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Species differences in the distribution of gamma-glutamyl transpeptidase in choroid plexus of lateral ventricle and microvessels of adjacent brain.

The distribution of gamma-glutamyl transpeptidase in different vascular compartments of the central nervous system was evaluated in several common laboratory animals, i.e., hamster, gerbil, guinea pig, rat and mouse, by enzyme-histochemistry. Microvascular endothelium of the periventricular brain tissue stained positively in all five species. In contrast, the vascular endothelium of the choroid plexus stained positively only in the gerbil, and was negative in the other four species. Positive reactions for the transpeptidase was also found in choroid plexus epithelial cells in guinea pig, rat, and mouse; however no activity could be demonstrated in these cells of hamster and gerbil. The results demonstrate clear species differences in localization of the enzyme and suggest that gamma-glutamyl transpeptidase-promoted amino acid transport in choroid plexus is different in various animal species. It is also suggested that in gerbil, transpeptidase-aided amino acid transport takes place in endothelial cells of choroid plexus, whereas in guinea pig, rat and mouse this occurs in epithelial cells of choroid plexus. In the case of hamster, such aided transport is absent in endothelial as well as in epithelial cells of the choroid plexus. Thus, the hamster and the gerbil showed differences in gamma-glutamyl transpeptidase distribution, whereas the guinea pig, rat, and mouse showed similar enzyme distributions.

Animals↗

Indocyanine green angiography of choroidal tumors.

BACKGROUND: Fluorescein angiography (FA) has been widely used in the diagnostic evaluation of choroidal tumors. Indocyanine green angiography (ICG-A), which permits better visualization of choroidal vasculature than FA, has been recently introduced into clinical practice. Only few reports exist on the ICG-A characteristics of choroidal tumors. METHODS: The fluorescein and indocyanine green angiograms of 61 patients were assessed. These included 14 patients with choroidal nevi, 30 with malignant melanomas, 7 with suspected melanomas or atypical nevi, 5 with hemangiomas and 5 with metastases. RESULTS: The outline of pigmented tumors was more accurate on ICG-A than on FA. Characteristic patterns were seen in all intra-ocular tumors with ICG-A, so it was possible to distinguish hemangiomas from malignant lesions. Characteristic features of malignant melanomas include abnormal vascular pattern and marginal late dye leakage. None of the benign lesions showed these features. In suspected melanomas, the presence of abnormal choroidal vascular patterns and/or late dye leakage on ICG-A may indicate malignancy. CONCLUSION: The study suggests that ICG-A can yield additional information that is useful in differentiating amongst choroidal tumors. Better delineation of pigmented lesions with ICG-A allows more accurate treatment planning and follow-up.

Choroid Neoplasms↗

Nitrergic and VIPergic neurons in the choroid and ciliary ganglion of the duck Anis carina.

Immunohistochemistry for neuronal nitric oxide synthase (nNOS) and vasoactive intestinal peptide (VIP), and NADPH diaphorase histochemistry, were applied to investigate neurons in the choroid and the ciliary ganglion of the muscovy duck Anis carina. Up to 1000 neurons in the choroid stained for NADPH diaphorase and showed virtually complete colocalization for nNOS immunoreactivity. Almost all of them co-stained for VIP, while about 90% of VIP immunoreactive cell bodies showed colocalization for nNOS. Two-thirds of the neurons were located, mostly singly, at nodes of a wide-meshed nerve plexus in the suprachoroid and were only rarely grouped in ganglia of up to 3 neurons. Numerous varicose nNOS/NADPH-diaphorase-positive nerve fibers were seen around large arterial blood vessels. These fibers derived mainly from paravascular cell bodies that represented about one-third of all choroidal neurons and also displayed costaining for nitrergic markers and VIP. Colocalization of nNOS/NADPH-d and VIP could be demonstrated in most of the perivascular fibers, while slightly more VIP-positive axons in the suprachoroid plexus did not costain for nNOS/NADPH-d. Small-caliber blood vessels and those localized in the choriocapillaris were not endowed with VIP/nNOS/NADPH-diaphorase-positive fibers. A few reactive neuronal cell bodies were also found in ciliary nerves, while most ciliary axons were unstained. In the ciliary ganglion a small subpopulation of neurons showed VIP/nNOS/NADPH-diaphorase colocalization. There were also nNOS/NADPH-d-positive cap-like terminals on ciliary ganglion cells. The presence of VIP/nNOS/NADPH-diaphorase positive neurons and nerve fibers in both the choroid and ciliary ganglion, and in the choroidal perivascular plexus, indicates peripheral nitrergic and VIPergic control of blood flow in the choroid of the duck.

