 g-1 and Kns, a permeability coefficient of the nonsaturable component, of 6.85 microL s-1 g-1, indicating that both saturable and nonsaturable systems may contribute to VPA uptake by choroid plexus. Organic anions, penicillin G, p-aminohippurate, salicylate, and probenecid significantly inhibited VPA uptake by choroid plexus. We suggest that VPA translocation through choroidal membrane is partly operated by the organic anion transport system. A significant decrease of VPA uptake induced by 2,4-dinitrophenol, stilbenedisulfonate, and hypothermia (10 degrees C) indicates the involvement of an energy-dependent, carrier-mediated transport system. These results demonstrate that VPA is actively transported through the rat choroidal epithelium via a saturable system probably shared by organic anions.

4-Chloromercuribenzenesulfonate↗

PEPT2-mediated uptake of neuropeptides in rat choroid plexus.

PURPOSE: The peptide transporter PEPT2 was recently shown to be functionally active in rat choroid plexus, suggesting that it may play a role in neuropeptide homeostasis in the cerebrospinal fluid. This study, therefore, examined the role of PEPT2 in mediating neuropeptide uptake into choroid plexus. METHODS: Whole-tissue rat choroid plexus uptake studies were performed on GlySar in the absence and presence of neuropeptides and on carnosine. RESULTS: The neuropeptides NAAG, CysGly, GlyGln, kyotorphin, and carnosine inhibited the uptake of radiolabeled GlySar at 1.0 mM concentrations. In contrast, TRH, [D-Arg2]-kyotorphin, glutathione, and homocarnosine did not inhibit GlySar uptake. Kyotorphin, an analgesic, was a competitive inhibitor of GlySar with a Ki of 8.0 microM. The direct uptake of carnosine was also shown to be mediated by PEPT2 in isolated choroid plexus (Km = 39.3 microM; Vmax = 73.9 pmol/mg/min). Radiolabeled carnosine uptake was inhibited by 1.0 mM concentrations of GlySar or carnosine but not homocarnosine, L-histidine, or beta-alanine. CONCLUSIONS: These findings indicate that PEPT2 mediates the uptake of a diverse group of neuropeptides in choroid plexus, and suggests a role for PEPT2 in the regulation of neuropeptides, peptide fragments, and peptidomimetics in cerebrospinal fluid.

Animals↗

Retinal vascular alterations associated with dome-shaped and mushroom-shaped choroidal melanomas.

PURPOSE: Retinal vascular abnormalities are associated with choroidal melanoma. Although tumor ischemia, resulting in soluble angiogenic factor production, is a proposed etiology of these abnormalities, other sources of ischemia may also contribute. Mushroom-shaped choroidal melanomas have increased loss of the overlying choriocapillaris and increased subretinal fluid when compared to dome-shaped tumors; factors that may result in outer retinal ischemia, angiogenic factor production and resultant retinal vascular abnormalities. The differing amounts of retinal vascular abnormalities overlying dome-shaped compared to mushroom-shaped melanomas were determined to evaluate this hypothesis. METHODS: Retinal vascular abnormalities observed on fluorescein angiograms of eyes with choroidal melanoma were compared to the tumor configuration and presence of subretinal fluid. RESULTS: 23 eyes of 22 patients were included in the study. Retinal vascular abnormalities observed included dilated capillaries, telangiectatic capillaries, capillary nonperfusion, microaneurysms, neovascularization, lipid exudation and late staining of dye within the retina. Retinal vascular abnormalities were present in 4 of 14 eyes with dome-shaped tumors (29%) and in 8 of 9 eyes with mushroom-shaped tumors (89%). (Fisher's Exact Test, p = 0.009). Retinal vascular abnormalities were present in 2 of 10 eyes without subretinal fluid (20%) and in 10 of 13 eyes with subretinal fluid (77%). (Fisher's Exact Test, p = 0.012). CONCLUSIONS: Retinal vascular abnormalities are associated with mushroom-shaped choroidal melanomas more commonly than dome-shaped tumors. Outer retinal ischemia may result from choriocapillaris loss or the presence of subretinal fluid, contributing to soluble angiogenic factor production and resultant retinal vascular abnormalities in these eyes. SUMMARY STATEMENT: Retinal vascular abnormalities are associated with mushroom-shaped choroidal melanomas more commonly than dome-shaped tumors. These retinal vascular abnormalities may be related to an increase in outer retinal ischemia associated with mushroom-shaped tumors.

Adult↗

Distribution of the parathyroid hormone-related peptide and its receptor in the saccus vasculosus and choroid plexus in the red stingray (Dasyatis akajei: Elasmobranch).

1. The exact role of the parathyroid hormone-related peptide (PTHrP) is not fully understood. We used immunohistochemistry to localize the PTHrP and its receptor in the brain of the red stingray, particularly in the saccus vasculosus (SV) and choroid plexus. 2. Immunoreactive PTHrP and its receptor were detected in the epithelial cells of the SV and the choroid plexus. In addition, the neuronal perikarya in the nucleus of the SV located in the hypothalamus is positive for the PTHrP. 3. No PTHrP-containing neurons were detected in the choroid plexus. Extracts of SV and choroid plexus showed positive reactions against the PTHrP and its receptor antibody in Western blot analysis. 4. High levels of immunoreactive PTHrP were detected in the plasma equivalent to those present in human humoral malignant hypercalcemia. In contrast, the immunoreactive PTHrP concentration in the cerebrospinal fluid was below detectable levels. 5. Our results suggest that the regulation of the PTHrP in the SV differs from that in the choroid plexus in the red stingray.

Animals↗

Carcinoma of the ovary with primary presentation in the choroid.

PURPOSE: An unusual case of choroidal metastases from an ovarian adenocarcinoma is described, and a brief review of the literature is presented. METHODS: Clinical and autopsy findings are presented. RESULTS: After having diagnosed bilateral choroidal metastatic lesions, a clinical investigation and a subsequent laparotomy disclosed bilateral ovarian tumors with histopathological features of mucinous adenocarcinoma. At autopsy the tumor was confirmed to be a primary ovarian mucinous adenocarcinoma with choroidal metastases. CONCLUSION: This article describes what is believed to be the first case report of a primary epithelial carcinoma of the ovary with histopathologically documented metastases to the choroid. Metastatic disease must be considered in the evaluation of patients with choroidal lesions of unknown etiology.

Adenocarcinoma, Mucinous↗

Pulsatile flow in the choroidal circulation: a preliminary investigation.

A preliminary investigation has been made of choroidal blood flow using a computer-aided image analysis approach to interpretation of indocyanine green (ICG) dye choroidal angiograms. The goal of the study was to characterise blood flow through the choroidal arteries vs. choroidal capillaries and veins. The methods of analysis used are briefly reviewed, and preliminary data obtained mainly from monkey eyes are presented. Preliminary conclusions are made regarding the relationship between compliance of choroidal arterial vessels and blood flow through them.

Angiography↗