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Endothelin modulation of choroidal blood flow in the rabbit.

Based on the previous finding that locally produced nitric oxide (NO) and endothelin (ET) exert competing effects on choroidal resistance vessels, the present study sought to further characterize the pharmacology of ET in the choroid. The specific goal was to quantify the choroidal blood flow responses to acute changes in perfusion pressure before and after administering endothelin 1 (ET1), a non-selective ET antagonist, and selective antagonists for the endothelin A (ETA) and endothelin B (ETB) receptor subtypes. Anesthetized rabbits were instrumented with an ear artery cannula to measure mean arterial pressure (MAP), occluders on the aorta and vena cava to control MAP, and a vitreous cannula to measure intraocular pressure (IOP). Choroidal blood flow was measured by laser Doppler flowmetry with a vitreous fiber optic probe. The protocol entailed changing the ocular perfusion pressure by varying MAP before and after ET1 (0.9 microg kg(-1), i.v., n = 14), non-selective ET blockade (A-182086, 3 mg kg(-1), i.v., n = 10), selective ETA blockade (FR-139317, 3 mg kg(-1), i.v., n = 12), and selective ETB blockade (A-192621, 3 mg kg(-1), i.v., n = 14). ET1 and ETB blockade shifted the choroidal pressure-flow relation downward, while the non-selective antagonist and the selective ETA antagonist had no effect. The choroid had a biphasic response to exogenous ET1 as seen in other tissues (i.e. initial brief dilation followed by prolonged constriction) that was blocked by the non-selective antagonist whereas the ETA antagonist enhanced the dilation and blocked the constriction, and the ETB antagonist blocked the dilation and enhanced the constriction. These results indicate that ETA and ETB receptors are present and mediate opposing effects on choroidal vascular resistance. The results also suggest that endogenous ET preferentially elicits ETB vasodilation, most likely by stimulating endothelial nitric oxide release.

Animals↗

Intrinsic neurons in the duck choroid are contacted by CGRP-immunoreactive nerve fibres: evidence for a local pre-central reflex arc in the eye.

Intrinsic choroidal neurons represent peripherally displaced autonomic nerve cells supposed to work as a local integrative network similar to the enteric nervous system, to control choroidal vasculature and stromal smooth muscle. A typical feature of such intramural neuronal networks is the innervation by primary afferent collaterals expressing peptides, e.g. CGRP. The present study was aimed at determining primary afferent contacts on nitrergic intrinsic choroidal neurons (ICN) in the duck eye. In addition, a sympathetic innervation of ICN was assessed. Choroids were immunohistochemically processed for the following markers: neuronal nitric oxide synthase (nNOS), galanin (GAL), calcitonin gene-related peptide (CGRP), and tyrosine hydroxylase (TH). For evaluation, fluorescence as well as confocal laser scanning microscopy were used. For electron microscopy, immunoperoxidase staining for CGRP in combination with NADPH-diaphorase histochemistry was applied. ICN immunoreactive for nNOS or GAL spread over the entire choroid, although they were concentrated in an equatorial zone passing obliquely from naso-cranial to temporo-caudal. About 40% of ICN showed close relationships with CGRP-immunoreactive nerve fibres, originating most likely in the trigeminal ganglion, as seen in the fluorescence and confocal laserscanning microscope. These appositions could be ultrastructurally defined as both synapses and close contacts without synaptic specialization. Some ICN endowed with CGRP-positive fibres also received TH-immunoreactive boutons. CGRP-immunoreactive profiles were also detected in close relationship to choroidal non-vascular smooth muscle cells and collagen fibres connected to them. In many instances, they were intercalated between smooth muscle cells and processes of ICN forming triads. These results suggest that ICN, similar to other intramural autonomic systems integrate signals from trigeminal primary afferent collaterals. The 'sensory' terminals of these primary afferents may be located in the anterior eye segment but also within the smooth muscle stroma of the choroid itself. Thus, ocular homeostasis may be regulated via intraocular pre-central reflexes which are probably subject to sympathetic modulation.

Afferent Pathways↗

An extensive system of extravascular smooth muscle cells exists in the choroid of the rabbit eye.