Animals↗

Serotonergic effects on carbonic anhydrase activity in the choroid plexus.

The carbonic anhydrase (CA) activities in the choroid plexus of dogs were investigated by electron microscopy, and the effects of 5-hydroxytryptophan (5-HTP) on them were examined to elucidate the participation of serotonin in the production of cerebrospinal fluid. The reaction products yielded by the method employed proved to be CA activity by elimination tests using acetazolamide (Diamox). Following administration of 5-HTP, the CA activities fell to 43.3% of the control value, that is, approximately 56% of the CA activities in the choroid plexus were affected by serotonin. When tetrabenazine (TBZ) was administered, the CA activities in the choroid plexus decreased to 22.4% of the control value. These results suggest that the CA activity in the choroid plexus is remarkably suppressed when nervous control of the choroid plexus is disturbed by the administration of a monoamine denervator such as TBZ. The present data indicate that the serotonergic inhibitory effect on the CA activity in the choroid plexus may be less predominant than that of TBZ and acetazolamide.

5-Hydroxytryptophan↗

Clinicopathologic correlations in epithelial choroid plexus neoplasms: a study of 52 cases.

Sixty-seven tumor specimens of epithelial choroid plexus neoplasms obtained by 60 biopsies and 7 autopsies from 52 patients were investigated. Diagnoses of the first operations were choroid plexus papilloma (PP; 32 cases), choroid plexus papilloma with histological atypies (atypical PP; 6 cases), and choroid plexus carcinoma (PC; 14 cases). Carcinoembryonic antigen was expressed by 2 of the 3 biopsies autoptically recognized as metastatic carcinomas and by 2 autopsy cases of PC, while it was absent in all biopsies of true choroid plexus tumors. Tumor cells positive for transthyretin (TTR, prealbumin), S-100 protein (S100), and glial fibrillary acidic protein (GFAP) were detected in 39, 46 and 13, respectively, of the 49 cases of true choroid plexus tumors. Fourth ventricle tumors expressed more S100 (number of positive tumor cells) than lateral ventricle tumors, PP more S100 and TTR than atypical PP/PC. Tumors from patients 20 years of age and older expressed more GFAP and TTR than tumors from younger patients. Of the 30 patients with complete follow-up 19 were alive 2 to 11 years after surgery, including 7 recurrencies. Eleven died from the tumor 4 months to 7 years after surgery. The following histopathologic features (in order of decreasing significance) were correlated with poor prognosis (recurrency or fatal outcome): less than 50% of the tumor cells heavily positive for S100, presence of mitoses, absence of TTR-positive cells, brain invasion by cell nests, absence of marked stromal edema, and presence of necrotic areas. Our results indicate that some histologic features correlate significantly with poor prognosis and that immunohistochemical results correlate with tumor localization, age, and malignancy.

Adolescent↗

CT of malignant choroidal melanoma - morphology and perfusion characteristics.

The computed tomographic morphology of malignant choroidal melanoma and its perfusion characteristics are described. Thirty-three static and serial CT examinations made on 29 patients with choroidal melanoma, three with pseudotumors of the macula and one with choroidal metastasis revealed the choroidal melanoma to be usually a hyperdense, markedly perfused tumor, while the non-contrast diagnostically undifferentiable pseudotumors and the choroidal metastasis, revealed no significant change in density after the administration of contrast material. Density values of perfusion characteristics of choroidal melanoma that are outside of the normal range are a result of secondary changes within the immediate surroundings of the tumor, such as detachment of the retina, tumor-induced glaucoma, or tumor necrosis.

Adult↗

The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid.

