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Carnosine uptake in rat choroid plexus primary cell cultures and choroid plexus whole tissue from PEPT2 null mice.

PEPT2 is functionally active and localized to the apical membrane of rat choroid plexus epithelial cells. However, little is known about the transport mechanisms of endogenous neuropeptides in choroid plexus, and the role of PEPT2 in this process. In the present study, we examined the uptake kinetics of carnosine in rat choroid plexus primary cell cultures and choroid plexus whole tissue from wild-type (PEPT2(+/+)) and null (PEPT2(-/-)) mice. Our results indicate that carnosine is preferentially taken up from the apical as opposed to basolateral membrane of cell monolayers, and that basolateral efflux in limited. Transepithelial flux of carnosine was not distinguishable from that of paracellular diffusion. The apical uptake of carnosine was characterized by a high affinity (K(m) = 34 microM), low capacity (V(max) = 73 pmol/mg protein/min) process, consistent with that of PEPT2. The non-saturable component was small (K(d) = 0.063 microL/mg protein/min) and, under linear conditions, was only 3% of the total uptake. Studies in transgenic mice clearly demonstrated that PEPT2 was responsible for over 90% of carnosine's uptake in choroid plexus whole tissue. These findings elucidate the unique role of PEPT2 in regulating neuropeptide homeostasis at the blood-cerebrospinal fluid interface.

Amino Acids↗

Metastasis of choroidal melanoma to the contralateral choroid, orbit, and eyelid.

A 52-year-old woman was found to have a small juxtapapillary pigmented lesion in the choroid of the left eye. This lesion remained clinically stationary for one year, but subsequent growth prompted enucleation of the eye. The tumour was diagnosed histologically as a choroidal malignant melanoma of mixed cell type. Approximately 52 months later the patient developed proptosis of the contralateral (right) eye. Orbital ultrasonography showed a large mass in the right orbit, which was confirmed by needle biopsy to be a melanoma. In addition the patient was found to have metastatic melanoma to the choroid, right lower eyelid area, and liver. The development of simultaneous orbital, choroidal, and eyelid metastases from a contralateral choroidal melanoma is of ophthalmic interest and appears to be unique.

Choroid Neoplasms↗

Photodynamic therapy and indocyanine green guided feeder vessel photocoagulation of choroidal neovascularization secondary to choroid rupture after blunt trauma.

PURPOSE: To describe photodynamic therapy (PDT) and additional indocyanine green (ICG) guided feeder vessel photocoagulation as a treatment of choroidal neovascularization (CNV) secondary to choroidal rupture in case of blunt head trauma. DESIGN: Interventional case report. METHODS: A 61-year-old woman developed subfoveal CNV originating from a choroid tear 8 years after blunt head trauma. Four sessions of PDT were applied and an additional two consecutive sessions of selective ICG-guided feeder vessel photocoagulation conducted. RESULTS: Transient reduction of leakage and closure of feeder vessels could not prevent further growth of the CNV. CONCLUSIONS: PDT reduced leakage temporarily and additional ICG-guided feeder vessel photocoagulation closed treated feeder vessel and CNV. New feeder vessel formation and growth of CNV in case of traumatic choroid rupture could not be treated effectively by these two laser treatment modalities to prevent severe deterioration of visual acuity.

Choroid↗

Malignant melanoma of the choroid associated with spontaneous expulsive choroidal hemorrhage.

A 79-year-old man initially had a perforated corneal ulcer of his blind right eye. The next day a spontaneous expulsive choroidal hemorrhage occurred just before scheduled enucleation. Histopathologic examination of the enucleated eye revealed a severe necrosis of several posterior ciliary arteries in the expulsive choroidal hemorrhage, as well as a large occult spindle B malignant melanoma of the choroid. The necrosis of the posterior ciliary arteries may have been the cause of the choroidal hemorrhage. The finding of an occult malignant melanoma may be more than a chance occurrence of two unrelated events, inasmuch as both are associated with necrosis of the posterior ciliary arteries.

