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Sample records for active choroidal lesions

  1. Indocyanine green angiography-guided management of Vogt-Koyanagi-Harada disease: differentiation between choroidal scars and active lesions.

    PubMed

    Knecht, Pascal B; Mantovani, Alessandro; Herbort, Carl P

    2013-10-01

    . HDDs in this case were interpreted as stromal choroidal scars. ICGA-guided therapy (mainly HDD evolution monitoring) helps to eradicate occult stromal disease in VKH and avoids 'sunset glow' fundus, by allowing precise adjustment of therapy. In some cases, HDDs do not represent active lesions but presumed intrastromal scars which need to be identified. A limited course of maximal IST including PIM can unmask such cases and avoid overtreatment of these patients. PMID:23277207

  2. Fundus Autofluorescence and Optical Coherence Tomography Findings in Choroidal Melanocytic Lesions

    PubMed Central

    Materin, Miguel A.; Raducu, Raluca; Bianciotto, Carlos; Shields, Carol L.

    2010-01-01

    Purpose: To establish the characteristics of secondary retinal and retinal pigment epithelial (RPE) changes associated with the presence of choroidal melanoma and choroidal nevus as documented by optical coherence tomography (OCT) and fundus autofluorescence (FAF). Materials and Methods: PubMed review of major English publications examining the correlation between clinical characteristics of choroidal melanoma and nevus with OCT and FAF findings. Results: The intrinsic properties of choroidal melanoma, as well as overlying RPE changes, drusen, and lipofuscin are best characterized by FAF, while OCT is more sensitive for the identification of subretinal and intraretinal fluid as well as atrophy, degeneration, and photoreceptor loss in the neurosensory retina. Conclusions: Secondary retinal changes associated with choroidal melanocytic lesions can be documented by OCT and FAF. OCT-evident changes are observed more often with choroidal melanoma than choroidal nevus. OCT is better suited to identify the overlying retinal detachment and edema, even before these findings are clinically apparent. FAF is most useful in documenting the presence of lipofuscin, a finding that represents one of the important criteria in differentiating small choroidal melanoma from benign choroidal nevus. PMID:20844674

  3. In Vivo Choroidal Vascular Lesions in Diabetes on Swept-Source Optical Coherence Tomography.

    PubMed

    Murakami, Tomoaki; Uji, Akihito; Suzuma, Kiyoshi; Dodo, Yoko; Yoshitake, Shin; Ghashut, Rima; Yoza, Rina; Fujimoto, Masahiro; Yoshimura, Nagahisa

    2016-01-01

    Diabetes induces microvascular diseases including diabetic retinopathy and choroidopathy which reciprocally promote the pathogenesis, although optical coherence tomography images of diabetic choroidopathy remains to be documented. Here we evaluated the qualitative characteristics of choroidal vascular lesions in patients with diabetes and their association with diabetic retinopathy on swept-source optical coherence tomography (SS-OCT) images. We retrospectively reviewed 110 consecutive eyes of 110 patients with diabetes and 35 eyes of 35 healthy subjects for whom SS-OCT images (6x6-mm scans centered on the fovea) of sufficient quality were acquired. The curve of chorioretinal sections was flattened using Bruch's membrane as a reference surface, followed by generation of en-face images. We characterized choroidal vascular lesions and evaluated their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA), retinal and choroidal thicknesses, and diabetic retinopathy severity. En-face SS-OCT images showed unvisualized vessels in Sattler's layer in 33 eyes (30.0%). Focal narrowing was seen in choroidal vessels in Haller's layer in 56 eyes (50.9%). The choroidal vessels ended in the superficial or middle portion of Haller's layer, referred to as vascular stumps, in 20 eyes (18.2%). Diabetic eyes had these findings more frequently than nondiabetic eyes. The subfoveal choroid was thicker in eyes with focal vascular narrowing and vascular stumps than in eyes without such lesions. Vascular stumps in Haller's layer were significantly related to diabetic retinopathy severity, logMAR VA, and central retinal and choroidal thicknesses. These novel findings on SS-OCT images would promote the better understanding of complicated pathogenesis in diabetic retinopathy and choroidopathy. PMID:27479070

  4. In Vivo Choroidal Vascular Lesions in Diabetes on Swept-Source Optical Coherence Tomography

    PubMed Central

    Murakami, Tomoaki; Uji, Akihito; Suzuma, Kiyoshi; Dodo, Yoko; Yoshitake, Shin; Ghashut, Rima; Yoza, Rina; Fujimoto, Masahiro; Yoshimura, Nagahisa

    2016-01-01

    Diabetes induces microvascular diseases including diabetic retinopathy and choroidopathy which reciprocally promote the pathogenesis, although optical coherence tomography images of diabetic choroidopathy remains to be documented. Here we evaluated the qualitative characteristics of choroidal vascular lesions in patients with diabetes and their association with diabetic retinopathy on swept-source optical coherence tomography (SS-OCT) images. We retrospectively reviewed 110 consecutive eyes of 110 patients with diabetes and 35 eyes of 35 healthy subjects for whom SS-OCT images (6x6-mm scans centered on the fovea) of sufficient quality were acquired. The curve of chorioretinal sections was flattened using Bruch’s membrane as a reference surface, followed by generation of en-face images. We characterized choroidal vascular lesions and evaluated their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA), retinal and choroidal thicknesses, and diabetic retinopathy severity. En-face SS-OCT images showed unvisualized vessels in Sattler’s layer in 33 eyes (30.0%). Focal narrowing was seen in choroidal vessels in Haller’s layer in 56 eyes (50.9%). The choroidal vessels ended in the superficial or middle portion of Haller’s layer, referred to as vascular stumps, in 20 eyes (18.2%). Diabetic eyes had these findings more frequently than nondiabetic eyes. The subfoveal choroid was thicker in eyes with focal vascular narrowing and vascular stumps than in eyes without such lesions. Vascular stumps in Haller’s layer were significantly related to diabetic retinopathy severity, logMAR VA, and central retinal and choroidal thicknesses. These novel findings on SS-OCT images would promote the better understanding of complicated pathogenesis in diabetic retinopathy and choroidopathy. PMID:27479070

  5. Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Clarkson, Donna R.; Valo, Lynn M.; Brown, Jeremiah, Jr.; Stuck, Bruce E.

    2003-06-01

    Purpose: To determine funduscopic criteria that will help predict when bridging choroidal neovascular (CNV) complexes will develop after laser retinal trauma and to define early preventive treatment targets. Methods: Ten rhesus monkeys were used and retinal lesions were produced by Nd:YAG exposures (20ns, 1-2mJ, 1064nm, min. spot size) simulating human accidental laser trauma to the central fundus. Funduscopy and fluorescein/ICG angiography were conducted at day 1, 4, and 14, and at 2 and 4 months, and animals terminated for histologic evaluation. Predisposition for bridging fibrovascular complexes was evaluated for single lesions, two small lesions showing coalescing hemorrhages, and multiple lesions involved with large field subretinal and vitreous hemorrhages. Results: Elevated CNVs were present in all single lesions with confined subretinal hemorrhages. All lesion sets that showed initial and small coalescing subretinal hemorrhages formed bridging CNV scars. No bridging CNVs occurred in lesion sets involving a vitreous hemorrhage adjacent to a confined, but small subretinal hemorrhage. In large field subretinal hemorrhages involving multiple laser lesions, complex CNV formation occurred. Extensive secondary photoreceptor losses occurred in confined hemorrhage and CNV zones. Conclusion: Trauma presenting with evidence of coalescing and confined subretinal hemorrhages between two adjacent lesions has a high chance of forming choroidal neovascular bridge complexes between the involved lesions. CNV formation may be related to the long residence time, break down products, and clearance processes of extravasated blood. Removal of trapped blood and curtailing angiogenesis and cellular proliferation may be helpful treatment strategies.

