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Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid.

Polymorphisms in the complement factor H gene (CFH) are associated with a significantly increased risk for, or protection against, the development of age-related macular degeneration (AMD). The most documented risk-conferring single-nucleotide polymorphism results in a tyrosine-to-histidine substitution at position 402 (Y402H) of the CFH protein. In this work, we examined the ocular distributions and relative abundance of CFH, several CFH-binding proteins, and abundant serum proteins in the retinal pigmented epithelium (RPE), Bruch's membrane, and choroid (RPE-choroid) in CFH homozygotes possessing either the "at-risk" 402HH or "normal" 402YY variants. Although CFH immunoreactivity is high in the choroid and in drusen, no differences in CFH-labeling patterns between genotypes are apparent. In contrast, at-risk individuals have significantly higher levels of the CFH-binding protein, C-reactive protein (CRP), in the choroidal stroma. Immunoblots confirm that at-risk individuals have approximately 2.5-fold higher levels of CRP in the RPE-choroid; no significant differences in the levels of CFH or other serum proteins are detected. Similarly, we find no differences in CFH transcription levels in the RPE-choroid nor evidence for local ocular CRP transcription. Increased levels of CRP in the choroid may reflect a state of chronic inflammation that is a by-product of attenuated CFH complement-inhibitory activity in those who possess the CFH at-risk allele. Because the CRP-binding site in CFH lies within the domain containing the Y402H polymorphism, it is also possible that the AMD risk-conferring allele alters the binding properties of CFH, thereby leading to choroidal CRP deposition, contributing to AMD pathogenesis.

Age Distribution↗

Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system.

PURPOSE: The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method. METHODS: The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically. RESULTS: Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed. CONCLUSIONS: Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy.

Animals↗

Identification of choroidal ovotransferrin as a potential ocular growth regulator.

PURPOSE: In an effort to identify choroidal factors potentially involved in the regulation of ocular growth, proteins released into culture medium of organ-cultured choroids were compared between control eyes and eyes recovering from form deprivation myopia. METHODS: The choroids were obtained from the posterior poles of control and recovering chick eyes, and placed into organ culture containing ( 35)S-methionine/(35)S-cysteine. Culture medium was collected after 24 hours and proteins were separated and identified by SDS-polyacrylamide gel electrophoresis (SDS-PAGE), fluorography, immunoprecipitation, western blot analysis and by amino acid sequencing. Choroidal proteins were tested for their effect on scleral proteoglycan synthesis by measuring (35)SO( 4) incorporation into scleral glycosaminoglycans (GAG) in vitro. Choroidal thickness and axial elongation were measured in control and recovering eyes using high frequency A-scan ultrasound. RESULTS: The synthesis of an 80 kD protein was greatly increased in the choroids of recovering eyes compared with those of control eyes. Amino acid sequencing and immunoprecipitation indicated that the newly synthesized 80 kD protein was ovotransferrin (transferrin, conalbumin). Ovotransferrin release into the culture medium by isolated recovering choroids was associated with a decrease in the rate of axial elongation in recovering eyes. When tested in vitro, ovotransferrin (500 ng/micro) inhibited scleral proteoglycan synthesis in the sclera by 62% in a dose-dependent manner. CONCLUSIONS: Chick choroids of recovering eyes synthesize and release ovotransferrin during the recovery from form deprivation myopia. Ovotransferrin significantly inhibited proteoglycan synthesis by the sclera, indicating that ovotransferrin may play a role in slowing the rate of vitreous chamber elongation and facilitating the recovery from induced myopia.

Amino Acid Sequence↗

Infection of the choroid plexus by feline immunodeficiency virus.

The human, simian, and feline immunodeficiency viruses rapidly penetrate into the brain and trigger an inflammatory process that can lead to significant neurologic disease. However, the mechanisms that permit efficient trafficking of macrophage-tropic and the more neurotoxic lymphocytotropic isolates are still poorly understood. One potential source of virus entry may be the blood-CSF barrier provided by the choroid plexus. Infected cells are often detected within the choroid plexus but it is unclear whether this reflects trafficking cells or infection of the large macrophage population within the choroidal stroma. To address this issue, we cultured fetal feline choroid plexus and evaluated the ability of feline immunodeficiency virus (FIV) to establish a primary infection. Significant provirus was detected in macrophage-enriched choroid plexus cultures as well as in the choroid plexus of cats infected in vivo. FIV p24 antigen production in vitro was very low but detectable. Addition of a feline T-cell line to macrophages inoculated with FIV resulted in a dense clustering of the T cells over macrophages with dendritic cell-like morphologies and a robust productive infection. The direct infection of choroid plexus macrophages with FIV, the efficient transfer of the infection to T cells indicate that the choroid plexus can be a highly efficient site of viral infection and perhaps trafficking of both macrophage-tropic and T-cell-tropic viruses into the CNS.