We investigated the structural organization of the choroid especially with regard to the presence of extravascular smooth muscle (EVSM) cells in albino rabbits. The eyes were fixed by intracardiac perfusion and processed for light, confocal, and electron microscopy. An unlabeled monoclonal antibody against alpha-actin of smooth muscle and a horseradish-peroxidase-conjugated secondary antibody were used for immunodetection of smooth muscle actin by light microscopy. For confocal microscopy, whole mount choroids were immunostained with a fluorescein isothiocyanate-conjugated (FITC) antibody. Our investigations revealed that the choroidal vessels are enveloped by bundles of EVSM. In contrast to the circular orientation of the smooth muscle cells of the tunica media of the choroidal vessels, the cells of the EVSM system were oriented longitudinally along the external surface of the vessel wall. The EVSM cells were strongly immunopositive for smooth muscle alpha-actin and exhibited a green fluorescence of the FITC-labeled anti-alpha-actin antibody. Individual cells were elongated and spindle-shaped, had the usual ultrastructural features of smooth muscle cells and, in places, were organized as 20 layers. EVSM cells were present throughout the thickness of the choroid, but not between the fenestrated endothelial lining of the choriocapillaris and Bruch's membrane, and extended from the optic nerve to the ciliary body where they merged with the ciliary muscles. Based on the three dimensional organization, immunoreactivity, and cellular and subcellular features of the EVSM system as well as information in the literature, we hypothesize that, functionally, this system, in conjunction with the choroidal vasculature, contributes to the myogenic control of choroidal blood flow and tissue volume, and also affects the intraocular pressure as well as the refractive and accommodative state of the eye.

Actins↗

Indocyanine green angiographic findings in idiopathic choroidal neovascularization.

PURPOSE: Evaluation of choroidal alterations associated with idiopathic choroidal neovascularization (ICNV) and the possible relation between this affection and Multifocal Choroidopathies (MC). METHODS: The authors analysed, using high definition videoangiography, the choroidal findings in 21 consecutive patients affected by ICNV (7 males and 14 females; 19-46 years; mean age: 31.8 years); with a follow-up at 5-30 months (mean 13 months). Moreover, a retrospective study of 20 cases of ICNV (11 males and 9 females; age: 17-39 years; mean age: 29.3 years) with a follow-up at 6-11 years (mean 8.9), was performed. RESULTS: In 7 eyes, the indocyanine green angiography (ICGA) showed choroidal hypofluorescent spots similar to those observed in MC (in 3 cases even in the fellow unaffected eye), in 2 of them the regression of the spots was observed after steroid therapy. In 2 eyes, the ICGA revealed hyperfluorescent spots; in one of them the complete regression of the spots after oral cyprofloxacine was observed. In 6 patients (10 eyes), choroidal permeability alterations could be visualized (in 4 cases even in the unaffected eye). CONCLUSIONS: The indocyanine green angiographic findings (hypo and hyperfluorescent spots, choroidal permeability alterations) could support the theory of Gass which considers that ICNV is not idiopathic but secondary to a widespread choroidal inflammatory disease. The similarity of the ICGA alterations in ICNV and MC, the observation that cases of ICNV would become MC in the follow-up, could allow the hypothesis of a close connection between these two affections.

Adolescent↗

Characterization of lactogen binding sites in choroid plexus.

Prolactin binding sites have been demonstrated previously in rat choroid plexus using in vivo radioautography (Walsh et al. 1978). In the present study we have employed this procedure to characterize further the binding specificity of these sites. Following the injection of 125I-hGH or 125I-oPRL an intense radioautographic reaction was observed over the choroid plexus. The reaction was significantly reduced by coinjecting excess unlabeled hGH or oPRL but not bGH. The specific binding of 125I-oPRL to choroid plexus from rat, rabbit, sheep and pig was demonstrated by in vitro assays. Subsequently a survey of 125I-oPRL specific binding in a number of regions of pig brain indicated that the highest binding was in choroid plexus. A detailed study of the characteristics of 125I-oPRL binding to pig choroid plexus was undertaken. Specific binding increased with choroid plexus homogenate protein to a maximum of 30% (3.0 mg protein/tube). Binding was maximum at 4 degrees C by 30-40 h of incubation. During the incubation the integrity of 125I-oPRL in the incubation medium declined steadily to 50% after 20 h and 35-40% after 48 h. Radioactivity eluted from binding sites was fully intact as judged by rebinding to lactogen receptor-enriched membranes. Binding showed a broad pH optimum of 5.5-7.5. On cell fractionation of choroid plexus binding sites were enriched in microsomes. The binding of 125I-oPRL and 125I-hGH was inhibited in a dose-dependent manner by unlabeled lactogens and was of high affinity. hGH and oPRL were equipotent inhibitors of the binding of both radioligands whereas bGH and a variety of structurally unrelated peptides were non-inhibitory.