BACKGROUND: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating keratoplasty (PKP) and following treatment with cyclosporin A (CsA). METHODS: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n = 24); (ii) operated, CsA-treated (10 mg/kg i.m.; n = 22). Controls were groups (iii) normal LW rats (n = 13); (iv) unoperated, CsA-treated (16 days' treatment; n = 8); (v) anterior perforation of the anterior chamber (n = 3); (vi) eight corneal sutures only (n = 4); (vii) syngeneic operated (LW to LW; n = 4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. RESULTS: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. CONCLUSION: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.

Animals↗

Isolation of visna-maedi virus from the choroid plexus of an apparently healthy sheep in Italy.

In this paper, the presence of visna-maedi in Italy, reported to exist since 1982 on clinical grounds, and the presence of anti-visna-maedi antibody is confirmed by the isolation of the viral agent from choroid plexus cells of an apparently healthy sheep. Gel diffusion test antigen, prepared from the explanted choroid plexus cells and from normal choroid plexus cells infected with the isolated agent, gave a positive reaction with one or two identity lines with reference antigens. The isolated agent gave both a characteristic cytopathic effect and a cytoplasmic fluorescence starting 24 hours after infection in normal choroid plexus cell cultures. Fluorescence was observed neither in control normal choroid plexus cells nor in infected normal choroid plexus cells incubated with a visna-maedi negative serum. By electron microscopy, budding forms arising from the cell membrane and extracellular particles of two distinct types were observed. One type was characterized by an electron-dense central core and a single membrane, and ranged from 80 to 110 nm, while the other had elongated bar-like cores and a double wall, and ranged from 100 to 140 nm. The characteristics observed for the isolated agent are identical to those reported by various authors for visna-maedi virus.

Animals↗

Tubular (acinar) transformation of the choroid plexus epithelium.

The choroid plexus in the normal state shows a beautiful papillary (or villous) architecture supported by the intricately ramifying, thin fibrovascular stroma. This configuration is retained in benign and malignant neoplasms derived therefrom. The choroid plexus was involved in the pathological process of leukemic cell infiltration in one case reported here and in chronic cryptococcal leptomeningitis in the other case. The epithelial cells of the choroid plexus of the lateral ventricle were arranged extensively in a tubular (acinar) configuration, in association with remarkable stromal fibrosis caused by an infiltration of leukemic or inflammatory cells. In addition, choroid plexus epithelial cells in the first case contained a moderate amount of intracytoplasmic glycogen. These two cases indicate that the non-neoplastic choroid plexus epithelium can undergo transformation into a tubular (acinar) structure as a response or adaptation to the fibrotic processes of the stroma. This finding should be differentiated from metastatic adenocarcinoma. This finding also provides some suggestions as to the pathogenesis of "tubular (acinar) adenoma," a rare variant of benign choroid plexus neoplasm.

Arachnoid↗

[Morphologic classification of choroidal invasion of retinoblastoma].

In order to inquire into standard for morphologic classification of choroidal invasion of retinoblastoma and to study the tumor clinic--pathologic further under the integrated scale, the changes of retinal pigment epithelium, Bruch's membrane and choroid on the histopathological sectins of 297 cases of primary enucleated eyes of retinoblastoma were retrospectively observed under the light microscopy. The choroidal invasion was morphologically divided into four stages: Stage 1, only retinal pigment epithelium involved, the Bruch's membrane was intact; Stage 2, the Bruch's membrane was destroyed and the choroidal capillaris was not infiltrated; Stage 3, choroial capillary and middle blood vessel layer in small limits were infiltrated; Stage 4, invasion involved in choroid in great limits and involvement of sclera existed simultaneously. This classification (also called pigment epithel--choroid stage, PEC--stage) reflected both infiltrated procedure of tumor cells and preventive mechanism in eye and morphological criterion half--quantitatively. It can be used as a united standard to compare the infiltration degree of retinoblastoma among different individuals and different studies.

Adolescent↗

Mitochondrial content of choroid plexus epithelium.