Animals↗

Comparison of refractive state and circumferential morphology of retina, choroid, and sclera in chick models of experimentally induced ametropia.

PURPOSE: Simultaneous comparisons of the circumferential morphological tissue profiles and final refractions from form-deprivation myopia (FDM), defocus-induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia have been made to test the hypothesis that changes in the thickness profiles of the three coats of the eye, and particularly that of the choroid, can be predicted from the degree of induced refractive error. METHODS: Hatchling chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were refracted using retinoscopy and were then sacrificed, and whole eyes were processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous sclera (CS) thickness measurements were made from photographic collages of the entire circumference of the globe. Of the 23 chickens, complete morphological profile data were available for both eyes of 10 animals (nine treated and one normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens were used as experimental controls as paired comparisons for statistical analyses. RESULTS: Morphological profiles of control and experimental eyes revealed significant systematic regional variations in tissue thickness. This variation was related to nasal or temporal eccentricity with the nasal side generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM and DIM eyes showed very similar anatomical responses despite significantly different degrees of refractive change. DIH eyes showed significant increases in choroidal thickness but none in retinal or CS thickness. Analysis of fellow control eyes indicated that in both myopia models (FDM and DIM), significant changes in all tissues of the untreated fellow eyes occur whereas only the choroid of the fellow eye was affected in the hyperopic (DIH) model. CONCLUSIONS: The morphological similarity observed in the circumferential profiles of the retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite approximately 20 D difference in final refraction suggests that choroidal thickness is not a good predictor of final refractive error across models. Similarly, the final refractive difference of approximately 20 D between the DIM and the DIH eyes did not receive a major contribution from the final difference in choroidal thickness (with its implied effect on vitreous chamber length).

Animals↗

Laser photocoagulation of choroidal neovascularization in angioid streaks.

PURPOSE: To determine if laser photocoagulation of macular choroidal neovascularization in angioid streaks may be effective in preventing severe loss of vision. METHODS: Sixty-six consecutive eyes of 52 patients with extrafoveal, well-defined choroidal neovascularization secondary to angioid streaks who underwent direct laser photocoagulation were followed for 3-108 months (mean, 34.5 months; median, 20 months). RESULTS: Pretreatment mean visual acuity was 20/40 (range, 20/200-20/20), postlaser outcome was a visual acuity of 20/50 at 3 months, 20/50 at 6 months, 20/80 at 1 year, 20/80 at 2 years, 20/100 at 3 years, 20/125 at 4 years, 20/125 at 5 years, 20/100 at 6 years, and 20/80 at 7 years. During the first year after treatment there was a significant decrease in visual acuity (P < 0.01), but no significant change thereafter. Choroidal neovascularization recurred one or more times in 77% of the eyes, but by the final examination choroidal neovascularization had been eliminated completely in 31 eyes (47%). Fellow eyes with naturally progressed choroidal neovascularization were considered control eyes. Final visual acuity in treated eyes was definitely better than that in untreated eyes (P < 0.01). CONCLUSIONS: This is the largest series of eyes treated by laser photocoagulation for angioid streaks and choroidal neovascularization ever reported. Laser photocoagulation of choroidal neovascularization in angioid streaks may end the choroidal neovascularization and help stabilize visual acuity or slow down visual loss. Considering the very high frequency of recurrences (77% of the eyes studied), an intense clinical and fluorangiographic follow-up period is strongly recommended, mainly for the first 3 months after treatment.

Adult↗

Confluent choroidal infiltrates with sarcoidosis.

