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Choroidal haemodynamics in glaucoma.

AIM: Quantification of haemodynamics of the peripapillary choroid in and the assessment of possible differences between normal subjects (N), ocular hypertensive (OHT), primary open angle (POAG), and normal pressure glaucoma (NPG) patients. METHODS: Video fluorescein angiograms (Rodenstock SLO 101) were made in 22 N subjects, 12 OHT, 48 POAG, and 46 NPG patients. The angiographically derived dye build up curves were described by means of an exponential model. One of the model parameters is the time constant tau theoretically reflecting local blood refreshment time; the blood refreshment time tau is the time needed to replace the blood volume in the choriocapillaris, inversely proportional to the local choroidal blood flow. Other variables are maximal fluorescence (Fdt) and time of first fluorescence (t0). Mean variable values were calculated for disc area and circular areas around the disc. RESULTS: Fdt of the disc was significantly lower in the POAG and NPG patients. There was no statistical difference in t0 between the study groups. The choroidal blood refreshment time was significantly longer in NPG patients and to a lesser extent in the POAG patients compared with the normal controls. The slowest choroidal blood refreshment can be found in the NPG group. The median choroidal blood refreshment times (25th-75th percentile) in the controls, OHT, POAG, and NPG patients were 4.1 (3.7-4.5), 4.4 (3.7-6.4), 5.8 (4.3-6.8), and 7.1 (5.5-9.3) seconds respectively. CONCLUSIONS: With the help of parametrisation of dye curves, using a one compartmental model, choroidal haemodynamics can be quantified. The blood refreshment time of the peripapillary choriocapillaris was found to be significantly prolonged especially in NPG patients; this may indicate slower choroidal haemodynamics in NPG patients.

Aged↗

Association between choroidal pigmentation and posterior uveal melanoma in a white population.

BACKGROUND/AIMS: It is well known that light skin pigmentation is a risk factor for cutaneous melanoma. The aim of this study was to investigate the analogous association between choroidal pigmentation and posterior uveal melanoma. METHODS: Cross sectional study of 65 consecutive patients diagnosed with posterior uveal melanoma (melanoma group) and 218 consecutive patients referred for general retinal evaluation (control group). All patients were white. A clinical grading system for estimating choroidal pigmentation was developed and histologically validated in seven patients. RESULTS: Melanoma patients with light iris colour were significantly more likely to have darker choroidal pigmentation than controls (p = 0.005). Darker choroidal pigmentation was associated histologically with increased density of choroidal melanocytes (p = 0.005). CONCLUSIONS: Increased choroidal pigmentation, as a result of an increase in the density of pigmented choroidal melanocytes, is not protective but may actually be a risk factor for the development of posterior uveal melanoma in white patients. This finding may have implications for understanding the pathogenesis of uveal melanoma.

Adult↗

Distribution of sodium transporters and aquaporin-1 in the human choroid plexus.

The choroid plexus epithelium secretes electrolytes and fluid in the brain ventricular lumen at high rates. Several channels and ion carriers have been identified as likely mediators of this transport in rodent choroid plexus. This study aimed to map several of these proteins to the human choroid plexus. Immunoperoxidase-histochemistry was employed to determine the cellular and subcellular localization of the proteins. The water channel, aquaporin (AQP) 1, was predominantly situated in the apical plasma membrane domain, although distinct basolateral and endothelial immunoreactivity was also observed. The Na(+)-K(+)-ATPase alpha(1)-subunit was exclusively localized apically in the human choroid plexus epithelial cells. Immunoreactivity for the Na(+)-K(+)-2Cl(-) cotransporter, NKCC1, was likewise confined to the apical plasma membrane domain of the epithelium. The Cl(-)/HCO(3)(-) exchanger, AE2, was localized basolaterally, as was the Na(+)-dependent Cl(-)/HCO(3)(-) exchanger, NCBE, and the electroneutral Na(+)-HCO(3)(-) cotransporter, NBCn1. No immunoreactivity was found toward the Na(+)-dependent acid/base transporters NHE1 or NBCe2. Hence, the human choroid plexus epithelium displays an almost identical distribution pattern of water channels and Na(+) transporters as the rat and mouse choroid plexus. This general cross species pattern suggests central roles for these transporters in choroid plexus functions such as cerebrospinal fluid production.

Amino Acid Sequence↗

Effects of vasoactive stimuli on blood flow to choroid plexus.