Animals↗

Changes in the choroid plexus, responses by intrinsic epiplexus cells and recruitment from monocytes after experimental head acceleration injury in the non-human primate.

We have examined, by scanning and transmission electron microscopy, morphological changes in the choroid plexus of the lateral ventricles of the non-human primate brain after lateral head acceleration. We demonstrate passage of plasma and blood cells either through tears in blood vessels and the choroidal epithelium, or through the cells of the choroidal epithelium, 20 min after injury, together with morphological changes in that epithelium. At 3 and 4 h small cells with a reniform nucleus accumulate in the connective tissue core of the choroid plexus. We suggest that these are monocytes. At 6 and 12 h cells can be seen in enlarged intercellular spaces within the choroidal epithelium. These cells possess surface ruffles and we suggest that they are monocytes differentiating into macrophages and epiplexus cells. Further evidence for transepithelial migration of monocytes/macrophages is obtained at 7 days. However, at 28 days all blood has been removed from the surface of the choroid plexus and epiplexus cells possess an appearance typical of that in uninjured animals. The possible sources of epiplexus cells are discussed with reference to studies of responses after brain insult and of development. We have obtained no evidence in support of emperipolesis by monocytes through the choroidal epithelium. We suggest that monocytes/macrophages migrate, via an intercellular route, to differentiate into epiplexus cells, thus providing additional numbers of epiplexus cells after head injury.

Acceleration↗

Monoclonal antibodies in detection of choroidal melanoma.

Three monoclonal antibodies (MoAbs) prepared against cutaneous melanomas were tested against one group of 12 choroidal melanomas with indirect immunofluorescence in frozen sections. A fourth MoAb was tested in paraffin sections of a second group of 47 choroidal melanomas. One MoAb (NKI-M7) did not react with choroidal melanoma, even though it had a high sensitivity for cutaneous melanoma. A second MoAb (NKI-M6) showed a positive reaction with only 2/12 choroidal melanomas. The third MoAb (NKI/beteb) reacted with all choroidal melanomas, regardless of the cell type. MoAb NKI/C-3 was positive with 38/47 (81%) choroidal melanomas. We conclude that NKI/C-3 and NKI/beteb have a high sensitivity for both cutaneous and choroidal melanomas in frozen sections. Of these two antibodies NKI/beteb was the most specific for cutaneous naevi and melanomas.

Antibodies, Monoclonal↗

Transthyretin distribution in the developing choroid plexus of the South American opossum (Monodelphis domestica).

The distributions of transthyretin and albumin in the choroid plexus during brain development have been compared. The South American opossum was chosen because the young are born around the time of choroid plexus formation. Previous work showed that in the adult opossum, transthyretin is expressed in the choroid plexus cells. However, systematic studies of transthyretin in the choroid plexus during development have not been carried out before. Transthyretin was present in 90-95% of the choroidal cells form birth to adulthood. In most cells, transthyretin immunoreactivity was concentrated in the apical region of the cytoplasm. Double labelling of choroid plexus sections with antibodies to albumin and transthyretin showed that 1-2% of cells were positive for both proteins. These findings suggest that from the very earliest stage of choroid plexus formation most epithelial cells both synthesize and contain transthyretin, and a few of these transthyretin-synthesizing cells also contain albumin that is probably being transferred form blood to the cerebrospinal fluid.

Age Factors↗

Effects of endothelin on blood vessels of the brain and choroid plexus.

Endothelin is a recently described vasoactive peptide produced by endothelial cells. Receptors for endothelin are found throughout the brain, and are particularly dense in the choroid plexus. Effects of endothelin on cerebral blood flow and blood flow to the choroid plexus are not known. In this study, we examined effects of endothelin (100 and 1000 ng/kg i.v.) on regional blood flow (microspheres) and cerebral microvascular pressure in anesthetized rabbits. Endothelin (1000 ng/kg) produced only a 4 +/- 2 mm Hg (mean +/- S.E.M.) increase in systemic blood pressure, and had no effect on cerebral blood flow or cerebral microvascular pressure. In contrast, endothelin produced a marked decrease in blood flow to the choroid plexus and dura mater. Blood flow to choroid and dura remained significantly decreased 1 h after administration of the peptide. Endothelin also reduced blood flow to the kidney and small intestine, but the decreases tended to be less than in choroid plexus or dura mater. Thus, circulating endothelin, at doses that have no effect on cerebral blood vessels, has marked effects on blood flow to the choroid plexus. These findings suggest that circulating or locally produced endothelin may contribute to regulation of brain fluid balance through effects on choroid plexus and production of cerebrospinal fluid.

