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PubMed1997

Functional characterization of choroid plexus epithelial cells in primary culture.

The objective of this study was to develop and evaluate a primary culture system for choroid plexus epithelial cells as an in vitro model for studying organic cation transport. Cells were dispersed from choroid plexus of neonatal rats by enzymatic digestion and grew as differentiated monolayers when plated on solid or permeable support. Electron microscopy showed that cultured cells were morphologically similar to intact choroid plexus epithelium, having apical tight junctions between cells, numerous mitochondria, basal nuclei and apical microvilli and cilia. As previously demonstrated for intact choroid plexus, immunocytochemistry showed that Na+,K+-ATPase was localized to the apical membrane, and GLUT-1, the facilitative glucose transporter, was localized to the basolateral membrane of cultured cells. Apical transport of L-proline by cultured cells was mediated by a sodium-dependent, electrogenic process, as in whole tissue. 14C-Tetraethylammonium (TEA), a prototypic organic cation, was accumulated by isolated choroid plexus in a time-dependent manner; uptake was inhibited by tetrapentylammonium (TePA). In cultured cells, apical TEA transport was mediated by a saturable process coupled to cellular metabolism. Unlabeled TEA and other organic cations (TePA, N1-methylnicotinamide and mepiperphenidol) inhibited TEA transport; the organic anion, p-aminohippurate, had no effect. Finally, TePA-sensitive transport of 14C-TEA was stimulated after preloading the cells with unlabeled TEA. Based on the morphological, biochemical and functional properties of these cultured cells, we conclude that this primary culture system should be an excellent in vitro model for experimental characterization of choroid plexus function.

Animals↗
PubMed1997

[Analysis of choroidal blood flow by laser speckle flowgraphy].

We applied real-time laser speckle flowgraphy (RLSFG) to quantitate the choroidal circulation. RLSFG was developed utilizing the laser speckle phenomenon. A diode laser, 830 nm in wavelength, serves as the light source. The quantitative index of blood flow velocity is represented as normalized blur (NB), or square blur rate (SBR). This method was applied to the posterior fundus of monkey and human eyes. While one measurement covers a fundus area of 1 mm x 1 mm, it is possible to measure a wider fundus area by montage. The wide color maps showed the architecture of choroidal vessels. It was possible to measure the choroidal blood flow in areas free of major retinal vessels. Application of the method to 3 eyes of retinal artery occlusion and 4 eyes of geographic choroiditis showed that the obtained SBR values in normal fundus is derived 25% from the retinal and 75% from the choroidal circulation. The findings show the potential value of RLSFG in quantitating the choroidal blood flow in situ.

Animals↗
PubMed1997

Immunohistochemical expression of S-100 beta in choroidal melanomas.

OBJECTIVE: To investigate the expressivity of S-100 beta antibodies in choroidal melanomas and to compare it with that of S-100 protein and HMB-45. DESIGN: Twenty-seven choroidal melanoma specimens obtained from the McGill University Ophthalmic Pathology Registry were classified as spindle cell, epithelioid cell or mixed-cell type. Immunohistochemistry was performed using the standard peroxidase-antiperoxidase technique with monoclonal HMB-45, polyclonal S-100, polyclonal S-100 beta and monoclonal S-100 alpha beta antibodies in formalin-fixed, paraffin-embedded sections. OUTCOME MEASURE: Intensity of immunoreaction. The result was considered positive when at least five focal areas of stained cells were observed within the tumour. RESULTS: All 27 tumours were positive for HMB-45, 19 (70%) for S-100, 23 (85%) for S-100 beta, and 21 (78%) for S-100 alpha beta. No correlation was found between the intensity of the immunoreaction and cell classification. CONCLUSIONS: HMB-45 is the most reliable marker for choroidal melanomas. S-100 beta is a more sensitive marker than S-100 for choroidal melanomas regardless of cell type. Contrary to previous reports, S-100 beta should not be considered a useful immunomarker to differentiate between primary choroidal melanoma and cutaneous melanoma metastatic to the choroid.

Antibodies, Monoclonal↗
PubMed1998

Foveolar choroidal blood flow in age-related macular degeneration.