The goal of this study was to examine effects of vasoactive stimuli on blood flow to choroid plexus. We used microspheres to measure blood flow to choroid plexus and cerebrum in anesthetized dogs and rabbits. A critical assumption of the microsphere method is that microspheres do not pass through arteriovenous shunts. Blood flow values obtained with simultaneous injection of 15- and 50-micron microspheres were similar, which suggests that shunting of 15-micron microspheres was minimal. Blood flow to choroid plexus under control conditions was 287 +/- 26 (means +/- SE) ml.min-1.100 g-1 in dogs and 385 +/- 73 ml.min-1.100 g-1 in rabbits. Consecutive measurements under control conditions indicated that values for blood flow are reproducible. Adenosine (5 microM.kg-1. min-1 iv) did not alter blood flow to cerebrum but increased blood flow to choroid plexus two- to threefold in dogs and rabbits. Norepinephrine (0.5 micrograms.kg-1.min-1) and phenylephrine (25 micrograms.kg-1.min-1) did not affect blood flow to cerebrum but decreased blood flow to choroid plexus by approximately 50%. We suggest that 1) the microsphere method provides reproducible valid measurements of blood flow to the choroid plexus in dogs and rabbits and 2) vasoactive stimuli may have profoundly different effects on blood flow to choroid plexus and cerebrum.

Adenosine↗

Effect of atriopeptin on blood flow to cerebrum and choroid plexus.

The goal of this study was to determine whether atriopeptin alters blood flow to cerebrum and choroid plexus. In anesthetized rabbits, blood flow (microspheres) to cerebrum and choroid plexus under control conditions was 36 +/- 3 (mean +/- SE) and 573 +/- 78 ml.min-1.100 g-1, respectively. Infusion of atriopeptin (75, 225, 1,150 ng.kg-1.min-1 iv) increased blood flow to choroid plexus by 22 +/- 11, 53 +/- 26, and 51 +/- 13%, respectively. In contrast, blood flow to cerebrum was not altered by atriopeptin, presumably because the blood-brain barrier prevented access to cerebral vascular smooth muscle. Because a major role of atriopeptin may be to modulate responses to angiotensin II, we examined effects of atriopeptin on vasoconstrictor responses to angiotensin II in the choroid plexus. Angiotensin II was infused in the presence or absence of atriopeptin (300 ng.kg-1.min-1 iv). Angiotensin II (100 ng.kg-1.min-1 iv) decreased blood flow to choroid plexus by 49 +/- 12% and by 47 +/- 14% during simultaneous infusion of atriopeptin. In summary, atriopeptin 1) increases blood flow to choroid plexus, but not cerebrum, and 2) does not appear to attenuate vasoconstrictor effects of angiotensin II in the choroid plexus.

Animals↗

Secretory response of mast cells contained in monodispersed human choroidal preparations.

BACKGROUND: Mast cells have been identified in the choroid of numerous species including man. However, functional studies involving these human mast cells have not been reported. In the current studies, the secretory response of human choroidal mast cells to various stimuli was examined using monodispersed choroidal cell preparations. METHODS: Monodispersed cell suspensions of human choroid were prepared from eye bank globes and the number, histamine content, and secretory response of mast cells in these preparations were determined. Choroids from 27 donors were used for these experiments. RESULTS: Cell suspensions contained an average of 15% mast cells. Mast cells stained positively with toluidine blue and exhibited the classical granular appearance upon electron microscopy. The amount of histamine contained in each mast cell was calculated to be 2.74+/-0.17 pg. Significant histamine release was observed following treatment with anti-human IgE, calcium ionophore A23187, concanavalin A, compound 48/80 and morphine. CONCLUSION: A method has been developed for obtaining monodispersed human choroidal mast cell preparations. The cells were functional as evidenced by their ability to release histamine upon immunological and nonimmunological stimulation. The degranulation noted following compound 48/80 and morphine challenge suggests that these human choroidal mast cells are analogous to connective tissue or chymase/tryptase-positive mast cells.

Antigens, Surface↗

Isolated fetal choroid plexus cysts: not an indication for genetic diagnosis?