Animals↗

Expression of neuropeptide processing enzymes and neurosecretory proteins in ependyma and choroid plexus epithelium.

Recent studies suggest that brain ependyma and choroid plexus produce neuropeptide processing enzymes. To facilitate the understanding of these cells and their ability to produce biologically active peptides, we developed cultures of defined cell type. Ependymal cells were characterized by morphological criteria, and choroid plexus epithelial cell lines were characterized by the presence of the mRNA for IGF-II and transthyretin, a thyroxine binding protein produced in liver and choroid plexus. The ependymal cells and the choroid plexus epithelial cell lines were then examined for the presence of mRNAs for various neuropeptide processing enzymes. Northern blot analysis revealed high levels of furin, carboxypeptidase E, and peptidyl glycine alpha-amidating monooxygenase mRNAs, with levels in ependymal cells comparable to those in brain or pituitary. Carboxypeptidase E activity was detected in medium from cultured ependymal cells; this activity was identified as carboxypeptidase E based on the acidic pH optimum and sensitivity to various inhibitors. The mRNAs for other neuropeptide processing enzymes, such as prohormone convertases 1 and 2, were not detected on Northern blots of RNA from ependyma or choroid plexus epithelium. Since ependyma and choroid plexus epithelium express a subset of processing enzymes, we suggest that these cells have the capacity to produce biologically active peptides. Initial screening by reverse transcriptase-polymerase chain reaction assays has demonstrated the presence of mRNA for the neurosecretory proteins chromogranin B and secretogranin II in both ependyma and choroid plexus epithelium.

Animals↗

An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges.

Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.

5,7-Dihydroxytryptamine↗

Developmental patterns of gene expression of secreted proteins in brain and choroid plexus.

The proteins secreted by the choroid plexus throughout rat brain development were analyzed by two-dimensional polyacrylamide gel electrophoresis following biosynthetic labeling of choroid plexus pieces with [14C]leucine in vitro. Approximately 20 major protein species were resolved which, with the exception of transferrin, transthyretin, and alpha 2-macroglobulin, appear to be unrelated to proteins found in high concentrations in plasma. Several patterns of developmental regulation were observed. At least two of the proteins were synthesized and secreted at high levels only by fetal choroid plexus, whereas the secretion of several other proteins including transferrin and proteins comigrating with cystatin C and alpha 2-macroglobulin increased only after birth. The levels of mRNA coding for transferrin, ceruloplasmin, cystatin C, alpha 2-macroglobulin, beta 2-microglobulin, and transthyretin were measured in the brain during development by dot hybridization and northern gel analysis. No mRNA was detected coding for the proteins alpha-fetoprotein, alpha 1-antitrypsin, haptoglobin, and thiostatin in the brain at any stage. For those proteins, which are produced in other parts of the brain as well as by the choroid plexus, the changes in their corresponding mRNA levels measured in whole brain paralleled the changes in their secretion by the choroid plexus. The results presented in this paper show that the choroid plexus is active in protein secretion at all stages studied. The changing pattern of protein secretion by the choroid plexus, combined with its early development compared with other tissues in the brain, suggests that it is active in providing the appropriate extracellular environment for the growth and differentiation of the brain.

Aging↗

Effects of the extracellular matrix on fetal choroid plexus epithelial cells: changes in morphology and multicellular organization do not affect gene expression.