PURPOSE: To report the occurrence of confluent plaquelike choroidal infiltrates in four patients with sarcoidosis. METHODS: The medical records of patients with choroidal plaquelike infiltrates and presumed systemic sarcoidosis seen in the Mayo Clinic were reviewed. RESULTS: The cohort included four patients with confluent plaquelike choroidal infiltrates and systemic sarcoidosis. The most common ophthalmic symptom experienced by the patients was mild blurring of vision. The salient ophthalmic findings were choroidal infiltrates generally unaccompanied by other features frequently seen with sarcoidosis such as periphlebitis, multiple small yellowish choroidal infiltrations, vitreous cellular reaction, and granulomatous anterior uveitis. The choroidal lesions were confluent, yellowish, irregularly thickened infiltrates that frequently radiated peripherally from a peripapillary location in an ameboidlike pattern. Fluorescein angiography demonstrated early hypofluorescence and progressive patchy hyperfluorescence with late staining of the active lesions. Treatment with either systemic or subconjunctival steroids was associated with improvement in vision and partial resolution of the choroidal lesions. In two patients some of the lesions resolved spontaneously and became replaced by areas of chorioretinal atrophy. CONCLUSION: Plaquelike yellowish choroidal infiltrates associated with systemic sarcoidosis may occur in eyes remarkably free of other signs of inflammation. The infiltrates tend to radiate from the region of the optic nerve in a confluent ameboidlike pattern. They generally respond to corticosteroids and may be the first recognized manifestation of systemic sarcoidosis.

Adrenal Cortex Hormones↗

Aging changes of the choroidal dye filling pattern in indocyanine green angiography of normal subjects.

PURPOSE: To study the aging changes in the choroid of healthy volunteers with indocyanine green (ICG) angiography. METHODS: Video ICG angiography with adjunctive computer-assisted image analysis was performed on 35 eyes of 30 healthy volunteers (age range, 21-81 years; mean +/- standard deviation, 50.5 +/- 16.2 years) to observe the aging changes of the choroid. RESULTS: In patients in the second and third decades of life, the subfoveal choroidal arterioles fluoresced initially with subsequent rapid filling of the feeding arterioles and choriocapillaris. The watershed zone was clearly observed. In patients older than age 50, the choroidal vasculature filled more slowly. Eventually, the margin of the watershed zone became blurred. The quantitative analysis showed that the number of choroidal arterioles and the fluorescent intensity in the macular region were reduced with age (P < 0.005). In the early venous phase, hypofluorescent patches seen in all ages increased in size and number and remained with aging. The mean fluorescence intensity was not correlated statistically with age. CONCLUSIONS: The features of normal aging patterns of the choroid that we investigated are essential to the interpretation of ICG angiography and may help in understanding the physiologic and pathologic conditions of the choroidal circulations and the choroid and retina themselves.

Adult↗

Ultrasonography of metastases and melanomas of the choroid.

Choroidal metastases and melanomas are the most common intraocular neoplasms. Choroidal metastases may appear clinically similar to other amelanotic tumors, and the diagnosis may be difficult in the absence of a history of extraocular malignancy. Ultrasonography, using A- and B-mode criteria, offers an opportunity for high accuracy in the diagnosis of choroidal tumors. However, a considerable overlapping of ultrasonographic parameters, such as tumor solidity, vascularity, and choroidal excavation, has been demonstrated for choroidal melanomas and metastases. We have found that choroidal metastases are characterized by a significantly lower height-to-base ratio than melanomas, whereas reflectivity is significantly higher in metastases. Thus the combined use of height-to-base ratio and reflectivity provides a highly significant differentiation between choroidal melanomas and metastases. This observation has further improved the diagnostic value of ultrasonography in the differentiation of choroidal tumors.

Choroid Neoplasms↗

Autocrine role of insulin-like growth factor II secretion by the rat choroid plexus.

Insulin-like growth factor II (IGF-II) is expressed and secreted by the choroid plexus and has been suggested to act as a trophic factor in the adult mammalian central nervous system. The aim of the present study was to investigate whether IGF-II has an autocrine role in the choroid plexus. Using in situ hybridization we demonstrate that IGF-II is primarily expressed in the epithelium of adult rat choroid plexus. Conditioned medium from primary cultures of purified rat choroid plexus epithelial cells, intact choroid plexus tissue, as well as rat CSF, displaced IGF-II binding to a 23 HMM melanoma cell line in an IGF-II radioreceptor assay. The presence of IGF-II and IGF binding protein-2 in conditioned medium was shown by Western immunoblot. The mitotic activity in choroid plexus epithelial cell cultures was quantified by immunohistochemical staining of bromodeoxyuridine incorporated into cell nuclei. A monoclonal antibody towards IGF-II inhibited cell division by 35%, while IGF-I increased the number of stained nuclei by 75%. Basic fibroblast growth factor stimulated cell division at low concentrations, but had no effect at high concentrations. Growth hormone had no effect. We conclude that IGF-II in the choroid plexus could have an autocrine role in the regulation of choroid plexus epithelial cell growth.

Animals↗

Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats.