Offering invasive prenatal cytogenetic testing in cases of isolated choroid plexus cysts is controversial. To give a contribution to this discussion we recorded prospectively the course of 41 fetuses with cysts of the choroid plexus diagnosed in 4,326 pregnancies sonographically scanned in our center between January 1994 and August 1995. The fetuses were all in the 13th to 24th week of gestation, with an average of 19.3 weeks. Only 1 of these fetuses (with large bilateral choroid plexus cysts) had further sonographically visible malformations (renal and cardiac anomalies, malposition of the hands). 34 fetuses had bilateral and 7 one-sided plexus cysts. 38 of the 41 patients decided on invasive diagnosis; karyotyping was successful in all these cases. The complete follow-up until 5 days after birth is known in 38 fetuses, including 3 without genetic diagnosis. A chromosomal aberration was detectable only in 1 fetus (trisomy 18, this fetus had the additional malformations described above), the other fetuses all displaying neither chromosomal nor morphological abnormalities. All fetuses, excluding 1 (the pregnancy was terminated due to trisomy 18) were re-examined before the 25th week of gestation, plexus cysts only still being visible in 3 fetuses. By the 30th week of gestation in these 3 fetuses the cysts had also disappeared. Furthermore, 20 pregnancies with confirmed trisomy 18 diagnosed between 1990 and 1996 were analyzed retrospectively. In 19 cases heart defects had been detected by prenatal ultrasound, cervical hygroma being less common (6 cases) and other malformations still rarer. Choroid plexus cysts had, however, been seen only in the 1 case described above. There was no case of isolated choroid plexus cysts in this group. From our data and current literature we conclude that isolated choroid plexus cysts are not an absolute indication for fetal karyotyping. In our opinion a detailed ultrasound assessment to seek for further malformations in a specialized center would be necessary if fetal choroid plexus cysts have been diagnosed, and only if additional fetal malformations are indeed detectable a fetal karyotype should be recommended.

Adult↗

Presence of a contractile cell network in the human choroid.

Immunohistochemical staining of choroidal whole mounts as well as serial tangential sections and electron-microscopic investigation of 21 human donor eyes revealed a network of nonvascular alpha-smooth-muscle-actin-positive cells (NVSMC) in the entire choroid most densely arranged in the posterior part of the suprachoroid of the submacular region. Ultrastructurally these cells present the typical structure of myofibroblasts. Double labeling with desmin and smooth muscle myosin showed a positive reaction only in few of these cells. Posteriorly the NVSMC net reaches the optic nerve, anteriorly it ends in the region of the vortex veins but does not continue into the ciliary muscle. In places, intimate contact between the contractile cells and the elastic fiber network of the choroidal stroma and the perivascular sheaths is seen. The elastic net of the choroid is firmly connected with the posterior elastic tendons of the ciliary muscle. In the course of accommodation, the ciliary muscle pulls this net foreward presumably influencing position and diameter of the choroidal vessels. We assume that the network of NVSMC of the choroid counteracts the ciliary body movements during accommodation, thus guaranteeing the three-dimensional architecture of the choroid and the position of the retina, particularly in the macular region.

Actins↗

The influence of path length and matrix components on ageing characteristics of transport between the choroid and the outer retina.

PURPOSE: To determine the relative influence of path length and matrix components on the movement of small solutes and water between the choroid and the outer retina. METHODS: Human and bovine Bruch's membrane-choroid (BC) tissue samples were mounted in modified Ussing chambers, and the diffusion of taurine and hydraulic conductivity (Lp) was determined. In humans, diffusion of taurine was determined as a function of age of the donor. The relative contribution of Bruch's membrane in the BC complex to transport processes was measured after its removal by laser ablation. Similarly, the effect of choroidal path length was determined. In humans, tracking the trend of age-related thinning provided samples of various path lengths. In young bovine animals (< or =2 years old), choroidal thickness was adjusted by laser ablation. RESULTS: Diffusion of taurine across human BC decreased linearly from 162.7 to 105.9 nanomoles/h per 3 mm between 10 and 90 years of age (P < 0.05). Ablation of Bruch's membrane increased diffusion of taurine from 129 to 287.9 nanomoles/h per 4 mm in human (donor age 55, 74, and 82 years; P < 0.005) but caused no statistically significant change in bovine BC. Diffusion of taurine across bovine BC was greater in samples with partially ablated choroid (218 nanomoles/h per 4 mm) than in normal control samples (128.75 nanomoles/h per 4 mm). Lp was not measurable in bovine samples after complete ablation of Bruch's membrane, but did not change significantly as the choroid thinned. CONCLUSIONS: The data suggest that both path length and matrix components contribute to the decline of diffusion of small solutes across BC with age. The importance of matrix components was also demonstrated in restricting the movement of water while choroidal thickness played little if any role.

Adolescent↗

The fodrin-ankyrin cytoskeleton of choroid plexus preferentially colocalizes with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2.