  6. Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal Neovascularization In Vivo

    PubMed Central

    McCloskey, Manabu; Wang, Haibo; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Hartnett, M. Elizabeth

    2013-01-01

    Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV) model of macular degeneration, Rap1b−/− mice exhibited larger CNV volumes compared to wild-type or Rap1a−/−. In vivo, intravitreal injection of a cAMP analog (8CPT-2′-O-Me-cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2′O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2′-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo with 8

  7. A Case of Ampiginous Choroiditis

    PubMed Central

    Lambrecht, Pieter; Claeys, Marnix; De Schryver, Ilse

    2015-01-01

    Purpose Presentation of a case report of a unilateral ampiginous choroiditis. Methods This is an observational case report. Results A 70-year-old woman was referred to us with unilateral scattered chorioretinal lesions. The multifocal pattern of the lesions and the angiographic features led to the diagnosis of ampiginous choroiditis. Conclusion Ampiginous choroiditis is a primary inflammatory choriocapillaropathy with characteristics of both acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis. PMID:26955348

  8. Classification of choroiditis based on inflammatory lesion process rather than fundus appearance: enhanced comprehension through the ICGA concepts of the iceberg and jellyfish effects.

    PubMed

    Herbort, C P; Papadia, M; Mantovani, A

    2012-04-01

    Choroidal inflammatory diseases have been classically grouped under the term of white dot syndromes (WDS), a term only based on the appearance (white-yellow dots) of inflammatory fundus lesions. This purely descriptive and vague terminology, regrouping a pot-pourri of posterior inflammatory conditions, probably came into use because the precise exploration of the choroid was not possible, and also because many of the diseases were rare and not well understood. Since the availability of indocyanine green angiography (ICGA) that allows one to explore the choroidal compartment, it became possible to understand the lesion mechanism of choroiditides and to classify this group of diseases according to their pathophysiological behaviour. It was our aim to show here that the term WDS is applied to and encompasses inflammatory conditions that are characterized by completely different lesion mechanisms and should therefore be classified separately from each other. ICGA made it possible to differentiate two types of choroiditides, including on the one hand inflammatory diseases of the choroidal stroma and on the other hand inflammatory diseases of the choriocapillaris. Unfortunately, twenty years after its advent, ICGA is still not used routinely in uveitis centres and the traditional inappropriate but overall useless term of WDS is still used, maintaining the confusion about these diseases. The aim of this work was (i) to illustrate that meaningful exploration of choroidal inflammation, mostly occult and inaccessible to usual investigations, has to be performed using ICGA, (ii) to insist on the crucial importance of ICGA in the management of choroiditis and (iii) to enhance the comprehension of the ICGA-based classification of choroiditis, by using the demonstrative and striking analogue concepts of iceberg and jellyfish effects. PMID:22495994

  9. A critical role for pannexin-1 in activation of innate immune cells of the choroid plexus

    PubMed Central

    Maslieieva, Valentyna; Thompson, Roger J

    2014-01-01

    Epiplexus cells are a population of innate immune cells in the choroid plexus of the brain ventricles. They are thought to contribute to the immune component of the blood-cerebrospinal-fluid-barrier (BCSFB). Here we have developed a novel technique for studying epiplexus cells in acutely isolated, live and intact choroid plexus. We show that epiplexus cells are potently activated by exogenous ATP, increasing their motility within the tissue. This ATP-induced chemokinesis required activation of pannexin-1 channels, which are expressed by the epithelial cells of the choroid plexus and not the epiplexus cells themselves. Furthermore, ATP acts at least in part through the P2X4 ionotropic purinergic receptor. Thus, the resident immune cells of the choroid plexus appear to be in communication with the epithelial cells through pannexin-1 channels. PMID:24418937

  10. Choroid Plexus

    MedlinePlus

    ... spread widely via the cerebrospinal fluid. Choroid plexus papilloma is a rare, benign (noncancerous) tumor. Choroid plexus ... the malignant (cancerous) form of the choroid plexus papilloma. Choroid plexus carcinoma occurs primarily in children. Location ...

  11. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    PubMed Central

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  12. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion.

    PubMed

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-04-28

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  13. Polypoidal choroidal vasculopathy.

    PubMed

    Ciardella, Antonio P; Donsoff, Irene M; Huang, Sheau J; Costa, Danielle L; Yannuzzi, Lawrence A

    2004-01-01

    Polypoidal choroidal vasculopathy was first described as a peculiar hemorrhagic disorder of the macula, characterized by recurrent sub-retinal and sub-retinal pigment epithelium bleeding in middle aged black women. The use of indocyanine green angiography and subsequently of optical coherent tomography has widened our ability to study and understand the pathophysiology of this disorder. The primary abnormality involves the choroidal circulation, and the characteristic lesion is an inner choroidal vascular network of vessels ending in an aneurysmal bulge or outward projection, visible clinically as a reddish orange, spheroid, polyp-like structure. We have also recognized that individuals of African-American and Asian descents are more at risk for developing polypoidal choroidal vasculopathy as the disorder seems to preferentially affect pigmented individuals. However, it has been shown that while that still holds true, patients of other racial backgrounds may be afflicted. Particularly, polypoidal choroidal vasculopathy has been found to be present in about 8-13% of white patients with clinical appearance of exudative age-related macular degeneration. Polypoidal choroidal vasculopathy has also been reported in Irish, French, German, and Italian patients. The natural course of the disease often follows a remitting-relapsing course, and clinically, it is associated with chronic, multiple, recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina with long-term preservation of good vision. Photodynamic treatment appears to be a promising alternative to conventional laser therapy, for the treatment of polypoidal choroidal vasculopathy. In conclusion, polypoidal choroidal vasculopathy seems to be a distinct clinical entity that should be differentiated from other types of choroidal neovascularization associated with age-related macular degeneration and other known choroidal degenerative, inflammatory, and ischemic disorders. PMID

  14. Unique challenges faced by pediatric neurosurgeon Harvey Cushing in 1909 at Johns Hopkins: a choroid plexus tumor of the lateral ventricle mimicking a cerebellar lesion

    PubMed Central

    Pendleton, Courtney; Olivi, Alessandro; Jallo, George I.

    2015-01-01

    Introduction At the turn of the twentieth century, diagnosis of pediatric intracranial lesions frequently relied exclusively on the subtle, nonspecific signs associated with these pathologies. In absence of detailed neuroimaging, erroneous diagnoses and misdirected operative explorations were common within pediatric populations. Methods Following institutional review board approval, and through the courtesy of the Alan Mason Chesney Archives, we reviewed the surgical files from the Johns Hopkins Hospital for the years 1896–1912. Harvey Cushing's neurosurgical cases were collected and further analyzed. Results A 9-year-old boy presented with a year-long history of headaches and blindness. His neurological examination was remarkable for focal cranial nerve deficits and cerebellar signs. Cushing diagnosed a cerebellar tumor with hydrocephalus and performed two suboccipital explorations with negative results. The patient died prior to further operative intervention, and the postmortem examination revealed a large choroid plexus tumor within the left lateral ventricle. Conclusions Early neurosurgical diagnosis and operative planning was fraught with difficulties, and surgeons relied solely on history and physical examination for localization of intracranial lesions. Here we report a case of a choroid plexus tumor of the lateral ventricle, which was misdiagnosed by Cushing. This case serves to emphasize the unique challenges faced by pediatric neurosurgeons at the turn of the twentieth century, who relied solely on history and examination to localize intracranial lesions. PMID:21494884