Aged↗

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization associated with multifocal choroiditis.

PURPOSE: Evaluation of visual acuity outcomes of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis. DESIGN: Open-label, prospective, interventional case series. METHODS: Thirteen patients (13 eyes) diagnosed with subfoveal CNV associated with multifocal choroiditis at the Eye Clinics of Trieste and Udine were considered for the study. Inclusion criteria were the presence of subfoveal CNV no larger than 5,400 microm in greatest linear dimension and best-corrected visual acuity, Snellen equivalent, of approximately 20/400 or better. The primary outcome was the number of eyes that had fewer than 8 letters lost (less than approximately 1.5 lines) at the 12-month examination compared with the baseline examination. Secondary outcomes included fluorescein angiographic features such as progression and CNV size. RESULTS: Baseline and final best-corrected visual acuity were 0.52 logarithm of the minimal angle of resolution (20/62(-2) Snellen equivalent) and 0.55 logarithm of the minimal angle of resolution (20/62(-2) Snellen equivalent), respectively. By the 12-month visit, one patient (7.7%) had gained at least 1.5 lines, two patients (15.4%) had lost 1.5 or more lines, and no patient lost 3 or more lines of visual acuity, whereas 10 patients (84.6%) showed less than 1.5-line change. Mean CNV area was 0,69 mm(2) and 0.63 mm(2) at baseline and at the 12-month visit, respectively. By the month 12 examination, patients had received an average of 1.7 treatments. CONCLUSIONS: Photodynamic therapy may be considered a viable therapeutic option for subfoveal CNV associated with multifocal choroiditis at least for a 1-year period. Further studies with longer follow-up are needed to confirm these results.

Adult↗

Photodynamic therapy in young patients with choroidal neovascularization following traumatic choroidal rupture.

PURPOSE: To assesses the role of photodynamic therapy (PDT) with verteporfin in young patients with choroidal neovascularization (CNV) secondary to traumatic choroidal rupture. DESIGN: Retrospective case series. METHODS: Of 26 eyes with traumatic choroidal rupture followed since 1984 at the retina service of university hospitals, all eyes diagnosed with CNV and treated with PDT were included. Medical records including comprehensive eye examination, retinal photography, and intravenous fluorescein angiography (IVFA) were studied. RESULTS: Five patients (mean age, 18 years) developed CNV and received an average of two PDT treatments. Three patients had improved visual acuity (VA), one remained stable, and one experienced visual loss. Final IVFA showed absence of leakage in four eyes and decreased leakage in the eye with decreased VA. CONCLUSIONS: In young patients, PDT may be a reasonable treatment for CNV secondary to choroidal rupture. No ocular or systemic PDT complications were encountered in this young population.

Adolescent↗

[Sub-choroidal implanted Greene melanoma: an animal experiment model for malignant choroid melanoma].

A modified technique for subchoroidal transplantation of amelanotic Greene melanoma cells and the intraocular growth patterns of this tumor in rabbit eyes are described. Tumor fragments were implanted via a scleral tunnel in 71 rabbit eyes, with 64 successful tumor growths, producing a prominent, circumscribed choroidal mass within 12-14 days of surgery. Choroidal Greene melanoma in rabbits resembles human epithelioid uveal melanoma in both its growth patterns and morphologic characteristics. The authors' implantation technique guarantees reliable growth of choroidal tumors with easily reproducible size and location. The experimental choroidal melanoma model is particularly valuable in clinical studies where a large number of tumors, with limited variation, is necessary for different experimental groups.

Animals↗

Choroid plexus epithelium (normal and neoplastic) expresses synaptophysin. A potentially useful aid in differentiating carcinoma of the choroid plexus from metastatic papillary carcinomas.

As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin.

Adolescent↗

Idiopathic polypoidal choroidal vasculopathy (IPCV) presenting with simultaneous choroidal neovascular membrane (CNM).