PURPOSE: To compare measurements of the foveolar choroidal blood circulation in subjects with nonexudative, age-related macular degeneration (AMD) with those of control subjects. METHODS: Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the center of the fovea. Measurements were obtained in 20 eyes of 20 subjects with 10 or more large drusen, visual acuity of 20/32 or better, and no evidence of choroidal neovascularization. Findings obtained in these subjects were compared with those of 10 eyes of 10 age- and blood pressure-matched control subjects with no large drusen. Foveolar choroidal blood flow measurements were obtained by asking the study participants to fixate on a probing laser beam. RESULTS: No significant differences in average age, blood pressure, or intraocular pressure were observed between subjects with AMD and control subjects. In subjects with AMD, average ChBVol was 0.24 +/- 0.08 (+/- 1 SD) arbitrary units (AU); this value was 33% lower than that of control subjects (0.36 +/- 0.11 AU; two-tailed, independent Student's t-test, P = 0.005). Average ChBVel, conversely, was not significantly different from normal (0.44 +/- 0.07 AU) in subjects with AMD (0.44 +/- 0.10 AU). Average ChBFlow in subjects with AMD (8.7 +/- 3.1 AU) was 37% lower than that of control subjects (13.7 +/- 3.5 AU) (P = 0.0005). Average blood flow pulsatility was 6% higher in subjects with AMD (0.71 +/- 0.15) than in control subjects (0.66 +/- 0.14), but this difference was not statistically significant (P = 0.42). CONCLUSIONS: Average ChBFlow in the nonexudative stages of AMD is lower than that of age-matched controls, and the effect is caused mainly by a decrease in ChBVol. Further studies are needed to elucidate whether decreased ChBFlow plays a role in the development of choroidal neovascularization, and whether ChBFlow measurements may help identify subjects with AMD at risk for developing choroidal neovascularization.

Aged↗
PubMed1999

Optical coherence tomography of idiopathic polypoidal choroidal vasculopathy.

PURPOSE: To document and study the cross-sectional structures of polypoidal elements using optical coherence tomography in eyes with idiopathic polypoidal choroidal vasculopathy. METHODS: Optical coherence tomography images of two eyes with idiopathic polypoidal choroidal vasculopathy were correlated with slit-lamp biomicroscopic findings, fundus photographs, fluorescein angiograms, and indocyanine green angiograms. RESULTS: Cross-sectional optical coherence tomographic images of retinochoroidal structures showed prominent anterior protrusion of the orange subretinal mass corresponding to the polypoidal structure in the indocyanine green angiogram. Hemorrhagic detachment of the retinal pigment epithelium was contiguous with the cone-shaped nodule beneath the retinal pigment epithelium in one eye, and an apparent discontinuity was observed in the highly reflective layer that delineates the polypoidal structure. CONCLUSIONS: Some of the polypoidal structures in eyes with idiopathic polypoidal choroidal vasculopathy are anteriorly protruding lesions in the inner choroid that may cause serosanguineous detachment of the retinal pigment epithelium through damage of the overlying Bruch membrane, retinal pigment epithelium, and the adhesion between them. Cross-sectional optical coherence tomographic images may increase understanding of the pathophysiology of idiopathic polypoidal choroidal vasculopathy.

Aged↗
PubMed2006

The distribution of the anti-HIV drug, tenofovir (PMPA), into the brain, CSF and choroid plexuses.