  15. Circumscribed Choroidal Hemangioma

    PubMed Central

    Karimi, Saeed; Nourinia, Ramin; Mashayekhi, Arman

    2015-01-01

    Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities. PMID:26730320

  16. Lead Exposure Promotes Translocation of Protein Kinase C Activities in Rat Choroid Plexus in Vitro, but Not in Vivo

    PubMed Central

    Zhao, Qiuqu; Slavkovich, Vesna; Zheng, Wei

    2016-01-01

    Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial preparations, which may underlie Pb-induced damage at the blood–brain barrier. Our previous work indicates that Pb accumulates in the choroid plexus and causes dysfunction of this blood–cerebrospinal fluid (CSF) barrier. The present studies were undertaken to test the hypothesis that Pb in the choroid plexus may alter PKC activity and thus affect the functions of the blood–CSF barrier. When choroidal epithelial cells in a primary culture were exposed to Pb (10 μM in culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the cytosolic PKC activities decreased, an indication of the induction of PKC translocation by Pb. The effect of Pb on cellular PKC was concentration dependent in the range of 0.1–10 μM. We further evaluated PKC activity of the choroid plexus in rats chronically exposed to Pb in the drinking water (control, 50 or 250 μg Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance revealed a significant age-related decline of PKC activities in both cytosol and membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC activities. In addition, we found that short-term, acute Pb exposure in rats did not significantly change PKC activities nor did it affect the expression of PKC isoenzymes in the choroid plexus. Our results suggest that Pb exposure may promote the translocation of PKC from cytosol to membrane in rat blood–CSF barrier in vitro, but not in vivo. PMID:9512732

  17. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  18. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  19. Choroidal OCT

    NASA Astrophysics Data System (ADS)

    Esmaeelpour, Marieh; Drexler, Wolfgang

    Novel imaging devices, imaging strategies and automated image analysis with optical coherence tomography have improved our understanding of the choroid in health and pathology. Non-invasive in-vivo high resolution choroidal imaging has had its highest impact in the investigation of macular diseases such as diabetes macular edema and age-related macular degeneration. Choroidal thickness may provide a clinically feasible measure of disease stage and treatment success. It will even support disease diagnosis and phenotyping as is demonstrated in this chapter. Utilizing color coded thickness mapping of the choroid and its Sattler's and Haller's layer may further strengthen the sensitivity of the investigation findings.

  20. Doxycycline-mediated Inhibition of Choroidal Neovascularization

    PubMed Central

    Samtani, S.; Amaral, J.; Campos, M.; Fariss, R. N.; Becerra, S. P.

    2010-01-01

    Purpose Doxycycline, a broad spectrum antibiotic, has certain anti-angiogenic properties and can inhibit matrix metalloproteinases (MMPs/gelatinases). We investigated the effects of doxycycline on choroidal neovascularization (CNV), and regulation of MMP-2/-9 and pigment epithelium-derived factor (PEDF). Methods Doxycycline was orally administered to rats at 500, 50, 5, and 0.5 mg/kg/day, using non-treated animals as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At seven days post-induction, animals were euthanized, and eyes collected. RPE/choroid flat-mounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and Volocity® software. MMP-2, MMP-9 and PEDF protein levels were determined by ELISA. MMP catalytic activity was determined in solution using fluorogenic gelatin and peptide substrates, by gelatin zymography in SDS-PAGE and by in situ DQ-gelatin zymography in RPE/choroid sections. Results CNV complex lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/day caused a 70% inhibition of CNV complex volume compared to control animals. Doxycycline elevated PEDF levels in plasma, and did not affect the plasma pro- and active MMP-2 and MMP-9 levels. However, the in vitro enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline. MMP-2, MMP-9 and gelatinolytic activities in situ increased early in CNV lesion development. Doxycycline treatments and exogenous additions inhibited gelatinolytic activities in CNV lesions. Conclusions Doxycycline effectively hampered the progression of experimental CNV. The results suggest that orally administrated doxycycline can reach the choroid to attenuate proteolytic enzymes that remodel Bruch's membrane and promote the anti-angiogenic PEDF to inhibit neovascularization. PMID:19516001

  1. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization

    PubMed Central

    Wang, Haibo; Jiang, Yanchao; Shi, Dallas; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Wittchen, Erika S.; Li, Dean Y.; Hartnett, M. Elizabeth

    2014-01-01

    Activation of Rap1 GTPase can improve the integrity of the barrier of the retina pigment epithelium (RPE) and reduce choroidal neovascularization (CNV). Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1 inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a murine model of laser-induced CNV, we determined that reduced Rap1 activity in RPE/choroid occurred with CNV formation and that activation of Rap1 by 2′-O-Me-cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS. In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE barrier integrity via cadherin phosphorylation and facilitated choroidal EC migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b−/− mice reduced laser-induced CNV, in correlation with decreased ROS generation in RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier.—Wang, H., Jiang, Y., Shi, D., Quilliam, L. A., Chrzanowska-Wodnicka, M., Wittchen, E. S., Li, D. Y., Hartnett, M. E. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization. PMID:24043260

  2. Retinal and choroidal TGF-beta in the tree shrew model of myopia: isoform expression, activation and effects on function.

    PubMed

    Jobling, Andrew Ian; Wan, Ran; Gentle, Alex; Bui, Bang Viet; McBrien, Neville Anthony

    2009-03-01

    A visually evoked signalling cascade, which begins in the retina, transverses the choroid, and mediates scleral remodelling, is considered to control eye growth. The ubiquitous cytokine TGF-beta has been associated with alterations in ocular growth, where alterations in scleral TGF-beta isoforms mediate the scleral remodelling that results in myopia. However, while the TGF-beta isoforms have been implicated in the scleral change during myopia development, it is unclear whether alterations in retinal and choroidal isoforms constitute part of the retinoscleral cascade. This study characterised the retinal and choroidal TGF-beta isoform profiles and TGF-beta2 activation during different stages of myopia development, as induced by form deprivation, in a mammalian model of eye growth. Using quantitative real-time PCR, the mRNA for all three mammalian isoforms of TGF-beta was detected in tree shrew retina and choroid. Distinct tissue-specific isoform profiles were observed for the retina (TGF-beta1:TGF-beta2:TGF-beta3=20:2085:1) and choroid (TGF-beta1:TGF-beta2:TGF-beta3=16:23:1), which remained constant over the development period under investigation. The active and latent pools of retinal TGF-beta2 were quantified using ELISA with the majority (>94%) of total TGF-beta2 found in the latent form. Unlike previous scleral data showing early and continuous decreases in TGF-beta isoform expression during myopia development, the levels of the three isoforms remained within normal ranges for retinal (TGF-beta1, -14 to +14%; TGF-beta2, -2 to +20%; TGF-beta3, -10 to +26%) and choroidal (TGF-beta1, -19 to +21%; TGF-beta2, -26 to +8%; TGF-beta3, -11 to +28%) tissues during myopia development (induction times of 3h, 7h, 11h, 24h, and 5 days). A 40% decrease in retinal TGF-beta2 activation was observed after 5 days of myopia development, however, there was no functional correlate of altered TGF-beta2 activity, as assessed by the retinal ERG response. Overall, these data highlight

  3. Choroidal Blood-Flow Responses to Hyperoxia and Hypercapnia in Men with Obstructive Sleep Apnea

    PubMed Central

    Tonini, Matthieu; Khayi, Hafid; Pepin, Jean-Louis; Renard, Elisabeth; Baguet, Jean-Philippe; Lévy, Patrick; Romanet, Jean-Paul; Geiser, Martial H.; Chiquet, Christophe