Idiopathic polypoidal choroidal vasculopathy (IPCV), a rare retinal condition initially described in 1982, is characterized by retinal pigment epithelial (RPE) detachments associated with choroidal polypoidals. Although it is recognized as a unique entity, many consider it a peculiar representation of choroidal neovascular membrane (CNM), commonly associated with age-related macular degeneration (ARMD). We report a case of IPCV with simultaneous presentation of CNM. Dilated examination and fluorescein angiography (FA) revealed RPE detachments associated with choroidal polypoidals. FA also revealed a lacy hyperfluorescent vascular lesion. Ocular manifestations, differential diagnoses, and treatment options are discussed, with emphasis on similarities and differences between IPCV and CNM. It is imperative to consider IPCV in the differential diagnosis of RPE detachments, including those associated with CNM. Careful funduscopic evaluation, FA, and/or indocyanine green videoangiography analysis helps confirm the diagnosis.

Adult↗

Clinicopathologic findings in a patient with serpiginous choroiditis and treated choroidal neovascularization.

We present the ocular clinicopathologic features of the left eye of a patient who, during a 29-year period, developed the characteristic features of progressive serpiginous choroiditis. Two areas of choroidal neovascularization were successfully treated by laser photocoagulation. The larger area of neovascularization, located in and inferior to the maculopapillary bundle area and treated with argon laser, resulted in a scar composed of hyperplastic retinal pigment with persistence of neovascularization and full-thickness destruction of the retina. A smaller area of neovascularization, located temporal to the fovea and treated by krypton laser, resulted in a fibrous scar with obliteration of the new vessels and preservation of the inner retinal layers. A diffuse and focal infiltrate of lymphocytes was present in the choroid. Often, larger aggregates of lymphocytes were present at the margin of the serpiginous lesions. The serpiginous lesions were characterized by loss of retinal pigment epithelium and the photoreceptor cell layer. The margins of most lesions had variable degrees of hyperplastic retinal pigment epithelium and some had defects in Bruch's membrane, through which fibroglial scar tissue extended into the choroid.

Choroid↗

Choroidal (subretinal) neovascularization secondary to choroidal nevus and successful treatment with argon laser photocoagulation. Case reports and review of literature.

Retinal detachment secondary to choroidal nevus may be caused by subretinal fluid accumulation or neovascularization. Foveal subretinal fluid or leakage of choroidal neovascularization may impair visual acuity. 10 cases of nevus with serous sensory retinal detachment successfully treated with laser photocoagulation are reviewed. 2 additional cases of successful laser therapy for retinal detachment secondary to choroidal neovascularization with nevus of the choroid are presented.

Choroid↗

Soluble EphB4 regulates choroidal endothelial cell function and inhibits laser-induced choroidal neovascularization.

PURPOSE: The purpose of this study was to evaluate the effect of a soluble monomeric form of the EphB4 extracellular domain (sEphB4) on choroidal endothelial cell (CEC) migration and tube formation and on experimental laser-induced choroidal neovascularization (CNV). METHODS: EphrinB2 and EphB4 expression in CECs was investigated by Western blot analysis and immunohistochemistry. Effects of sEphB4 (0.5-3 microg/mL) on CEC migration were evaluated with a modified Boyden chamber assay. Tube formation was assayed in CEC cultures in collagen gel. CNV was induced in rats by laser photocoagulation. The effects of intravitreal injection of sEphB4 on CNV development were evaluated at day 14 by fluorescein angiography (FA), confocal volumetric analysis of isolectin-B4 labeled flatmounts, and histologic examination of CNV membranes. RESULTS: CEC cells express both EphB4 and EphrinB2, according to Western blot analysis. Immunohistochemical sections of rat eye showed immunoreactivity for both EphB4 and EphrinB2 in the choroidal endothelium. sEphB4 reduced CEC migration in response to vascular endothelial growth factor (P < 0.01). Similarly, sEphB4 inhibited CEC tube formation in a dose-dependent manner. EphB4, and to a lesser extent EphrinB2, were detected on vascular channels within laser-induced CNV membranes. Intravitreal injection of sEphB4 inhibited laser-induced CNV formation. CNV membranes showed a reduction in leakage score (P < 0.05), and membrane volumes were reduced in size (P < 0.05). Histologic analysis revealed that vascularity was reduced in sEphB4-treated membranes. CONCLUSIONS: Recombinant soluble monomeric EphB4 exerts an inhibitory effect on choroidal angiogenesis in vitro and in vivo. It should be further evaluated for its potential as a novel therapy for CNV.