The objective of the present study was to examine the apparent work capacity of one of the two separate membrane systems (the blood-cerebrospinal fluid barrier) that isolate the mammalian brain extracellular fluid (and cerebrospinal fluid, CSF) from plasma. Digitized analyses of electron-microscopic images provided estimates of mitochondrial volumes, which were expressed as a percentage of the cell cytoplasm. We recorded a high mitochondrial content of 12-15% in the cuboidal epithelium of primate choroid plexus, which was consistent in vervet, rhesus, and squirrel monkeys, as well as in baboons. Similarly high mitochondrial contents were observed in the rabbit, rat, and mouse choroid plexus. It has been postulated that the high mitochondrial content of brain endothelium is associated with maintaining the ionic gradients within the central nervous system. We observed that the mitochondrial content of the choroid plexus (where CSF is produced) was slightly higher than in (prior measurements of) the blood-brain barrier (BBB). In addition, surface areas at the apical borders of the choroid plexus epithelia (where the Na+K+ATPase activity has been localized) were increased 7- to 13-fold over the basal borders, in the primate species examined. The observation of high mitochondrial volumes in choroid plexus cells is consistent with the suggestion that increased mitochondrial densities seen in choroidal epithelia and BBB capillaries provide a metabolic work capability for both secretory activities and maintaining ionic gradients across blood-CSF barriers.

Animals↗

Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in children?

Hydrocephalus is a common neurological disorder in children and the result of a variety of causes. However, with the advancement of imaging modalities, particularly MRI, previously reported rarer causes of hydrocephalus in children are now being more readily appreciated. We report an 11-year-old boy with diffuse villous hyperplasia of the choroid plexus. He had a ventriculo-peritoneal (VP) shunt in-situ and a prior diagnosis from infancy of congenital aqueduct stenosis as the cause of his hydrocephalus. His current presentation was with further shunt dysfunction. CT and MRI demonstrated enlarged choroid plexuses but did not confirm aqueduct stenosis. CSF overproduction was demonstrated from the externalized ventricular drain. The enlarged choroid plexuses were surgically resected and histology confirmed choroid plexus hyperplasia. Identification of choroid plexus hyperplasia is important since the neurosurgical management of hydrocephalus is not VP shunt insertion, but resection of the hyperplastic choroid plexus.

Cerebral Aqueduct↗

[Changes in neovascular membranes and normal choroid blood vessels after multiple photodynamic therapy treatments].

PURPOSE: ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid. METHODS: Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA). RESULTS: A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment. CONCLUSION: The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.

Capillary Permeability↗

Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas.

CASE REPORT: A 10-month-old boy, with congenital deafness and blindness associated with chromosomal deletion [46XY, del(13)(q32)], presented with intractable ascites 9 months after ventriculo-peritoneal shunting for congenital hydrocephalus. Revision of the ventriculo-atrial shunt resulted in shunt failure 1 month later. External ventricular drainage revealed cerebrospinal fluid (CSF) overproduction (2,000 ml/day). Magnetic resonance imaging showed marked lobular enlargement of the bilateral choroid plexuses extending from the trigone to the body and inferior horn of the lateral ventricle. Multi-staged resection was performed via bilateral temporo-occipital transcortical approaches, and CSF production significantly decreased to 100 ml/day postoperatively. Histological assessment of the villous surface suggested villous hyperplasia of the choroid plexus and thorough evaluation including the proximal portion of the lobular lesion near the attachment revealed choroid plexus papilloma. He was discharged after ventriculo-peritoneal shunting without additional neurological deficits except for hyperreflexia of the left extremities. CONCLUSION: CSF overproduction caused by bilateral choroid plexus papillomas can result in hydrocephalus. Radical resection of the bilateral ventricular lesions should be considered for this entity. Thorough evaluation of the surgical specimen is recommended because histological examination of only the lobular surface of the choroid plexus lesion may fail to identify choroid plexus neoplasm.

Cerebrospinal Fluid↗

Indocyanine green angiographic findings in diffuse choroidal hemangioma associated with Sturge-Weber syndrome.

PURPOSE: To analyze indocyanine green angiography (ICGA) features in one case of diffuse choroidal hemangioma associated with Sturge-Weber syndrome. METHODS: Color fundus photography, fluorescein angiography (FA) and ICGA were performed in a patient with diffuse choroidal hemangioma associated with Sturge-Weber syndrome. RESULTS: The diffuse choroidal hemangioma was not identified by FA. ICGA revealed that the vascular tissue of the diffuse hemangioma filled rapidly with dye during the arterial phase of the choroidal angiogram; copious dye leakage appeared early and persisted into the late phase of angiography. Late "wash-out" phenomenon was not observed 30 minutes after dye injection. Sectors of reduced choroidal perfusion in the upper or lower half of the midperiphery were present. CONCLUSION: ICGA may be an important and sensitive technique in detecting the diffuse choroidal hemangioma associated with Sturge-Weber syndrome.