BACKGROUND: Tenofovir disoproxil fumarate, a prodrug of the nucleotide reverse transcriptase inhibitor, tenofovir (9-[9(R)-2-(phosphonomethoxy)propyl]adenine; PMPA), was recently approved for use in the combination therapy of human immunodeficiency virus (HIV)-1 infection. This study was undertaken to understand PMPA distribution to the virus sanctuary sites located in the brain, CSF and choroid plexuses and to clarify its possible role in reducing the neurological problems associated with HIV infection. METHODS: The methods used included an established bilateral carotid artery perfusion of [3H]PMPA and a vascular marker, D-[14C]mannitol, in anaesthetised guinea-pigs followed by scintillation counting, HPLC and capillary depletion analyses. Movement of [3H]PMPA into the brain, cisternal CSF and lateral ventricle choroid plexus was also examined in the absence and presence of additional anti-HIV drugs and a transport inhibitor. Control and test groups were compared by ANOVA or Student's t-test, as appropriate. RESULTS: The distribution of [3H]PMPA in the cerebrum, cerebellum, pituitary gland and cerebral capillary endothelial cells was not significantly different to that measured for D-[14C]mannitol. However, [3H]PMPA accumulation was significantly higher than that of D-[14C]mannitol in the choroid plexus and CSF. Further experiments revealed no cross-competition for transport of [3H]PMPA by probenecid, a non-specific inhibitor of organic anion transport, or the nucleoside reverse transcriptase inhibitors into any of the CNS regions studied. The octanol-saline partition coefficient measurement for [3H]PMPA was 0.0134 +/- 0.00003, which is higher that the 0.002 +/- 0.0004 measured for D-[14C]mannitol in an earlier study. CONCLUSION: There is negligible transport of [3H]PMPA across the blood-brain barrier, but it can cross the blood-CSF barrier. This is a reflection of the differing physiological and functional characteristics of the blood-CNS interfaces. Self- and cross-inhibition studies did not suggest the involvement of a transport system in the CNS distribution of this drug. However, the ability of PMPA to accumulate in the choroid plexus tissue, but not the cerebral capillary endothelial cells, and the hydrophilic nature of PMPA, does point to the possibility of a transporter at the level of the choroid plexus. PMPA that has crossed the choroid plexus and is in the CSF could treat HIV-infected perivascular and meningeal macrophages, but it is unlikely to reach the infected microglia of deep brain sites.

Journal Article↗
PubMed1996

Choroid plexus papilloma of the cerebellopontine angle.

Choroid plexus papillomas are rare tumors, representing less than 1% of all intracranial neoplasms in our review of the English literature. Derived from the neuroepithelial cells of the choroid plexus, these tumors recapitulate the structure of the normal choroid plexus, often demonstrating a well-developed papillary architecture. This tumor most commonly affects children and typically arises in the lateral ventricles. Before 1992, 26 cases have been reported arising in the cerebellopontine angle. We describe an example of choroid plexus papilloma of the cerebellopontine angle that was initially diagnosed as metastatic papillary carcinoma. A metastatic disease workup revealed a right thyroid lobe nodule. Fine needle aspiration biopsy of this nodule yielded a few atypical cells, but no evidence of papillary carcinoma. We performed additional laboratory investigations to rule out the possibility of a primary papillary carcinoma of the thyroid gland and to make a definitive diagnosis of a choroid plexus papilloma. This article reviews choroid plexus papilloma of the cerebellopontine angle and demonstrates the use of immunohistochemistry to differentiate this benign primary neoplasm from well-differentiated metastatic papillary carcinoma.

Adult↗
PubMed2004

Inhibition of choroidal neovascularization by a peptide inhibitor of the urokinase plasminogen activator and receptor system in a mouse model.

OBJECTIVES: To determine the role played by the urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) system in choroidal neovascularization (CNV) and whether inhibition of this system can suppress the extent of CNV in an animal model. METHODS: Choroidal neovascularization was induced in mice by laser photocoagulation using the slitlamp delivery system. Reverse transcriptase-polymerase chain reaction and immunocytochemical analysis were performed on the retina choroids of these animals to examine the expression of uPAR. For 2 weeks following laser treatment, animals were injected intraperitoneally with a novel peptide inhibitor of the uPA-uPAR system (100 mg/kg twice a day every day, every other day, and once a week). Control laser-treated animals receive an intraperitoneal injection of phosphate-buffered saline every day. Following treatment, animals were perfused with fluorescein-labeled dextran, eyes were removed, and the areas of new vessels were examined in the retina-choroid whole mounts by fluorescence microscopy and quantitated using image analysis software. RESULTS: In this study, uPAR was found to be up-regulated in the choroidal tissues of mice with laser-induced CNV. The uPAR was localized to the endothelial cells of the fibrovascular tissue within the CNV complex. Systemic administration of the peptide inhibitor of the uPA-uPAR system resulted in a significant reduction of CNV (up to 94%). The response was found to be frequency-of-dose dependent. No toxic effects or tissue destruction was noted following the peptide treatment. CONCLUSIONS: Our results strongly suggest that up-regulation of the uPA-uPAR system is an important step during CNV, and significant inhibition of CNV was seen when cell surface-associated uPA-uPAR activity was prevented with the peptide inhibitor. Clinical Relevance Inhibition of the protease system (uPA-uPAR) may prove to be a potential novel antiangiogenic therapy for CNV as seen in age-related macular degeneration.