A unique feature of the choroid plexus as a single-layer epithelium is its localization of Na+K(+)-ATPase at its apical (lumenal) surface. In contrast, a band 3 (AE1)-related anion exchanger protein has been localized to the basolateral surface of the choroid plexus. Both Na+K(+)-ATPase and AE1 in other tissues have been shown to bind via ankyrin to the spectrin-actin-based membrane cytoskeleton. Since linkage of integral membrane proteins to the membrane cytoskeleton is important for their restriction to specialized domains of the cell surface, we investigated the polarity of the choroid plexus membrane cytoskeleton. We developed isoform-specific antibodies to confirm the identity of choroid plexus band 3-related polypeptide as AE2. We demonstrated that ankyrin, fodrin/spectrin, actin, myosin, and alpha-actinin are predominantly apical in choroid plexus and preferentially colocalize with apical Na+K(+)-ATPase rather than with basolateral anion exchanger AE2. Colchicine administration did not alter the polarity of apical cytoskeletal and transport proteins or basolateral AE2 in choroid plexus, suggesting that biosynthetic targeting of these proteins is not microtubule dependent. In choroid plexus papilloma, Na+K(+)-ATPase and AE2 were decreased in amount and failed to preserve their polarized distributions.

Animals↗

Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy: a report of three cases.

PURPOSE: To report three cases of bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy. METHODS: Retrospective, single-center case series. RESULTS: Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm-thick choroidal melanoma in the right eye (OD) and treated with plaque radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was treated with plaque radiotherapy. Final visual acuity was light perception OD and 20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a 7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow-up. No patient showed ocular melanocytosis. Stable tumor regression was achieved in all six eyes. Metastatic disease did not develop in any case over 16 years of follow-up. CONCLUSIONS: Monitoring of both eyes of patients with uveal melanoma is important for the remote possibility of melanoma in the second eye. In these three patients, plaque radiotherapy allowed for preservation of the globes and some vision.

Aged, 80 and over↗

Choroid plexus infection in cerebral toxoplasmosis in AIDS patients.

We evaluated the postmortem incidence of choroid plexus infection in cerebral toxoplasmosis in 17 patients with acquired immune deficiency syndrome (AIDS) and cerebral toxoplasmosis and, by immunohistochemistry, identified Toxoplasma gondii tachyzoites in this structure in 53% of all cases. They were present in 78% of the nine cases with the acute necrotizing stages of CNS toxoplasmosis but were less frequent (20%) in patients with only the healed cystic lesions of toxoplasmosis. Large necrotizing abscesses of the choroid plexus were found in three of the patients. In one of these, the choroid plexus was the sole site of CNS infection, which presented as radiographically documented masses in the third and fourth ventricles associated with obstructive hydrocephalus. These results demonstrate that infection of the choroid plexus is common with cerebral toxoplasmosis and suggest that this infection should be included in the differential diagnosis of intra- or periventricular lesions in patients with AIDS. In addition, the high frequency of choroid plexus infection with acute cerebral toxoplasmosis suggests that cerebral toxoplasmosis in the immunosuppressed patient may be due to hematogenous spread to the choroid plexus from reactivation of latent organisms from systemic organs rather than to reactivation of latent organisms within the brain itself. Furthermore, the high frequency of choroid plexitis offers the potential for CSF dissemination of this infection.

AIDS-Related Opportunistic Infections↗

Capacity to form choroid plexus-like cells in vitro is restricted to specific regions of the mouse neural ectoderm.

Neural ectoderm was dissected from 9.5-day and 8.5-day gestation mouse embryos and divided into forebrain, midbrain, hindbrain and spinal cord regions. Forebrain and hindbrain material from 9.5-day neural ectoderm was further divided into presumptive choroid plexus regions and regions that would normally form nervous tissue in vivo. All tissues were plated onto a basement membrane substratum for culture in vitro. It was found that explants of neural ectoderm that would normally form choroid plexus in vivo, readily differentiated to form choroid plexus-like cells in culture. Cells from hindbrain segments and forebrain regions, which would normally form nervous tissue, also had the potential to differentiate into cells resembling the choroid plexus epithelium in culture, provided that the normal cell-cell interactions were disrupted. Cells from the midbrain neuromeres of 9.5-day embryos, which do not form a choroid plexus in vivo, did not form this lineage in vitro. However, cells cultured from the earlier head-fold stage midbrain neural ectoderm could develop into choroid plexus epithelium. There was no evidence that neural ectoderm from the spinal cord had the developmental potential to form choroid plexus epithelial cells at either of these two developmental stages. These studies show that the restrictions in the potential of neural ectoderm stem cells to form different lineages proceeds according to morphological divisions that appear along the anterior-posterior axis during the early stages of brain development. These results suggest that the division of neural ectoderm into segments which contain discrete stem cell populations may be a general feature of the early phase of development of the central nervous system.