Animals↗

Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment.

PURPOSE: To study the long-term effects of photodynamic therapy (PDT), using liposomal benzoporphyrin derivative (BPD) or Verteporfin, on experimental choroidal neovascularization (CNV) and on normal retina and choroid (with no CNV) in the cynomolgus monkey eye. METHODS: Photodynamic therapy was performed in 8 cynomolgus monkey eyes with experimental CNV induced by laser injury. The effect of PDT on normal retina and choroid (with no CNV) was studied in 9 monkey eyes. Liposomal BPD was administered intravenously (0.375 mg/kg) either as a bolus, as a slow infusion over 32 minutes, or as a fast infusion over 10 minutes. Photodynamic therapy was performed using light at a wavelength of 689 or 692 nm, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2. Follow-up studies, including fundus photography and FA, were performed at 24 hours after PDT and then weekly. Indocyanine green and BPD angiography were performed in selected cases. Tissues were examined with light and electron microscopy at the end of follow-up. RESULTS: Twenty-three of the 32 areas of CNV treated with PDT showed absence of angiographic leakage at 24 hours. Twenty-eight areas of CNV were followed for 4 weeks; 22 of 28 showed absence of angiographic leakage at 2 weeks; and 20 of 28 at 4 weeks of follow-up. Forty spots on the normal retina and choroid were treated with PDT and were followed for 4 to 7 weeks. These spots showed pigment-laden cells in the outer retina, variably pigmented retinal pigment epithelium (RPE) in the treated area, intact neurosensory retina, and reperfusion of the choriocapillaris. CONCLUSIONS: Photodynamic therapy leads to absence of angiographic leakage for at least 4 weeks in experimental CNV in the monkey model. In the normal monkey eye the RPE and choriocapillaris show generalized recovery with preservation of the neurosensory retina 7 weeks after PDT.

Animals↗

Choroidal vascular aneurysm with massive choroidal hemorrhage.

A rare case of a choroidal vascular aneurysm arising from the short posterior ciliary artery is reported in a 40-year-old woman. The aneurysm was detected by fluorescein angiography. It caused recurrent choroidal hemorrhage with blindness as the outcome. The diagnosis of aneurysm would have been missed without fluorescein angiography. A search should be made for choroidal vascular aneurysm in cases of spontaneous choroidal and vitreous hemorrhage both clinically (using fluorescein angiography) and histopathologically (in the event of enucleation of the eyeball).

Adult↗

[Carboxyamido-triazole inhibits substeps of choroidal neovascularization on retinal pigment epithelial cells and choroidal endothelial cells in vitro].

BACKGROUND: Retinal pigment epithelial cells (RPE cells) and choroidal endothelial cells (CECs) are important cell types in the process of choroidal neovascularization in exudative age-related macular degeneration (AMD). In this study, we evaluated the antiproliferative and antimigratory abilities of carboxyamido-triazole (CAI), a drug modulating calcium-dependent signal transduction on RPE cells and CECs. METHODS: Human fetal RPE cells and bovine CECs were exposed to CAI in a concentration range of 0.1 to 10 microM. Cell proliferation was stimulated with 10% serum or 10 ng/ml bFGF. The effect of CAIs on cell proliferation was estimated. Furthermore, we evaluated CAI's effects on CEC and RPE cell migration induced by fibronectin. RESULTS: CAI had a stronger inhibitory effect on serum-induced CEC proliferation than on RPE cell proliferation. A much stronger effect was seen on the proliferation of bFGF-stimulated RPE cells and CECs. Furthermore, the fibronectin-stimulated migration of RPE cells and CECs was inhibited by CAI. In this assay, a stronger inhibitory effect was seen on RPE cells than on CECs. CONCLUSION; CAI inhibits important substeps of choroidal neovascularization on RPR cells and CECs. Therefore, CAI may be of value for the treatment of choroidal neovascularization in exudative AMD.