Animals↗
PubMed1997

Unifocal helioid choroiditis.

OBJECTIVE: To report a previously undescribed clinical entity involving an unusual inflammatory lesion of the choroid. PATIENTS: Six young, healthy patients experienced acute unilateral visual loss secondary to unifocal choroiditis in the macula. RESULTS: All patients exhibited a solitary, elevated, yellow-white active focus of choroiditis with overlying subretinal fluid and in some cases subretinal hemorrhaging. The lesions were approximately 1 disc diameter in size and, on follow-up, showed minimal growth, then gradual resolution of the subretinal fluid. No other signs of ocular inflammation were noted, except in 1 patient who had anterior chamber and vitreous inflammation. In the 3 patients with prolonged follow-up, elevated white plaquelike lesions persisted with little change over time. Relapses were seen, and some permanent visual loss occurred in 1 of the 3 patients. Systemic evaluations revealed no definitive etiology. CONCLUSIONS: To our knowledge, these patients exhibit an undescribed clinical entity, separable from previously established choroidal disorders. The cause of the lesions remains uncertain. We call this entity "unifocal helioid choroiditis."

Adolescent↗
PubMed2004

Plasticity of polypoidal lesions in polypoidal choroidal vasculopathy.

PURPOSE: The aim of this study was to describe the clinical course in a patient with polypoidal choroidal vasculopathy (PCV). METHODS: A 68-year-old man with PCV in the left eye was followed up by means of routine examinations including fluorescein angiography and indocyanine green angiography for over 60 months. RESULTS: Throughout the follow-up period, the patient experienced repeated lesions in the macula, such as serosanguineous detachment of the retinal pigment epithelium and neurosensory retina, but retained good visual acuity. Indocyanine green angiography disclosed spontaneous regression of polypoidal vessels followed by significant changes in the choroidal circulation: a group of polypoidal structures disappeared, and after several months a small choroidal vessel became apparent that was distant from the previously observed polypoidal structure rather than representing an extension of the original lesion. CONCLUSION: The clinical observation suggests that in some cases of PCV the choroidal vasculature may be altered with time, in that some vessels in the inner choroid and even the choriocapillaris may close and collateral vessels and/or new vessels may develop to form complex such as that described here.

Aged↗
PubMed2006

Isolated choroidal melanocytosis: a distinct clinical entity?

PURPOSE: The objective was to describe a distinct, limited form of congenital ocular melanocytosis that involves the choroid only. METHODS: A retrospective descriptive case series study of 11 patients with similar appearing broad-based but entirely flat melanotic choroidal lesions was carried out. RESULTS: All 11 lesions were homogeneously dark brown in color with at least one striated margin. They were located in various regions of the fundus from the macula and juxtapapillary area to the periphery. They ranged in size from 6 to 23 mm in the largest basal diameter, but all 11 were completely flat. The youngest patient was only 2 months old when the lesion was first detected, but the oldest was 82 years old. None of the 7 lesions that were re-evaluated over a median follow-up of 4 years enlarged or changed appreciably otherwise. CONCLUSIONS: The choroidal lesions described in this report may be a distinct, limited form of congenital ocular melanocytosis. We refer to these lesions as "isolated choroidal melanocytosis." Lesions of this type may predispose affected patients to choroidal melanoma.

Adolescent↗
PubMed1998

Detection of choroidal aneurysms with indocyanine green videoangiography.