We have developed a primary culture system for fetal mouse choroid plexus epithelial cells which maintains their differentiated phenotype. When grown on a reconstituted basement membrane substrate (Matrigel) epithelial cells formed aggregates which became embedded in the matrix and developed into characteristic and highly reproducible multicellular vesicular structures. These vesicles consisted of a squamous layer of epithelial cells with extensive attachment to the matrix substrate, surrounding a fluid-filled lumen. Electron microscopy showed that cells comprising these vesicles had a high degree of membrane specialization and polarized morphology which in many respects mimicked the in vivo morphology. Biochemical analyses demonstrated that under these culture conditions the tissue-specific pattern of gene expression of fetal choroid plexus epithelium was maintained. After 6 days in culture these cells contained approximately the same amount of transthyretin mRNA as the 12.5-day choroid plexus in vivo, and the level of total RNA per cell, which is proportional to the protein synthetic capability of the cells, was also maintained. The pattern of protein secretion was also very similar to that generated by fetal mouse choroid plexus cells in vivo. In contrast choroid plexus epithelial cells attached poorly to collagen I gels. Heterogeneous aggregates were formed in which cell-cell interactions were more extensive than cell-substrate interactions, and in no cases was a central lumen observed. Cells on the surface of large aggregates showed some evidence of membrane polarization, while the majority of cells in the cultures exhibited little evidence of polarized morphology. Despite the striking difference in morphology and multicellular organization these cells still expressed high levels of transthyretin mRNA and maintained the same pattern of protein synthesis as cells cultured on Matrigel. These results indicate that the basement membrane is important for the organization of choroid plexus epithelial cells into a functional epithelium in vitro and thus presumably the maintenance of the integrity of the blood-brain barrier in vivo. In contrast to several other epithelial systems which have been studied, the type of extracellular matrix does not appear to directly influence tissue-specific gene expression by choroid plexus epithelial cells. Thus the level of gene expression is not dependent on the cytoarchitecture and multicellular organization of this cell type.

Animals↗

Measurement of optic nerve blood flow with iodoantipyrine: limitations caused by diffusion from the choroid.

Radioactively labelled iodoantipyrine has been used to measure optic nerve blood flow in experimental animals. The reliability of blood flow measurements with this technique may be limited by diffusion of tracer from the nearby choroid. The activity of tracer in the peripapillary choroid and anterior optic nerve was measured in a series of in vivo optic nerve blood flow experiments in cats. The diffusion of iodoantipyrine into cat optic nerve segments was also measured in vitro, and a model for diffusion of tracer from the peripapillary choroid into the anterior optic nerve was developed. The activity profiles established by simple diffusion experiments were similar to the activity profiles in the anterior optic nerve established by blood flow experiments. Apparent blood flow measurements in the anterior optic nerve made with iodoantipyrine may be largely influenced by tracer diffusion from the nearby choroid. For measurements of tracer activity which are statistically similar between control and experimental optic nerve samples, and with a total diffusion time of 60 sec (a well-done experiment), real blood flow in the experimental sample may differ by as much as 60% from the control at a point 50 micron from the choroid. At 300 micron from the choroid, the maximum undetectable difference because of diffusion declines to approx. 12%. These estimates assume an autoradiographic technique which can reliably detect tissue tracer activity differences of +/- 10%. Measurements of optic nerve blood flow made with diffusible tracers are affected by diffusion from the choroid and should be reported with estimated limits of reliability.

Animals↗

Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid system.

The CSF is often regarded as merely a mechanical support for the brain, as well as an unspecific sink for waste products from the CNS. New methodology in receptor autoradiography, immunohistochemistry and molecular biology has revealed the presence of many different neuroendocrine substances or their corresponding receptors in the main CSF-forming structure, the choroid plexus. Both older research on the sympathetic nerves and recent studies of peptide neurotransmitters in the choroid plexus support a neurogenic regulation of choroid plexus CSF production and other transport functions. Among the endocrine substances present in blood and CSF, 5-HT, ANP, vasopressin and the IGFs have high receptor concentrations in the choroid plexus and have been shown to influence choroid plexus function. Finally, the choroid plexus produces the growth factor IGF-II and a number of transport proteins, most importantly transthyretin, that might regulate hormone transport from blood to brain. These studies suggest that the choroid plexus-CSF system could constitute an important pathway for neuroendocrine signalling in the brain, although clearcut evidence for such a role is still largely lacking.

Animals↗

Kinetic analysis of [36Cl]-, [22Na]- and [3H]mannitol uptake into the in vivo choroid plexus-cerebrospinal fluid brain system: ontogeny of the blood brain and blood-CSF barriers.