    2010-01-01

    Study Objectives: Obstructive sleep apnea (OSA) impacts on macrovasculature and autonomic function and may therefore interfere with ocular microvascular regulation. We hypothesized that choroidal vascular reactivity to hyperoxia and hypercapnia was altered in patients with OSA compared with matched control subjects and would improve after treatment with continuous positive airway pressure (CPAP). Methods: Sixteen healthy men were matched 1:1 for body mass index, sex, and age with 16 men with newly diagnosed OSA without comorbidities. Subjects underwent sleep studies, 24-hour blood pressure monitoring, arterial stiffness measurements, and cardiac and carotid echography. Overall, patients were middle-aged, lean, and otherwise healthy except for having OSA with a limited amount of desaturation, with, at most, subclinical lesions of the cardiovascular system, stage 1 hypertension, or both. Choroidal laser Doppler flowmetry provides a unique opportunity to assess microvascular function by measuring velocity, (ChBVel), volume (ChBVol), and relative subfoveal choroidal blood flow (ChBF). Vascular choroidal reactivity was studied during hyperoxia and hypercapnia (8% CO2) challenges before and after treatment with nasal CPAP. Results: Patients with OSA and control subjects exhibited similar choroidal reactivity during hyperoxia (stability of choroidal blood flow) and hypercapnia (significant increases in ChBVel of 13.5% and in ChBF of 16%). Choroidal vasoreactivity to CO2 was positively associated with arterial stiffness in patients with OSA. Gas choroidal vasoreactivity was unchanged after 6 to 9 months of CPAP treatment. Conclusion: This study showed unimpaired choroidal vascular reactivity in otherwise healthy men with OSA. This suggests that patients with OSA, without comorbidities, have long-term adaptive mechanisms active in ocular microcirculation. Citation: Tonini M; Khayi H; Pepin JL; Renard E; Baguet JP; Lévy P; Romanet JP; Geiser MH; Chiquet C. Choroidal blood

  4. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 108 viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  5. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  6. Choroidal melanoma

    PubMed Central

    Singh, Parul; Singh, Abhishek

    2012-01-01

    Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma. PMID:22557869

  7. Functional demonstration of Na+-K+-2Cl- cotransporter activity in isolated, polarized choroid plexus cells.

    PubMed

    Wu, Q; Delpire, E; Hebert, S C; Strange, K

    1998-12-01

    The function of the apical Na+-K+-2Cl- cotransporter in mammalian choroid plexus (CP) is uncertain and controversial. To investigate cotransporter function, we developed a novel dissociated rat CP cell preparation in which single, isolated cells maintain normal polarized morphology. Immunofluorescence demonstrated that in isolated cells the Na+-K+-ATPase, Na+-K+-2Cl- cotransporter, and aquaporin 1 water channel remained localized to the brush border, whereas the Cl-/HCO-3 (anion) exchanger type 2 was confined to the basolateral membrane. We utilized video-enhanced microscopy and cell volume measurement techniques to investigate cotransporter function. Application of 100 microM bumetanide caused CP cells to shrink rapidly. Elevation of extracellular K+ from 3 to 6 or 25 mM caused CP cells to swell 18 and 33%, respectively. Swelling was blocked completely by Na+ removal or by addition of 100 microM bumetanide. Exposure of CP cells to 5 mM BaCl2 induced rapid swelling that was inhibited by 100 microM bumetanide. We conclude that the CP cotransporter is constitutively active and propose that it functions in series with Ba2+-sensitive K+ channels to reabsorb K+ from cerebrospinal fluid to blood. PMID:9843718

  8. Active removal of inorganic phosphate from cerebrospinal fluid by the choroid plexus.

    PubMed

    Guerreiro, Pedro M; Bataille, Amy M; Parker, Sonda L; Renfro, J Larry

    2014-06-01

    The P(i) concentration of mammalian cerebrospinal fluid (CSF) is about one-half that of plasma, a phenomenon also shown here in the spiny dogfish, Squalus acanthias. The objective of the present study was to characterize the possible role of the choroid plexus (CP) in determining CSF P(i) concentration. The large sheet-like fourth CP of the shark was mounted in Ussing chambers where unidirectional (33)P(i) fluxes revealed potent active transport from CSF to the blood side under short-circuited conditions. The flux ratio was 8:1 with an average transepithelial resistance of 87 ± 17.9 Ω·cm(2) and electrical potential difference of +0.9 ± 0.17 mV (CSF side positive). Active P(i) absorption from CSF was inhibited by 10 mM arsenate, 0.2 mM ouabain, Na(+)-free medium, and increasing the K(+) concentration from 5 to 100 mM. Li(+) stimulated transport twofold compared with Na(+)-free medium. Phosphonoformic acid (1 mM) had no effect on active P(i) transport. RT-PCR revealed both P(i) transporter (PiT)1 and PiT2 (SLC20 family) gene expression, but no Na(+)-P(i) cotransporter II (SLC34 family) expression, in the shark CP. PiT2 immunoreactivity was shown by immunoblot analysis and localized by immunohistochemistry in (or near) the CP apical microvillar membranes of both the shark and rat. PiT1 appeared to be localized primarily to vascular endothelial cells. Taken together, these data indicate that the CP actively removes P(i) from CSF. This process has transport properties consistent with a PiT2, Na(+)-dependent transporter that is located in the apical region of the CP epithelium. PMID:24740787

  9. Fibrosis of the Choroid Plexus Filtration Membrane

    PubMed Central

    Parratt, John D. E.; Kirwan, Paul D.

    2016-01-01

    We report a previously undescribed inflammatory lesion consisting of deposition of activated complement (C3d and C9neo) in association with major histocompatibility complex type II (MHC2)-positive activated microglia in choroid plexus villi exhibiting classical fibrous thickening of the pericapillary filtration membrane. The proportion of villi affected ranged from 5% to 90% in 56 adult subjects with diseases of the CNS and 11 subjects with no preexisting disease of the CNS. In 3 of the 4 children studied, 2% or less of examined villi showed stromal thickening, complement deposition, and the presence of MHC2-positive microglia; in adults, the proportion of villi affected increased with age. Other features of the lesion included loss of capillaries and failure by macrophages to clear extracellular particulate electron-dense material by clathrin-mediated phagocytosis. This choroid plexus lesion may relate pathogenetically to age-related macular degeneration and to Alzheimer disease, 2 other conditions with no known risk factors other than increasing age. All 3 conditions are characterized by the presence of damaged capillaries, inflammatory extracellular aggregates of mixed molecular composition and defective clearance of the deposits by macrophages. PMID:27444353

  10. Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo

    PubMed Central

    Li, Tao; Aredo, Bogale; Zhang, Kaiyan; Zhong, Xin; Pulido, Jose S.; Wang, Shusheng; He, Yu-Guang; Huang, Xianming; Brekken, Rolf A.; Ufret-Vincenty, Rafael L.

    2015-01-01

    Purpose Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. Methods Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. Results We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. Conclusions We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV. PMID:26529048

  11. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography

    PubMed Central

    Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  12. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography.

    PubMed

    Lee, Hoyoung; Bae, Kunho; Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  13. Cd59a deficiency in mice leads to preferential innate immune activation in the retinal pigment epithelium-choroid with age.

    PubMed

    Herrmann, Philipp; Cowing, Jill A; Cristante, Enrico; Liyanage, Sidath E; Ribeiro, Joana; Duran, Yanai; Abelleira Hervas, Laura; Carvalho, Livia S; Bainbridge, James W B; Luhmann, Ulrich F O; Ali, Robin R

    2015-09-01

    Dysregulation of the complement system has been implicated in the pathogenesis of age-related macular degeneration. To investigate consequences of altered complement regulation in the eye with age, we examined Cd59a complement regulator deficient (Cd59a(-/-)) mice between 4 and 15 months. In vivo imaging revealed an increased age-related accumulation of autofluorescent spots in Cd59a(-/-) mice, a feature that reflects accumulation of subretinal macrophages and/or microglia. Despite this activation of myeloid cells in the eye, Cd59a(-/-) mice showed normal retinal histology and function as well as normal choroidal microvasculature. With age, they revealed increased expression of activators of the alternative complement pathway (C3, Cfb, Cfd), in particular in the retinal pigment epithelium (RPE)-choroid but less in the retina. This molecular response was not altered by moderately-enhanced light exposure. Cd59a deficiency therefore leads to a preferential age-related dysregulation of the complement system in the RPE-choroid, that alone or in combination with light as a trigger, is not sufficient to cause choroidal vascular changes or retinal degeneration and dysfunction. This data emphasizes the particular vulnerability of the RPE-choroidal complex to dysregulation of the alternative complement pathway during aging. PMID:26234657