BACKGROUND: Aneurysms of the choroidal vasculature have been described only in histopathological studies. METHODS: Indocyanine green videoangiograms obtained with the scanning laser ophthalmoscope from 32 patients with geographic atrophy were reviewed. RESULTS: In 8 of 32 patients indocyanine green videoangiography (ICGVA) showed hyperfluorescent aneurysms along choroidal arteries. The same aneurysmal formations were found in two of the eight patients on very early images of fluorescein videoangiography before dye leakage occurred. Seven of eight patients with choroidal aneurysms had a history of hypertension. CONCLUSIONS: ICGVA is a useful diagnostic tool in detecting choroidal aneurysms. Multiple mechanisms are probably involved in the pathogenesis of choroidal aneurysms, among them the higher hemodynamic stress in the macular region, hypertension and aging.

Aged↗
PubMed2005

Gender and estrogen supplementation increases severity of experimental choroidal neovascularization.

Observational clinical studies suggest that post-menopausal women may be at risk for more severe age-related macular degeneration, and that estrogen loss due to menopause may contribute. We sought to determine the effect of gender and estrogen status on the severity of choroidal neovascularization (CNV) in a mouse model for experimental choroidal neovascularization. Laser-induced CNV was performed in mice with or without estrogen supplementation. At various times, eyes were removed for analysis of severity of CNV lesions or for extraction of choroidal mRNA to evaluate iNOS, TNF-alpha, MMP-9, and ER-alpha expression, which are molecules relevant to angiogenic processes. Also, splenic macrophages were analysed for iNOS to determine the effect of estrogen treatment in vitro. Finally, laser-induced CNV was performed in iNOS -/- mice. Our result showed that aged female mice had significantly larger CNV than age-matched males. Ovariectomy in adult mice did not increase severity, but paradoxically estrogen supplementation after ovariectomy did increase CNV severity. More severe CNV were associated with a significant decrease in choroidal iNOS mRNA. Splenic macrophages from estrogen supplemented mice showed a significant increased in TNF-alpha mRNA expression (eight fold difference compared to the control) but only a mild change in iNOS mRNA levels (2-3 fold difference). In vitro data further showed that nitric oxide production in splenic macrophages at different estrogen levels was not different from controls. Finally, CNV severity was significantly more severe in iNOS -/- mice, compared to iNOS +/+ mice after laser treatment. In conclusion, aged female mice developed more severe CNV than do males. Estrogen replacement seems to increase severity, possibly by suppressing the upregulation of choroidal iNOS and activating macrophages. The putative beneficial or detrimental role of estrogen biology in age-related macular degeneration must be more carefully evaluated and may vary with the stage of age-related macular degeneration (atrophic or neovascular) as well as with the specific target cell type (monocytes vs. endothelial cell or vascular smooth muscle cell).

Aging↗
PubMed2001

Initial experience of inferior limited macular translocation for subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration.

PURPOSE: To report our initial experience of inferior limited macular translocation in patients with subfoveal choroidal neovascularization resulting from causes other than age-related macular degeneration. METHODS: We conducted a retrospective study of 23 eyes of 22 patients with choroidal neovascularization involving the foveal center secondary to pathologic myopia (11 eyes), ocular histoplasmosis syndrome (four eyes), angioid streaks (four eyes), idiopathic neovascularization (three eyes), and multifocal choroiditis (one eye), in which the fovea was moved inferiorly by means of limited macular translocation surgery. The mean preoperative best-corrected visual acuity was 20/150, and in five of 23 eyes (21.7%) the visual acuity was 20/80 or better. The major outcome measures were preoperative and postoperative visual acuity, postoperative foveal displacement, and complications related to the surgery. RESULTS: The mean postoperative follow-up was 10.82 months (range, 6 to 18 months). Postoperative best-corrected visual acuity improved by 2 or more Snellen lines of visual acuity in 11 of 23 eyes (47.82%), remained within 1 line in seven of 23 eyes (30.43%), and worsened 2 or more lines of vision in five of 23 eyes (21.74%). The mean postoperative best-corrected visual acuity was 20/100, and in 12 of the 23 eyes (52.17%) the visual acuity achieved was 20/80 or better. Retinal detachment was the most frequent complication and occurred in six eyes (26%). CONCLUSIONS: Our initial experience with limited macular translocation shows that this treatment modality offers the potential to improve visual function in some eyes with subfoveal choroidal neovascularization secondary to myopia, ocular histoplasmosis syndrome, angioid streaks, idiopathic neovascularization, and multifocal choroiditis. Although longer and more complete follow-up is needed, the results of this initial series warrant further studies to define the precise role of macular translocation in the management of these conditions.