The kinetics of penetration of radioactive [36Cl]-, [22Na]- and [3H]mannitol into the choroid plexus-CSF brain system was investigated in 1-week, 2-week and adult Sprague-Dawley rats. For adult rats (5 weeks), 36Cl and 22Na uptake by the choroid plexus of lateral ventricle (LVCP) and fourth ventricle (4VCP) resolved into a fast component (t1/2 0.02 - 0.05 h) representing isotope distribution within the extracellular and residual erythrocyte compartments, and a slow component (t1/2 0.8 - 1.9 h) representing isotope movement into the epithelial cell compartment. From steady-state distribution data, choroid cell [Cl] in both LVCP and 4VCP was calculated to be 67 mmol/kg cell H2O, a level nearly 4 times greater than that predicted by the membrane potential for passive distribution. In 1-week immature rats cell [Cl] and [Na] in the choroid plexuses were even greater than the corresponding levels in adults, probably because ion transport across the basolateral membrane is not yet coupled with ion movement from cell to CSF. In mature rats the 36Cl and 22Na uptake into the CSF resolved into 2 components (t1/2 0.18 h, fractional volume 0.24 and t1/2 1.2 h, fractional volume 0.76); however, the fast component of CSF uptake, which likely represents isotope movement across the choroid plexuses, was negligible in the 1-week animals. Permeability-surface area products (PA) were determined for the blood-CSF barrier (i.e. the choroid plexuses) as well as the blood-brain barrier (cerebral cortex and cerebellum). The PA values for 36Cl and 22Na as determined by the fast component of CSF uptake (choroid plexus secretion?) were an order of magnitude less in the 1-week rats than in adults. In contrast, the effective permeability of the blood-CSF barrier as well as the blood-brain barrier, as evaluated by changes in PA of [3H]mannitol, decreased steadily with advancing age.

Age Factors↗

Transmission and scanning electron microscopic study of chlordecone (Kepone) induced changes in the male mouse choroid plexus.

To investigate the effects of the estrogenic insecticide chlordecone on the morphology of mouse choroid plexus, 4 different doses (100.0, 250.0, 500.0 and 1000.0 micrograms) of the chemical were administered intraperitoneally to groups of adult males. Concurrent with the chlordecone treatments, another group of males received 10.0 micrograms estradiol-17 beta; the control group was treated with sesame oil vehicle. After 15 days of daily chemical injections, the mice were terminated and the choroid plexus from fourth ventricle examined morphologically. Scanning (SEM) and transmission (TEM) electron microscopic examination of control choroid plexus showed the cuboidal epithelium profusely covered with microvilli. SEM examinations of choroid plexus epithelium after chlordecone treatments revealed dose-dependent, cell alterations that effected the microvilli and cell surfaces. After the highest chlordecone dose, microvilli were no longer visible, the choroidal cell membrane appeared either smooth or pitted and there was evidence of increased luminal debris. TEM observations of the same choroid plexus cells revealed vacuolated cytoplasm, dilated endoplasmic reticulum, vacuolated mitochondria with disrupted cristae and cellular degeneration. SEM and TEM examination of choroid plexus after estradiol treatments revealed similar cellular alterations to those recorded after chlordecone treatments. The possible significance of these data are discussed.

Animals↗

Polypoidal choroidal vasculopathy in tilted disk syndrome and high myopia with staphyloma.

PURPOSE: To describe polypoidal choroidal vasculopathy as a complication of tilted disk syndrome and high myopia with staphyloma. DESIGN: Retrospective interventional case series. METHODS: This report was a multicenter evaluation of six patients (eight eyes) with tilted disk syndrome or high myopia that was complicated by posterior staphyloma. Complete ophthalmic examination that included fluorescein angiography, optical coherence tomography (OCT), and indocyanine green angiography (ICG-A) was performed in all patients. RESULTS: All patients had macular abnormalities and visual loss. Fundus examination and fluorescein angiography showed typical features of tilted disk syndrome (five patients; six eyes) or high myopia (one patient; two eyes) with staphyloma that was associated with polypoidal choroidal vasculopathy. OCT and ICG-A confirmed the presence of polypoidal dilations in the choroid. Seven eyes were treated with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT), although one eye did not require treatment. Visual acuity at the final visit had improved in three eyes, deteriorated in three eyes, and remained unchanged in two eyes. CONCLUSION: Polypoidal choroidal vasculopathy is a potential cause of visual loss in tilted disk syndrome and high myopia. We postulate that choroidal abnormalities at the border of staphylomas induce blood-flow disturbances that are similar to those disturbances that are observed in chronic central serous chorioretinopathy, which is another condition that occasionally is associated with polypoidal choroidal vasculopathy. The pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conditions.

Aged↗