  14. Endogenous endostatin inhibits choroidal neovascularization.

    PubMed

    Marneros, Alexander G; She, Haicheng; Zambarakji, Hadi; Hashizume, Hiroya; Connolly, Edward J; Kim, Ivana; Gragoudas, Evangelos S; Miller, Joan W; Olsen, Bjorn R

    2007-12-01

    Endostatin, a fragment of the basement membrane component collagen XVIII, exhibits antiangiogenic properties in vitro and in vivo when high doses are administered. It is not known whether endogenous endostatin at physiological levels has a protective role as an inhibitor of pathological angiogenesis, such as choroidal neovascularization (CNV) in age-related macular degeneration. Using a laser injury model, we induced CNV in mice lacking collagen XVIII/endostatin and in control mice. CNV lesions in mutant mice were approximately 3-fold larger than in control mice and showed increased vascular leakage. These differences were independent of age-related changes at the choroid-retina interface. Ultrastructural analysis of the choroidal vasculature in mutant mice excluded morphological vascular abnormalities as a cause for the larger CNV lesions. When recombinant endostatin was administered to collagen XVIII/endostatin-deficient mice, CNV lesions were similar to those seen in control mice. In control mice treated with recombinant endostatin, CNV lesions were almost undetectable. These findings demonstrate that endogenous endostatin is an inhibitor of induced angiogenesis and that administration of endostatin potently inhibits CNV growth and vascular leakage. Endostatin may have a regulatory role in the pathogenesis of CNV and could be used therapeutically to inhibit growth and leakage of CNV lesions. PMID:17526870

  15. [Polypoidal choroidal vasculopathy].

    PubMed

    Yuzawa, Mitsuko

    2012-03-01

    Polypoidal choroidal vasculopathy (PCV) is characterized by a branching vascular network with polypoidal lesions under the retinal pigment epithelium (RPE). In Japan, it is classified as a specific form of exudative age-related macular degeneration. However, several issues which we investigated regarding the pathogenesis and treatment of PCV remain unresolved. We investigated the pathogenesis, clinical findings and treatment of PCV. 1. Indocyanine green angiographic findings. There were two different patterns on indocyanine green angiograms. In the first pattern, both feeder and draining vessels were visible and network vessels showed characteristic findings of choroidal neovascularization (CNV). Points of focal dilatation on marginal vessels were comprised of polypoidal lesions. In the second pattern, neither feeder nor draining vessels were visible and there were few network vessels. The points of deformation of network vessels appeared to be polypoidal lesions. The former represents a deformation of CNV, i.e. polypoidal CNV; the latter is thought to result from abnormalities of the choroidal vessels, i.e. PCV in the strict sense. 2. Pathological findings of PCV in the strict sense. The histopathological characteristics of PCV in the strict sense, which had been eliminated by vitrectomy, were dilatation and hyalinization of vessels, massive exudative changes in blood plasma, basement membrane-like deposits and scant granulomatous tissue. These vessels were located beneath Bruch's membrane. The findings indicate that PCV in the strict sense arises from hyalinized arteriolosclerosis of choroidal vessels. 3. Optical coherence tomographic findings. A break was found in the high reflective line which revealed Bruch's membrane. Low reflective tissue was observed at the break corresponding to a feeder vessel. The high reflective line which corresponded to the retinal pigment epithelium was uneven, and highly elevated portions of the RPE corresponded to thick network

  16. Choroidal imaging: A review

    PubMed Central

    Chhablani, Jay; Wong, Ian Y.; Kozak, Igor

    2014-01-01

    Being the most vascular tissue of the eye, importance of the choroid has been very well established in various retinal and chorio-retinal diseases. Understanding of the choroidal structures has improved significantly since the evolution of enhanced depth imaging. Quantitative assessment of choroidal measurements has been found to be reproducible using different devices. This review article describes factors affecting choroidal thickness and choroidal changes in several diseases and reports its clinical importance. Evaluation of choroid would provide insight into the pathogenesis, treatment planning and follow up in chorioretinal diseases. PMID:24843305

  17. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  18. Choroidal and cutaneous metastasis from gastric adenocarcinoma.

    PubMed

    Kawai, Shoichiro; Nishida, Tsutomu; Hayashi, Yoshito; Ezaki, Hisao; Yamada, Takuya; Shinzaki, Shinichiro; Miyazaki, Masanori; Nakai, Kei; Yakushijin, Takayuki; Watabe, Kenji; Iijima, Hideki; Tsujii, Masahiko; Nishida, Kohji; Takehara, Tetsuo

    2013-03-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. PMID:23538460

  19. Functional and genetic analysis of choroid plexus development in zebrafish

    PubMed Central

    Henson, Hannah E.; Parupalli, Chaithanyarani; Ju, Bensheng; Taylor, Michael R.

    2014-01-01

    The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFP)sj2, that expresses enhanced green fluorescent protein (EGFP) in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFP)sj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease. PMID:25426018

  20. Sector iris hemangioma in association with diffuse choroidal hemangioma.

    PubMed

    Shields, Carol L; Atalay, Hatice Tuba; Wuthisiri, Wadakarn; Levin, Alex V; Lally, Sara E; Shields, Jerry A

    2015-02-01

    Two patients referred for iris lesions were found to have sector hemangioma of the iris stroma in contiguity with diffuse choroidal hemangioma. Neither patient had other manifestations of Sturge-Weber syndrome. PMID:25727597

  1. Inflammatory Choroidal Neovascularization

    PubMed Central

    Neri, Piergiorgi; Lettieri, Marta; Fortuna, Cinzia; Manoni, Mara; Giovannini, Alfonso

    2009-01-01

    Purpose and Methods: Choroidal neovascularization (CNV) can be a severe sight-threatening sequela, which can be secondary to both infectious and noninfectious uveitis. This review summarizes the different diseases associated with CNV, highlighting new treatment modalities and the possible strategies, which could be applied for the therapy of this occurrence. Results: Since CNV can often originate from posterior pole lesions and can be hard to identify, an accurate examination is mandatory in order to identify the correct diagnosis. In the majority of cases, fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) enable the determination of the clinical characteristics of the CNV. An infectious disease should be looked for to include a suitable therapy when available. The treatment strategy for CNV secondary to noninfectious uveal inflammations should be directed at controlling the inflammatory process. Systemic corticosteroids with or without immunosuppressive agents are indicated even when the CNV occurs with apparently inactive uveitis: Chronic subclinical inflammation can be the basis for the pathogenesis of CNV. Additional therapies aimed directly at the neovascular process, such as the intravitreal anti-Vascular Endothelial Growth Factor (VEGF) agents, are recommended particularly when the therapy shows an insufficient response. Conclusion: CNV secondary to uveitis is a severe sequela leading to significant visual impairment. ICGA is mandatory in order to obtain relevant information about the choroidal status. Several therapeutic options have been considered, but no guidelines are provided at the moment. Moreover, the current data are still only based on case reports or small series. For such reasons, further trials are mandatory to validate the preliminary available results. PMID:20404991

  2. Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization

    PubMed Central

    Lytvynchuk, Lyubomyr; Sergienko, Andrii; Lavrenchuk, Galina; Petrovski, Goran

    2015-01-01

    Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro. PMID:26491557

  3. Cerebral nitric oxide represses choroid plexus NFκB-dependent gateway activity for leukocyte trafficking

    PubMed Central

    Baruch, Kuti; Kertser, Alexander; Porat, Ziv; Schwartz, Michal

    2015-01-01

    Chronic neuroinflammation is evident in brain aging and neurodegenerative disorders and is often associated with excessive nitric oxide (NO) production within the central nervous system (CNS). Under such conditions, increased NO levels are observed at the choroid plexus (CP), an epithelial layer that forms the blood–cerebrospinal fluid barrier (BCSFB) and serves as a selective gateway for leukocyte entry to the CNS in homeostasis and following injury. Here, we hypothesized that elevated cerebral NO levels interfere with CP gateway activity. We found that induction of leukocyte trafficking determinants by the CP and sequential leukocyte entry to the CSF are dependent on the CP epithelial NFκB/p65 signaling pathway, which was inhibited upon exposure to NO. Examining the CP in 5XFAD transgenic mouse model of Alzheimer's disease (AD-Tg) revealed impaired ability to mount an NFκB/p65-dependent response. Systemic administration of an NO scavenger in AD-Tg mice alleviated NFκB/p65 suppression at the CP and augmented its gateway activity. Together, our findings identify cerebral NO as a negative regulator of CP gateway activity for immune cell trafficking to the CNS. PMID:25940071