Adult↗
PubMed2002

Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration.

PURPOSE: To report angiographic observations about feeder vessel identification after photodynamic therapy in patients with choroidal neovascularization caused by age-related macular degeneration. DESIGN: Cohort study. METHODS: We analyzed fluorescein and indocyanine green dynamic angiography in 156 eyes of 145 patients before and after photodynamic therapy to identify the feeder vessels of the choroidal neovascular membrane. RESULTS: Before photodynamic therapy one or more feeder vessel could be detected in 35 (22.4%) out of 156 eyes with choroidal neovascularization. Three months after photodynamic therapy, a feeder vessel could be identified in 112 (84.2%) out of 133 eyes with persistent choroidal neovascularization. Among these, 16 eyes received direct laser photocoagulation of the feeder vessel and did not need any further photodynamic therapy. CONCLUSION: Previous photodynamic therapy improves the detection of the feeder vessel of the choroidal neovascularization. A sequential combined therapy (photodynamic and feeder vessel treatment) could be considered as an alternative to multiple photodynamic treatments.

Choroid↗
PubMed2002

Atypical choroidal neovascularization in radiation retinopathy.

PURPOSE: To report atypical choroidal neovascularization associated with radiation retinopathy. DESIGN: Case report. METHODS: The patient was examined with ophthalmoscopy, fluorescein angiography, and indocyanine green angiography. RESULTS: A 32-year-old woman presented with an accelerated course of radiation retinopathy with macular edema, capillary telangiectasis, subretinal fluid, and lipid during and after pregnancy. Indocyanine green, but not fluorescein angiography, demonstrated an unusual area of choroidal neovascularization with prominent saccular dilations adjacent to a large zone of poor choroidal perfusion. Laser photocoagulation of the choroidal neovascularization resulted in an angiographic closure with absorption of the subretinal fluid and improvement of visual acuity. CONCLUSIONS: Choroidal neovascularization may be associated with radiation retinopathy and, when present, may require indocyanine green angiography for its diagnosis.

Adult↗
PubMed2002

Selection for inferior limited macular translocation on the basis of distance from the fovea to the inferior edge of the subfoveal choroidal neovascularization.

PURPOSE: To assess the visual outcome of inferior limited macular translocation in eyes selected based on the distance from the fovea to the inferior edge of the subfoveal choroidal neovascularization. DESIGN: Interventional case series. METHODS: We performed inferior limited macular translocation in 12 consecutive eyes (12 patients) with age-related macular degeneration or polypoidal choroidal vasculopathy, in which the choroidal neovascularization did not extend for more than half of one disk diameter inferior to the fovea. RESULTS: In all eyes, the choroidal neovascularization was moved to an extrafoveal location. In seven of the 12 eyes, postoperative vision was 20/40 or better. The visual acuity improved by 2 or more lines in 11 eyes. CONCLUSION: Selection for inferior limited macular translocation on the basis of distance from the fovea to the inferior edge of the choroidal neovascularization may be associated with a greater likelihood of visual acuity improvement.

Aged↗
PubMed1996

Focal posttraumatic choroidal granulomatous inflammation.

PURPOSE: This study was performed to describe the clinicopathologic features of a group of patients with posttraumatic unilateral focal choroidal granulomatous inflammation. METHODS: Enucleated eyes with focal choroidal granulomatous inflammation without clinical signs of contralateral ocular inflammation were identified. Clinical and pathologic features were recorded. RESULTS: Six enucleated eyes that had been injured by projectiles had focal uveal granulomatous inflammation of the posterior choroid. Four eyes had uvea attached to or incarcerated into the wound. Two eyes had foreign material associated with the granulomatous inflammation, and two eyes had a disrupted lens with lens-induced inflammation. Two eyes exhibited the focal granulomatous inflammation at the site of a choroidal rupture. None of the six enucleated eyes contained Dalen-Fuchs' nodules. CONCLUSIONS: Focal choroidal granulomatous inflammation may occur as a result of penetrating ocular trauma. The origin of this condition is unknown, although it likely represents a reaction to a foreign body.

Adolescent↗