The aim of this study was to quantitatively determine the constitutive expression levels of various transporter mRNAs in rat choroid plexus. To provide a reference for the relative expression levels, the expression of various transporter mRNAs in choroid plexus were compared with that in liver, kidney, and ileum. The mRNA levels of multidrug resistance protein (Mrp)1, 2, 3, 4, 5, and 6; multidrug resistance (Mdr)1a, 1b, and 2; organic anion transporting polypeptide (Oatp)1, 2, 3, 4, 5, 9, 12, and Oat-K (1/2); organic anion transporter (Oat)1, 2, and 3; organic cation transporter (Oct)1, 2, 3, N1, and N2; bile acid transporters sodium taurocholate cotransporting polypeptide (Ntcp), bile salt excretory protein (Bsep), and ileal bile acid transporter (Ibat); divalent metal transporter 1 (DMT1), Menke's and Wilson's metal transporters; equilibrative nucleotide transporters (Ent) 1 and 2, and constitutive nucleotide transporters (Cnt)1 and 2; peptide transporters (Pept)1 and 2; as well as ATP-binding cassette (Abc)G5 and 8 were measured in choroid plexus by the branched DNA signal amplification method. Mrp1, 4, and 5, Oatp3, Menke's transporter, DMT1, Ent1, and Pept2 mRNAs were expressed in choroid plexus at higher levels than in liver, kidney, or ileum. OctN1 and N2, Oatp2, Oat2 and 3, and Cnt1 and 2 mRNAs expressions were detectable in choroid plexus, but the levels were lower compared with that in liver, kidney, or ileum. The remaining transporters [Mrp2, Mrp3, Oct1, Oct2, Oatp1, Oatp4, Oatp5, Oatp12, Oat-K (1/2), Ntcp, Bsep, Ibat, Mdr1a, Mdr1b, Mdr2, Oat1, Ent2, Pept1, AbcG5, AbcG8] were expressed at very low levels in choroid plexus. The constitutive expression levels of different transporters in choroid plexus may provide an insight into the range of xenobiotics that can potentially be transported by the choroid plexus, thereby providing a means of xenobiotic detoxification in the brain.

Animals↗

Automated perimetry in patients with choroidal metastases.

AIMS/BACKGROUND: Recent work using computerised perimetry has documented predictable visual field defects in patients with choroidal melanoma. Despite the higher frequency of occurrence of choroidal metastases, relatively little is known about their exact effects on visual performance, specifically with respect to visual field. This study is a pilot retrospective analysis of the results of automated perimetry testing in patients with choroidal metastatic disease. METHODS: The Humphrey field analyser was used to perform visual field tests on 15 eyes in 11 patients diagnosed with choroidal metastases. All 11 primary tumours were carcinomas originating in the breast (seven), lung (one), kidney (one), stomach (one), and prostate (one). All patients had either central 30 and/or peripheral 30-60 threshold strategies. RESULTS: Each of the 15 eyes tested had a demonstrable visual field defect. Eight eyes (53%) had absolute scotomas and seven (43%) had relative scotomas; the defects did not consistently correspond in size or location to the tumour as depicted by ophthalmoscopy or ultrasonography. This is in contradistinction to automated perimetry results in patients with choroidal melanoma. Three of the four eyes (75%) which were retested after treatment of the metastases showed improvement of the visual field. Seven of nine eyes (77%) that initially had reduced visual acuity had improvement after treatment. This clinical improvement corresponded well to tumour shrinkage and resolution of subretinal fluid. CONCLUSION: These findings may be useful in the decision to initiate treatment for symptomatic choroidal metastatic disease and in explaining to patients and their referring physicians what improvement could be expected from such treatment. A prospective evaluation of patients with choroidal metastases seems appropriate based on this pilot experience and may elucidate if the differences noted between visual field performance of these patients and those with choroidal melanoma may be useful in some diagnostically difficult cases.

Adult↗

Macrophages and MHC class II positive cells in the choroid during endotoxin induced uveitis.