  4. Review of Choroidal Osteomas

    PubMed Central

    Alameddine, Ramzi M.; Mansour, Ahmad M.; Kahtani, Eman

    2014-01-01

    Choroidal osteomas are rare benign ossifying tumors that appear as irregular slightly elevated, yellow-white, juxtapapillary, choroidal mass with well-defined geographic borders, depigmentation of the overlying pigment epithelium; and with multiple small vascular networks on the tumor surface. Visual loss results from three mechanisms: Atrophy of the retinal pigment epithelium overlying a decalcified osteoma; serous retinal detachment over the osteoma from decompensated retinal pigment epithelium, and most commonly from choroidal neovascularization. Recent evidence points to the beneficial effects of intravitreal vascular endothelial growth factor antagonists in improving visual acuity in serous retinal detachment with or without choroidal neovascularization. PMID:25100910

  5. Choroid plexus cyst in a dog.

    PubMed

    Galano, Heather R; Platt, Simon R; Neuwirth, Lisa; Quist, Charlotte F; de Lahunta, Alexander

    2002-01-01

    A 6-year-old male Doberman Pinscher had a 2-month history of dysequilibrium. Lesion localization was determined to be the cerebellomedullary pontine angle. In computed tomographic images, a well-defined, circular, hypoattenuating mass was visible at the cerebellomedullary pontine angle. The lesion, which was isoattenuating to cerebrospinal fluid, was 4 x 8 mm in diameter. Peripheral ring enhancement was evident after contrast medium administration. A choroid plexus cyst was diagnosed histopathologically. PMID:12174999

  6. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration.

    PubMed

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-01

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas "plasma" that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV. PMID:25573059

  7. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration

    PubMed Central

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-01

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas “plasma” that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV. PMID:25573059

  8. THE MULTIFUNCTIONAL CHOROID

    PubMed Central

    Nickla, Debora L.; Wallman, Josh

    2010-01-01

    The choroid of the eye is primarily a vascular structure supplying the outer retina. It has several unusual features: It contains large membrane-lined lacunae, which, at least in birds, function as part of the lymphatic drainage of the eye and which can change their volume dramatically, thereby changing the thickness of the choroid as much as four-fold over a few days (much less in primates). It contains non-vascular smooth muscle cells, especially behind the fovea, the contraction of which may thin the choroid, thereby opposing the thickening caused by expansion of the lacunae. It has intrinsic choroidal neurons, also mostly behind the central retina, which may control these muscles and may modulate choroidal blood-flow as well. These neurons receive sympathetic, parasympathetic and nitrergic innervation. The choroid has several functions: Its vasculature is the major supply for the outer retina; impairment of the flow of oxygen from choroid to retina may cause Age-Related Macular Degeneration. The choroidal blood flow, which is as great as in any other organ, may also cool and warm the retina. In addition to its vascular functions, the choroid contains secretory cells, probably involved in modulation of vascularization and in growth of the sclera. Finally, the dramatic changes in choroidal thickness move the retina forward and back, bringing the photoreceptors into the plane of focus, a function demonstrated by the thinning of the choroid that occurs when the focal plane is moved back by the wearing of negative lenses, and, conversely, by the thickening that occurs when positive lenses are worn. In addition to focusing the eye, more slowly than accommodation and more quickly than emmetropization, we argue that the choroidal thickness changes also are correlated with changes in the growth of the sclera, and hence of the eye. Because transient increases in choroidal thickness are followed by a prolonged decrease in synthesis of extracellular matrix molecules and a

  9. Metastatic Small-Cell Neuroendocrine Carcinoma Simulating Circumscribed Choroidal Hemangioma

    PubMed Central

    Leahy, Kate E.; Karaconji, Tanya; Thanni, Valli; Achan, Anita; Fung, Adrian T.

    2015-01-01

    Aim To report a case of metastatic small-cell neuroendocrine carcinoma presenting as an isolated choroidal mass and initially misdiagnosed as a circumscribed choroidal hemangioma. Methods The clinical history, fundus findings, imaging, cytology and immunohistochemical features are described. Results An otherwise healthy 66-year-old man was referred for a left nasal scotoma and a diagnosis of circumscribed choroidal hemangioma. Cytology showed cohesive clusters of small-to-intermediate malignant cells. The atypical cells stained positively for chromogranin, thyroid transcription factor-1 and synaptophysin consistent with small-cell neuroendocrine carcinoma. Conclusion Small-cell neuroendocrine carcinoma metastatic to the choroid is extremely rare; however, it is particularly aggressive and should be included in the differential diagnosis of isolated choroidal lesions, even in otherwise healthy patients. PMID:27171748

  10. Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.

    PubMed

    Wang, Haibo; Fotheringham, Lori; Wittchen, Erika S; Hartnett, M Elizabeth

    2015-12-01

    Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α-induced ROS generation. Apocynin reduced TNF-α-induced NF-κB and Rac1 activation, and inhibited TNF-α-induced CEC migration. TNF-α-induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α-induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2'-O-Me-cAMP prevented TNF-α-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α-induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process. PMID:26476350

  11. Increased macular choroidal blood flow velocity and decreased choroidal thickness with regression of punctate inner choroidopathy

    PubMed Central

    2014-01-01

    Background Changes in choroidal circulation hemodynamics during the course of punctate inner choroidopathy (PIC) remain unknown. The aim of this study was to quantitatively evaluate changes in choroidal blood flow velocity by using laser speckle flowgraphy (LSFG) in patients with PIC. Case presentation This PIC patient was initially treated with systemic corticosteroids for 4 months. LSFG measurements were taken 10 consecutive times before treatment and at 1, 3, 12, 20 and 23 months after the initiation of therapy. The mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Circles 1, 2 and 3 were set at the fovea, a lesion site, and an area of normal-appearing retina, respectively. The PIC lesions scarred after treatment along with improvements in visual function and outer retinal morphology. When the changing rate of macular flow over the 12-month follow-up period was compared with the MBR before treatment (100%), an increase of 16–37%, 24–49% and 15–18% was detected in Circles 1, 2 and 3, respectively. At the time of PIC recurrence after 20 months, the MBR decreased temporarily but subsequently increased after retreatment with systemic corticosteroids. This trend was accompanied by a decrease in choroidal thickness at the lesion site after retreatment. Conclusions Macular choroidal blood flow velocity increased and choroidal thickness decreased concurrently with regression of PIC. The present findings suggest that inflammation-related impairments in choroidal circulation may relate to the pathogenesis of PIC, extending over a wider area in the posterior pole than the PIC lesions per se. PMID:24885365

  12. Bilateral anterior choroidal artery infarction presenting with progressive somnolence.

    PubMed

    van Son, Brechtje; Vandevenne, Jan; Viaene, Pieter

    2014-09-01

    A 55-year-old woman was admitted with a 3 days history of increasing lethargy with bradyphrenia and apathy. She progressively developed severe somnolence with marked abulia, right hemiparesis, right hemianopsia, and pseudobulbar palsy. Brain magnetic resonance imaging showed the rare image of bilateral acute anterior choroidal artery infarction. Pseudobulbar mutism and in rare cases abulia have been described in acute anterior choroidal artery infarction contralateral to an older lesion in mirror position. Although neurologic deterioration is not infrequent in anterior choroidal artery territory infarcts, the absence of focal neurologic signs on admission is rare and did not raise suspicion of acute stroke. PMID:25106836

  13. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  14. Nucleus accumbens core lesions enhance two-way active avoidance.