Animals↗

Na,K-, Mg- and HCO3-adenosine triphosphatases in the rabbit brain choroid plexus.

Properties of adenosine triphosphatases (ATPases) in the choroid plexus of rabbit cerebral ventricles were investigated using tissue homogenates and subcellular fractions. Na,K-ATPase or HCO3-ATPase activity of choroid plexus was significantly lower than that of the brain or the kidney, respectively. Among the homogenates of choroid plexus from the lateral, third and fourth ventricles, there were no differences in the activities of Na,K-, Mg- and HCO3-ATPases. In the choroid plexus, Na,K-ATPase activity was demonstrated to be highest in 10,000 X g fraction, while the highest Mg- and HCO3-ATPase activities were observed in 8,000 X g fraction, the so-called mitochondrial fraction. Ion requirement, pH optimum and ouabain sensitivity of Na,K-ATPase in 10,000 X g fraction of choroid plexus were similar to findings in erythrocytes, brain and kidney. However, properties of Mg- and HCO3-ATPases in 8,000 X g fraction were considerably different from those found in the brain and gastric mucosa. In the choroid plexus, thiocyanate ion inhibited Mg-ATPase as well as HCO3-ATPase. These results indicate that characteristics of ATPase systems in the choroid plexus are to some extent different from those in tissues such as brain, kidney and gastric mucosa.

Adenosine Triphosphatases↗

Physical and chemical characterization of iris and choroid melanosomes isolated from newborn and mature cows.

Bovine iris and choroid melanosomes at two ages (<1 week and >2 years) were examined by inductively coupled plasma mass spectrometry (ICP-MS), elemental analysis, infrared spectrometry (IR) and X-ray photoelectron spectrometry (XPS). When iris and choroid melanosomes at the same age were compared, the quantification of metal elements by ICP-MS revealed that choroid melanosomes had a higher binding capacity for the carboxylate-binding metal ions (e.g. Na+ K+, Mg2+, Ca2+ and Zn2+). Elemental analysis showed a higher O:N ratio in choroid melanosomes. Both observations suggested that choroid melanosomes have a higher content of carboxylate-containing monomer than iris melanosomes. IR spectrometric analysis showed a red shift (approximately 8 cm(-1)) of the absorption peak of aromatic C=C, C=N and C=O at approximately 1630 cm(-1) in the IR spectrum of iris melanosomes relative to choroid melanosomes. Increased conjugation in the molecular structure of the pigment is proposed to contribute to this peak shift. It is also notable that although the elemental analysis showed different C, N and O contents in the two types of melanosomes, XPS showed almost the same elemental compositions on the surface of two types of iris and choroid melanosomes studied. When the melanosomes from the same tissues at different ages were compared, ICP-MS analysis suggested that the number of carboxylate groups in the melanosomes decreased with age. Both elemental analysis and XPS showed that C:N ratio decreased with age, which was proposed to be due to both a decrease in carboxylate groups in mature samples and to the fissure of phenol rings caused by age-associated oxidation. Such age-related oxidative damage diminishes conjugation and is manifested by blue shifts of absorption peaks for aromatic double bonds in the IR spectra of mature melanosomes. XPS analysis showed that the ratio of C-O:C=O decreased with age. These tissue-related and age-related chemical differences between samples affected the optic density and metal binding properties of melanosomes, which are believed to be closely associated with the biological functions of melanins.

Aged↗

Differential effects of diabetes on rat choroid plexus ion transporter expression.

Though diabetes is a disease with vascular complications, little is known about its effects on the blood-brain barrier or the blood-cerebrospinal fluid barrier (BCSFB). The BCSFB is situated at choroid plexuses located in the lateral, third, and fourth ventricles. Choroid plexuses are the primary site of cerebrospinal fluid (CSF) production and express numerous ion transporters. Previous studies have shown a perturbation of ion transport in the periphery and brain during diabetes. In this study, we investigated the effect of diabetes on ion transporters in the choroid plexuses of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of STZ (60 mg/kg in citrate buffer, confirmed by glucose analysis: 601 +/- 22 mg/dl diabetic rats, 181 +/- 46 mg/dl age-matched controls); and at 28 days, rats were killed, choroid plexuses harvested, and protein extracted. Western blot analyses were carried out using antibodies for ion transporters, including Na(+)-K(+)-2Cl(-) cotransporter and the Na(+)-K(+)-ATPase alpha1-subunit. The efflux of the K(+) analog (86)Rb(+) from choroid plexus was also studied. Diabetic rats showed an increase in expression of the Na(+)-K(+)-2Cl(-) cotransporter and the Na(+)-K(+)-ATPase alpha1-subunit, as compared with age-matched controls, a decrease in Na(+)-H(+) exchanger expression, and no change in Na(+)-K(+)-ATPase beta1- or beta2-subunit. The net effect of these changes was a 66% increase in (86)Rb(+) efflux from diabetic choroid plexus compared with controls. These changes in expression may affect choroid plexus ion balance and thus significantly affect CSF production in diabetic rats.