Antineoplastic Agents↗

Intrinsic choroidal neurons in the duck eye receive sympathetic input: anatomical evidence for adrenergic modulation of nitrergic functions in the choroid.

Intrinsic choroidal neurons (ICN) in the duck eye form an intramural ganglionic plexus that may subserve complex integrative functions. A key feature of such ganglia is an innervation by sympathetic postganglionic neurons. The present study was thus aimed at determining the sympathetic postganglionic innervation of ICN. Choroids were processed for double immunofluorescence labelling with the following markers: tyrosine-hydroxylase (TH)/nitric oxide synthase (nNOS), TH/galanin (GAL), dopamine-beta-hydroxylase (DBH)/vasoactive intestinal polypeptide (VIP), TH/DBH and DBH/alpha-smooth-muscle actin (alphaSMA), and for triple immunofluorescence labelling with VIP/DBH/TH. Epifluorescence and confocal laser scanning microscopy were used for evaluation. Immunoperoxidase staining for TH or DBH in combination with NADPH-diaphorase histochemistry was applied for electron microscopy. ICN spread over the entire choroid but were concentrated in an equatorial zone passing obliquely from naso-cranial to temporocaudal. More than 80% of nNOS-positive ICN showed close appositions of TH/DBH-immunoreactive varicose nerve fibres at the light-microscopic level, as could be confirmed by confocal laser scanning microscopy. Ultrastructurally, these appositions could be defined as both synapses or close contacts without synaptic specialisation. Vascular and non-vascular smooth muscle fibres also received TH/DBH-immunopositive innervation. Our findings suggest that most ICN receive a sympathetic input that might modulate their nitrergic effects upon vascular and non-vascular smooth muscle fibres in the choroid and that they may have more complex functions than merely being a simple parasympathetic relay.

Actins↗

Differential diagnosis of diffuse choroidal atrophies. Diffuse choriocapillaris atrophy, choroideremia, and gyrate atrophy of the choroid and retina.

Three young children showed a similar fundus appearance of sharply defined, yellowish-white, patchy or geographic atrophy of the retina and choroid and visible large choroidal vessels in almost the entire fundus. Fluorescein angiography disclosed atrophy of the retinal pigment epithelium and loss of choriocapillaris. Their visual functions and electrophysiologic findings were also similar. Family A was diagnosed as having diffuse choriocapillaris atrophy with autosomal dominant inheritance; family B, choroideremia with X-linked recessive heredity; and family C, gyrate atrophy of the choroid and retina with hyperornithinemia and autosomal recessive transmission. It became evident that diffuse choriocapillaris atrophy, choroideremia, and gyrate atrophy sometimes show a similar fundus appearance. Fluorescein angiography, serum ornithine levels, and family history were particularly helpful to differentiate these diffuse choroidal atrophies.

Adolescent↗

Melanosis of the choroid plexus, ependyma, subependymal neuroglia, and dentate and trigeminal motor nuclei: observations on the choroidal and ependymal cilia.

Melanosis of the choroid plexus, ependyma, subependymal neuroglia of the fourth ventricle, and dentate and trigeminal motor nuclei was found in a 50-year-old man who died with cor pulmonale, hypertensive cardiovascular disease, and intracerebral hemorrhage. This case is the first known example of melanosis not associated with neurocutaneous melanosis to involve multiple structures of the brain. Nonenzymatic conversion of lipofuscin into melanin is suggested as the mechanism of the melanosis. Cilia of the choroidal epithelium and ependyma were identified in this case, despite a long delay in postmortem examination. These observations on choroidal epithelium confirm previous reports that the choroid plexus of man is ciliated, as in other mammals and lower vertebrates.

Brain Diseases, Metabolic↗