    PubMed

    Lichtenberg, N T; Kashtelyan, V; Burton, A C; Bissonette, G B; Roesch, M R

    2014-01-31

    The majority of work examining the nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to the NAc as being critical for motivating behavior toward desirable outcomes. For example, we have recently shown that lesions of the NAc impaired performance on a reward-guided decision-making task that required rats to choose between differently valued rewards. Unfortunately, much less is known about the role that the NAc plays in motivating behavior when aversive outcomes are predicted. To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance. PMID:24275320

  15. Laser-induced macular holes demonstrate impaired choroidal perfusion

    NASA Astrophysics Data System (ADS)

    Brown, Jeremiah, Jr.; Allen, Ronald D.; Zwick, Harry; Schuschereba, Steven T.; Lund, David J.; Stuck, Bruce E.

    2003-06-01

    Choroidal perfusion was evaluated following the creation of a laser induced macular hole in a nonhuman primate model. Two Rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green (ICG) angiography . Each lesion produced vitreous hemorrhage and progressed to a full thickness macular hole. ICG angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. Nd:YAG, laser-induced macular holes result in long term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris.

  16. Psammoma bodies - friends or foes of the aging choroid plexus.

    PubMed

    Jovanović, Ivan; Ugrenović, Sladjana; Vasović, Ljiljana; Petrović, Dragan; Cekić, Sonja

    2010-06-01

    Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma

  17. Unilateral optic nerve head and choroidal metastases from a bronchial carcinoma.

    PubMed

    Hayreh, S S; Blodi, F C; Silbermann, N N; Summers, T B; Potter, P H

    1982-01-01

    A 61-year-old man presented with uniocular gradually progressive visual loss, pain in the eye, visual activity of 6/60, markedly constricted visual fields, optic disc edema, retinal pigment epithelial disturbance at the posterior pole, and markedly delayed filling of the choroid on angiography, with a normal fellow eye. He had suffered from recurrent seizures for 15 years, with some evidence of cortical demyelination. Erythrocyte sedimentation rate was elevated. About 5 months after the onset of visual disturbance, evidence of bronchial carcinoma became apparent and he died 6 weeks later. The etiology of his ocular lesions was established only by histopathological evidence of metastases into the optic nerve head and the choroid. Diagnostic problems presented by the ocular findings are discussed. PMID:7145334

  18. Bilateral Presumed Tuberculous Choroiditis

    PubMed Central

    Mohammadi, Naseh; Ghassemi, Fariba; Shojaei, Esfandiar; Moradnejad, Pardis

    2016-01-01

    Purpose: To describe a case of bilateral presumed tuberculous choroiditis which resolved promptly with a short course of antituberculous therapy. Case Report: A 44-year-old lady presented with bilateral visual loss of 8 months’duration. Considering the presence of pan-uveitis, severe macular edema, multifocal leakage on fluorescein angiography, positive tuberculin skin test, and after excluding other diseases, she underwent anti-tuberculous therapy (ATT) for disseminated choroiditis due to presumed ocular tuberculosis. She improved promptly and completely. There were no signs of relapse 18 months after completion of the treatment course. In a young patient with disseminated choroiditis and relatively short duration of symptoms, a course of ATT for 6 months may effectively treat the disease preventing relapse for a considerable period of time. Conclusion: In Presumed Tuberculous chroiditis early diagnosis is crucial for prompt and complete improvement. PMID:27413507

  19. The choroid plexuses and their impact on developmental neurogenesis

    PubMed Central

    Johansson, Pia A.

    2014-01-01

    During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development. PMID:25386116

  20. IL-17/Th17 Pathway Is Activated in Acne Lesions

    PubMed Central

    Kelhälä, Hanna-Leena; Palatsi, Riitta; Fyhrquist, Nanna; Lehtimäki, Sari; Väyrynen, Juha P.; Kallioinen, Matti; Kubin, Minna E.; Greco, Dario; Tasanen, Kaisa; Alenius, Harri; Bertino, Beatrice; Carlavan, Isabelle; Mehul, Bruno; Déret, Sophie; Reiniche, Pascale; Martel, Philippe; Marty, Carine; Blume-Peytavi, Ulrike; Voegel, Johannes J.; Lauerma, Antti

    2014-01-01

    The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy. PMID:25153527

  1. Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions

    PubMed Central

    Metz, Imke; Weigand, Stephen D; Popescu, Bogdan F G; Frischer, Josa M; Parisi, Joseph E; Guo, Yong; Lassmann, Hans; Brück, Wolfgang; Lucchinetti, Claudia F.

    2014-01-01

    Objective Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods Archival tissue samples derived from patients with pathologically confirmed CNS inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy, were analyzed immunohistochemically. Inclusion criteria was the presence of early active demyelinating lesions - required for immunopattern classification - obtained from the same patient at two or more time points. Results Among 1321 surgical biopsies consistent with MS, 22 cases met study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches. PMID:24771535

  2. Improved assessment of laser-induced choroidal neovascularization

    PubMed Central

    Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.; Kim, Stephen J.

    2011-01-01

    The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology. PMID:20553963

  3. Is Asthma Related to Choroidal Neovascularization?

    PubMed Central

    Hou, Jing; Gong, Peihua; Zheng, Yi; Zhao, Mingwei; Zhou, Peng; Li, Xiaoxin

    2012-01-01

    Background Age-related degeneration(AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. Principal Findings The epidemiological study showed that asthma was related to choroidal neovascularization(CNV) subtype(OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α’-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. Significance This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice. PMID:22567103

  4. Metatranscriptomics reveals overall active bacterial composition in caries lesions

    PubMed Central

    Simón-Soro, Aurea; Guillen-Navarro, Miriam; Mira, Alex

    2014-01-01

    Background Identifying the microbial species in caries lesions is instrumental to determine the etiology of dental caries. However, a significant proportion of bacteria in carious lesions have not been cultured, and the use of molecular methods has been limited to DNA-based approaches, which detect both active and inactive or dead microorganisms. Objective To identify the RNA-based, metabolically active bacterial composition of caries lesions at different stages of disease progression in order to provide a list of potential etiological agents of tooth decay. Design Non-cavitated enamel caries lesions (n=15) and dentin caries lesions samples (n=12) were collected from 13 individuals. RNA was extracted and cDNA was constructed, which was used to amplify the 16S rRNA gene. The resulting 780 bp polymerase chain reaction products were pyrosequenced using Titanium-plus chemistry, and the sequences obtained were used to determine the bacterial composition. Results A mean of 4,900 sequences of the 16S rRNA gene with an average read length of 661 bp was obtained per sample, giving a comprehensive view of the active bacterial communities in caries lesions. Estimates of bacterial diversity indicate that the microbiota of cavities is highly complex, each sample containing between 70 and 400 metabolically active species. The composition of these bacterial consortia varied among individuals and between caries lesions of the same individuals. In addition, enamel and dentin lesions had a different bacterial makeup. Lactobacilli were found almost exclusively in dentin cavities. Streptococci accounted for 40% of the total active community in enamel caries, and 20% in dentin caries. However, Streptococcus mutans represented only 0.02–0.73% of the total bacterial community. Conclusions The data indicate that the etiology of dental caries is tissue dependent and that the disease has a clear polymicrobial origin. The low proportion of mutans streptococci detected confirms that they