AIMS/BACKGROUND: Endotoxin induced uveitis has been regarded as a model for acute anterior uveitis and until now little was known about choroidal involvement. The aim of this study was to investigate changes in macrophages and MHC class II positive cells in the choroid of Lewis rats during endotoxin induced uveitis. METHODS: Choroid-sclera wholemounts were isolated from normal Lewis rats and at different time points--4, 8, 16, 24, 48, 72, and 96 hours, and 7, 10, and 14 days after a footpad injection of 200 micrograms of lipopolysaccharide (LPS). Immunohistochemistry was performed using the monoclonal antibodies ED1 (monocytes, macrophages, dendritic cells), and OX6 (MHC class II antigen). RESULTS: In normal rats, two layers of macrophages were identified in the choroid; a layer located immediately beneath the retinal pigment epithelium (RPE) and a layer bordering the sclera. The density of ED1 positive cells in the layer bordering the RPE cells was 902 (SD 132) cells/mm2 whereas the scleral layer had a cell density of 389 (73) cells/mm2. Based on morphology, positive cells could be divided into two main categories; pleomorphic/round cells and dendritiform cells with varying appearances, with the latter being predominant in normal eyes. A network of MHC class II positive dendritic cells was found in the choroid, beneath the RPE, with a density of 659 (96) cells/mm2. No MHC class II positive cells were found in the macrophage layer bordering the sclera. LPS injection caused a massive influx of ED1 positive macrophages in the area below the RPE cells but did not result in an influx of macrophages at the scleral side of the choroid. The infiltrate reached a maximum at 16 hours following LPS injection and decreased at 96 hours. The morphology of the infiltrating cells was pleomorphic/round at early stages of inflammation and changed into a dendritiform cell population later. The number of MHC class II positive cells on the anterior side of the choroid increased 8 hours after injection and reached a peak at 72-96 hours. MHC class II positive cells were not observed in the vicinity of the sclera at any time after LPS injection. Both resident and MHC class II positive dendritic cell numbers returned to normal values at day 14 following LPS injection. CONCLUSIONS: These results indicate that the choroid is severely inflamed after systemic LPS administration to Lewis rats and suggests that endotoxin induced uveitis may serve as a model for generalised uveitis in humans.

Animals↗

Frequency of asymptomatic choroidal metastasis in patients with disseminated breast cancer: results of a prospective screening programme.

AIM: To determine the frequency of visually asymptomatic choroidal metastasis in patients with disseminated breast cancer and its dependence on the incidence of metastasis by number and site of other organ metastases. METHODS: From January 1995 until April 1997 120 patients irradiated for disseminated breast cancer underwent ophthalmological screening for choroidal metastasis. No patient was symptomatic for ocular disease. 68 out of 120 patients were found to have metastases in one organ and 52 patients had metastases in more than one organ. 80% of the patients had bone metastases, 25% lung metastases, 22% liver metastases, 15% brain metastases, and 22% had metastases in other organs. RESULTS: Six patients (5%) were found to have asymptomatic choroidal metastases. Five patients had unilateral and one patient bilateral metastases. 52 patients with more than one involved organ had a significantly higher risk for asymptomatic choroidal metastasis (6/52, 11%) than 68 patients with metastases in only one organ (0/68) (p = 0.006). In univariate analysis a significantly higher risk was seen for patients with lung metastases (14% choroidal metastases versus 2% in patients without lung metastases, p = 0.03) and for patients with brain metastases (17% choroidal metastases versus 3% in those without brain metastases, p = 0.04). CONCLUSION: In disseminated breast cancer the incidence of asymptomatic choroidal metastases was 5% and increased to 11% when more than one organ was involved in metastatic spread. Risk factors for choroidal metastases were dissemination of disease in more than one organ and the presence of lung and brain metastases.

Adult↗

Choroidal folds and papilloedema.

AIMS: To assess the clinical and fluorescein angiographic features of choroidal folds seen in association with papilloedema. METHODS: In a retrospective study, the clinical data from a database on patients with choroidal folds (1963-97), including fundus photography and fluorescein angiography, from 32 patients (64 eyes) with choroidal folds in association with papilloedema were reviewed. The clinical and fluorescein angiographic features and the clinical course of choroidal folds in these patients are described. RESULTS: 32 patients had choroidal folds associated with papilloedema. Folds of two distinct categories were observed, either coarse folds or wrinkles. The folds persisted in all cases, even after resolution of papilloedema. Follow up ranged from 1 month to 20 years. Only one patient suffered permanent visual impairment as a result of a choroidal fold. CONCLUSIONS: Choroidal folds exist in two forms, coarse folds and wrinkles. They persist even after papilloedema has resolved. Final visual acuity did not appear to be affected by the presence of choroidal folds in the majority of patients.

Adult↗

Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus of cilia-defective Tg737(orpk) mutant mouse.