Adolescent↗

Clinicopathological correlation in exudative age-related macular degeneration: recurrent choroidal neovascularization.

PURPOSE: To report the pathology of surgically removed submacular tissue in recurrent choroidal neovascularization after laser photocoagulation of classic choroidal neovascularization in age-related macular degeneration. METHODS: A recurrent subfoveal choroidal neovascular membrane was surgically removed in two patients. The recurrence was identified as a classic membrane on fluorescein angiography at the foveal border of the laser scar. A net was visualized in the early venous phase of the indocyanine green angiogram, with associated late hyperfluorescence. Both patients had undergone laser photocoagulation for a classic interpapillomacular choroidal neovascular membrane about 1 1/2 years earlier. The specimens were serially sectioned and stained with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome and phosphotungstic acid-hematoxylin. RESULTS: The two specimens consisted of subretinal fibrovascular tissue with fibrin exudation. Fibrovascular tissue bordered subretinal fibrous tissue adherent to Bruch's membrane and remnants of the choroid in one patient. The fibrovascular portion most likely corresponded to the recurrence, whereas the fibrous portion represented the original membrane, being obliterated after photocoagulation. Some peripapillary tissue was additionally removed in the other patient. The latter lesion was invisible on fluorescein angiography but stained in the late phase of indocyanine green angiography and corresponded histopathologically to poorly vascularized intra-Bruch's fibrovascular tissue. Granular deposits, periodic acid-Schiff positive and metachromatically purple on Masson trichrome stain, representing diffuse drusen (basal laminar/linear deposits), were identified in the three specimens. CONCLUSION: A subretinal fibrovascular membrane corresponded with the classic recurrent choroidal neovascularization.

Aged↗

Primary vitrectomy for the management of rhegmatogenous retinal detachment associated with choroidal detachment.

PURPOSE: To evaluate the role and the results of primary vitrectomy in treating cases with coexisting rhegmatogenous retinal detachment and choroidal detachment. METHODS: Eleven consecutive eyes with coexisting rhegmatogenous retinal detachment and choroidal detachment with proliferative vitreoretinopathy less than grade C were included. Release of traction on the breaks was achieved by vitrectomy and augmented by episcleral buckle if needed. Perfluorocarbon liquids were used to drain the subretinal fluid through the vitrectomy sclerotomies. The breaks were treated by endolaser under perfluorocarbon liquids. Postoperative tamponade was done by C3F8 gas or silicone oil. Cases were followed up for at least 3 months. RESULTS: Retinal reattachment could be achieved and maintained in all cases by one or more surgeries. No recurrence of choroidal detachment has occurred. In each case, choroidal detachment was drained through the sclerotomies and retinal detachment was repaired. CONCLUSION: Primary vitrectomy represents an effective line in the management of rhegmatogenous retinal detachment with coexisting choroidal detachment in phakic or nonphakic eyes. SUMMARY: Primary vitrectomy is recommended for the management of choroidal detachment associated with retinal detachment.

Aged↗

Asymmetric localization of Notch2 on the microvillous surface in choroid plexus epithelial cells.

Notch family molecules are transmembrane receptors that play various roles in contact-dependent cell-cell interactions in a wide range of organs. In the brain, Notch2, but not the other members of Notch, is expressed in the choroid plexus at an exceptionally high level. We immunohistochemically examined the cellular and subcellular localization of Notch2 protein in the choroid plexus using confocal and electron microscopy. Unexpectedly, Notch2 was asymmetrically localized on the microvillous surface of epithelial cells in the choroid plexus of both postnatal and adult rats. This localization pattern of Notch2 suggests its novel and unknown role independent of contact with adjacent cells in the choroid plexus. In organotypic cultures of the choroid plexus, the addition of anti-Notch2 antibody resulted in deformation of microvilli in epithelial cells, which suggests a role of Notch2 in the maintenance of the microvillous structure in choroid plexus epithelial cells.

Animals↗