Animals↗

Time change of nicardipine effect on choroidal circulation in rabbit eyes.

PURPOSE: To investigate the time course of effects of intravenous administration of a calcium antagonist, nicardipine, on the choroidal circulation of rabbit eyes using a laser speckle tissue circulation analyzer. METHOD: The rabbit fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB); a quantitative index of tissue blood velocity. The average NB over the field measured (0.620.62 mm in the choroid) was calculated to give Nb(av). Under general anesthesia, 0.4 ml/kg of 0.01% nicardipine hydrochloride dissolved in physiological saline was injected intravenously in a group of albino rabbits (control group) for measurement in the choroid (nicardipine groups). To serve as control, 0.4 ml/kg of physiological saline was injected in other groups of albino rabbits (control groups). Nb(av) was recorded at 1-min intervals for the first 5 min and at 5-min intervals for the next 85 min. During the experiment mean femoral arterial blood pressure (FABPm), pulse rate (PR), arterial blood pH, Pco2 and Po2 body temperature (BT) and intraocular pressure (IOP) were also monitored. Before and 45 min after nicardipine administration, the choroidal blood flow measurement using the microsphere technique and the Nb(av) measurement were carried out in the same eye in another group of rabbits. RESULTS: Only the rabbits which did not show any significant change in the PR, pH, Pco2, Po2 and BT during the experiment were accepted. FABPm in the nicardipine group dropped to the minimum at 1 min postadministration and this level remained significantly lower than that in the control group up to 15 min post-injection, while te 10P did not show any significant change. The Nb(av) in the nicardipine group showed a significant increase after the FABPm return to the baseline, which was maintained throughout the experiment. The averaged increase between 30 and 90 minutes after administration was 27 +/- 1% (mean +/- S.E.M., n = 10). Relative increase in choroidal blood flow determined by the microsphere technique showed a good correlation (r = 0.90, P < 0.001, n = 12) with those determined by Nb(av) after nicardipine administration. CONCLUSIONS: The present result indicates that the time course of drug effects on the choroidal circulation can be noninvasively and sensitively followed by Nb(av) measurements. Further, it was shown that nicardipine may have considerable potential for the treatment of ocular diseases associated with insufficient choroidal blood flow and that nicardipine's effects here observed deserve to be further studied in humans.

Animals↗

Choroid plexus as a barrier to immunoglobulin delivery into cerebrospinal fluid.

The concentration of gamma globulins is greatly increased in the cerebrospinal fluid (CSF) during inflammatory and degenerative disorders of the central nervous system (CNS). The mechanism by which immunoglobulins enter the CSF under normal conditions is unknown. The extent of participation of the blood-brain barrier in protein delivery to the CSF is unclear, although the choroid plexus is known to have primary responsibility for the formation and movement of certain proteins into the CSF. To investigate the role of the choroid plexus in immunoglobulin delivery to the CSF, the authors evaluated rat brain tissue by light and electron microscopic immunohistochemical technique using the peroxidase technique of immunoglobulin (Ig)G and IgA detection. Peanut agglutinin was used to identify macrophages, cells known to have important immune functions and which have been reported as a normal component of the choroid plexus. Antisera to IgG' and IgA demonstrated diffuse surface staining of the choroidal epithelial cells with light and electron microscopy; the cytoplasm and nuclei did not contain immunoglobulins. Macrophages were not present in the choroid plexus, in contrast to previous reports. The results demonstrate that immunoglobulins do not enter the CSF via the choroid plexus, unlike other proteins in similar concentrations in the CSF. In addition, macrophages are shown to be an insignificant component of the plexus, thereby further diminishing the likelihood of participation-of the choroid plexus in the regulation of immunoglobulin entry into the CNS under normal conditions.

Animals↗