Tg737(orpk) mice have defects in cilia assembly and develop hydrocephalus in the perinatal period of life. Hydrocephalus is progressive and is thought to be initiated by abnormal ion and water transport across the choroid plexus epithelium. The pathology is further aggravated by the slow and disorganized beating of motile cilia on ependymal cells that contribute to decreased cerebrospinal fluid movement through the ventricles. Previously, we demonstrated that the hydrocephalus phenotype is associated with a marked increase in intracellular cAMP levels in choroid plexus epithelium, which is known to have regulatory effects on ion and fluid movement in many secretory epithelia. To evaluate whether the hydrocephalus in Tg737(orpk) mutants is associated with defects in ion transport, we compared the steady-state pH(i) and Na(+)-dependent transport activities of isolated choroid plexus epithelium tissue from Tg737(orpk) mutant and wild-type mice. The data indicate that Tg737(orpk) mutant choroid plexus epithelium have lower pH(i) and higher Na(+)-dependent HCO(3)(-) transport activity compared with wild-type choroid plexus epithelium. In addition, wild-type choroid plexus epithelium could be converted to a mutant phenotype with regard to the activity of Na(+)-dependent HCO(3)(-) transport by addition of dibutyryl-cAMP and mutant choroid plexus epithelium toward the wild-type phenotype by inhibiting PKA activity with H-89. Together, these data suggest that cilia have an important role in regulating normal physiology of choroid plexus epithelium and that ciliary dysfunction in Tg737(orpk) mutants disrupts a signaling pathway leading to elevated intracellular cAMP levels and aberrant regulation of pH(i) and ion transport activity.

Animals↗

Effects of angiotensin II on blood flow to choroid plexus.

The choroid plexus contains receptors for angiotensin II and a very high concentration of angiotensin-converting enzyme. The goal of this study was to test the hypothesis that angiotensin II decreases blood flow to the choroid plexus. In rabbits anesthetized with chloralose, blood flow (microspheres) to the choroid plexus was 438 +/- 46 (mean +/- SE) ml.min-1.100 g-1 under control conditions. Angiotensin II (10, 30, and 100 ng.kg-1.min-1 iv) decreased blood flow to the choroid plexus by 12 +/- 8, 39 +/- 7, and 57 +/- 5%, respectively, with aortic pressure maintained at control levels. Cerebral blood flow was not affected by angiotensin II. Blood flow to the kidney decreased by 15 +/- 7, 30 +/- 3, and 49 +/- 5%, respectively, during infusion of the three doses of angiotensin II. The angiotensin II antagonist saralasin (1 micrograms.kg-1.min-1 iv) did not affect blood flow to the cerebrum or the choroid plexus under control conditions. Saralasin blocked the vasoconstrictor effect of angiotensin II on the choroid plexus and the kidney. Thus circulating angiotensin II has important and parallel effects on blood flow to the choroid plexus and kidney that are mediated by angiotensin II receptors. We speculate that circulating and perhaps locally produced angiotensin II may play an important role in regulation of blood flow to the choroid plexus.

Angiotensin II↗

Effects of central and intravascular angiotensin I and II on the choroid plexus.

The choroid plexus contains receptors for angiotensin II (ANG II) and a very high concentration of angiotensin-converting enzyme. The goal of this study was to test the hypothesis that central, as well as circulating, ANG I and II decrease blood flow to the choroid plexus. Under control conditions in anesthetized rabbits, blood flow (microspheres) to the choroid plexus was 449 +/- 21 (mean +/- SE) ml.min-1.100 g(-1). Intravascular ANG I (30 and 100 ng.kg-1.min-1) decreased blood flow to the choroid plexus by 19 +/- 14 and 28 +/- 18%, respectively. Intravascular ANG II (30 and 100 ng.kg-1.min-1) also produced a decrease in blood flow by 28 +/- 9 and 47 +/- 7%, respectively. When administered into the lateral ventricle, ANG I and II (10 and 100 ng.kg-1.min-1) decreased blood flow to a similar degree: 22 +/- 11 and 31 +/- 10% and 12 +/- 10 and 27 +/- 8%, respectively. Cerebral blood flow was not decreased by intravascular or central ANG I or II. The angiotensin-converting enzyme inhibitor quinaprilat prevented the decrease in blood flow to the choroid plexus in response to ANG I without affecting responses to ANG II. Thus 1) circulating ANG I and II are potent constrictors of blood vessels of the choroid plexus, 2) the constrictor effect of ANG I on the blood vessels of the choroid plexus appears mediated primarily by generation of ANG II, and 3) intracerebroventricular ANG I produces large reductions in the blood flow to the choroid plexus, which suggests that there is an effective central system that converts ANG I to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