  5. CHOROIDAL MORPHOLOGY IN A PATIENT WITH HELLP SYNDROME

    PubMed Central

    Kasai, Ayaka; Sugano, Yukinori; Maruko, Ichiro

    2016-01-01

    Purpose: We report here, the morphological characteristics of the retina and choroid in a patient with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, who was not aware of her pregnancy before visiting our hospital. Methods: Case report. Results: The patient complained of visual disturbances in both eyes for a few days. Extensive serous retinal detachment and hyperreflective foci were observed in both eyes on spectral domain optical coherence tomography (SDOCT). Enhanced depth imaging technique using SDOCT revealed choroidal thickening and unclear choroidal vessel contour. Her blood pressure was 230/168 mmHg. Laboratory data showed hemolysis and liver dysfunction. Obstetrical examination disclosed her pregnancy. She was diagnosed as having HELLP syndrome. Because her general condition improved after prompt Cesarean delivery, the fundus lesions were rapidly resolved with choroidal thinning. Conclusion: The eyes in a patient with HELLP syndrome showed characteristic choroidal morphology. The choroidal morphology shown with SDOCT might be one of the pathognomonic signs for a diagnosis of HELLP syndrome. PMID:26595148

  6. Fetal choroid plexus vascularization assessed by color flow ultrasonography.

    PubMed

    Kurjak, A; Schulman, H; Predanic, A; Predanic, M; Kupesic, S; Zalud, I

    1994-11-01

    We investigated the development of intracranial vascularization in the human fetus, with particular emphasis on the choroid plexus. The fetal brain was visualized in 102 patients with healthy pregnancies between 9 and 16 weeks' gestation. Imaging was done transvaginally except in the pregnancies of longer duration with unfavorable fetal positions. Color flow imaging was used to identify vessels in the cranium and within the choroid plexus. Pulsed Doppler signals were obtained from an internal carotid-middle cerebral artery and from a choroid plexus vessel. The pulsatility index was calculated from the Doppler spectral envelope. A major cerebral vessel could be seen at 9 weeks' gestation. Choroid plexus vessels were first seen at 10 weeks 3 days. Visualization rates ranged from 35 to 75% for plexus vessels, and 65 to 100% for cerebral vessels. Visualization of choroid plexus vessels was maximal at 13 weeks. The pulsatility index for the cerebral arteries at this gestational period averaged 2.6 +/- 0.6. The result for the choroid plexus was 1.66 +/- 0.5. (P < 0.001). Visualization of the vessels of the choroid plexus increases and decreases as the gland develops and shrinks. This developmental period also is the time of active neurogenesis. PMID:7837329

  7. Optical Coherence Tomography of Retinal and Choroidal Tumors

    PubMed Central

    Say, Emil Anthony T.; Shah, Sanket U.; Ferenczy, Sandor; Shields, Carol L.

    2011-01-01

    Optical coherence tomography (OCT) has revolutionized the field of ophthalmology since its introduction 20 years ago. Originally intended primarily for retina specialists to image the macula, it has found its role in other subspecialties that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT provides axial resolution to approximately 7 microns with cross-sectional images of the retina, delivering valuable information on the effects of intraocular tumors on the retinal architecture. Some effects include retinal edema, subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning, and retinal pigment epithelial detachment. With more advanced technology, OCT now provides imaging deeper into the choroid using a technique called enhanced depth imaging. This allows characterization of the thickness and reflective quality of small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma. Future improvements in image resolution and depth will allow better understanding of the mechanisms of visual loss, tumor growth, and tumor management. PMID:21811667

  8. Optical Coherence Tomography of Retinal and Choroidal Tumors

    PubMed Central

    Say, Emil Anthony T.; Shah, Sanket U.; Ferenczy, Sandor; Shields, Carol L.

    2012-01-01

    Optical coherence tomography (OCT) has revolutionized the field of ophthalmology since its introduction 20 years ago. Originally intended primarily for retina specialists to image the macula, it has found its role in other subspecialties that include glaucoma, cornea, and ocular oncology. In ocular oncology, OCT provides axial resolution to approximately 7 microns with cross-sectional images of the retina, delivering valuable information on the effects of intraocular tumors on the retinal architecture. Some effects include retinal edema, subretinal fluid, retinal atrophy, photoreceptor loss, outer retinal thinning, and retinal pigment epithelial detachment. With more advanced technology, OCT now provides imaging deeper into the choroid using a technique called enhanced depth imaging. This allows characterization of the thickness and reflective quality of small (<3 mm thick) choroidal lesions including choroidal nevus and melanoma. Future improvements in image resolution and depth will allow better understanding of the mechanisms of visual loss, tumor growth, and tumor management. PMID:23008756

  9. Massive choroidal hemorrhage associated with low molecular weight heparin therapy.

    PubMed

    Neudorfer, M; Leibovitch, I; Goldstein, M; Loewenstein, A

    2002-04-01

    An 84-year-old woman with unstable angina pectoris was treated with subcutaneous enoxaparine (Clexane) for several days before presenting with severe pain and decreased vision in her left eye. The intraocular pressure was 70 mmHg, and fundus examination showed a pigmented choroidal lesion and associated choroidal and retinal detachment. Ultrasonography was consistent with choroidal hemorrhage, and she was diagnosed as having acute glaucoma secondary to massive subchoroidal hemorrhage. Medical control of the intraocular pressure resulted in a significant clinical improvement. Intraocular hemorrhage and angle-closure glaucoma are rare and previously unreported complications in patients treated with low molecular weight heparin. It is important to be aware of this ocular complication as these drugs are so often used. PMID:11943940

  10. Peripapillary choroidal thickness in childhood.

    PubMed

    Read, Scott A; Alonso-Caneiro, David; Vincent, Stephen J; Collins, Michael J

    2015-06-01

    Changes in the thickness of the invivo peripapillary choroid have been documented in a range of ocular conditions in adults; however, choroidal thickness in the peripapillary region of children has not been examined in detail. This study therefore aimed to investigate the thickness of the peripapillary choroid and the overlying retinal nerve fibre layer (RNFL) in a population of normal children with a range of refractive errors. Ninety-three children (37 myopes and 56 non-myopes) aged between 11 and 16 years, had measurements of peripapillary choroidal and RNFL thickness derived from enhanced depth imaging optical coherence tomography images (EDI-OCT, Heidelberg Spectralis). The average thickness was determined in a series of five 0.25 mm width concentric annuli (each divided into 8 equal sized 45° sectors) centred on the optic nerve head boundary, accounting for individual ocular magnification factors and the disc-fovea angle. Significant variations in peripapillary choroidal thickness were found to occur with both annulus location (p < 0.001) and sector position (p < 0.001) in this population of children. The innermost annulus (closest to the edge of the optic disc) exhibited the thinnest choroid (mean 77 ± 16 μm) and the outermost annulus, the thickest choroid (191 ± 52 μm). The choroid was thinnest inferior to the optic nerve head (139 ± 38 μm) and was thickest in the superior temporal sector (157 ± 40 μm). Significant differences in the distribution of choroidal thickness were also associated with myopia, with myopic children having significantly thinner choroids in the inner and outer annuli of the nasal and temporal sectors respectively (p < 0.001). RNFL thickness also varied significantly with annulus location and sector (p < 0.001), and showed differences in thickness distribution associated with refractive error. This study establishes the normal variations in the thickness of the peripapillary choroid with radial distance and azimuthal angle

  11. Examining the Choroid in Ocular Inflammation: A Focus on Enhanced Depth Imaging

    PubMed Central

    Baltmr, Abeir; Lightman, Sue; Tomkins-Netzer, Oren

    2014-01-01

    The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT) is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation. PMID:25024846

  12. A Case of Choroidal Melanoma Metastatic to the Breast

    PubMed Central

    Taran-Munteanu, L.; Hartkopf, A.; Eigentler, T. K.; Vogel, U.; Brucker, S.; Taran, F. A.

    2016-01-01

    A 61-year-old woman developed blurred vision in her left eye in December 2006. A clinical diagnosis of choroidal melanoma was made. The patient underwent excision of the left lens, followed by vitrectomy and stereotactic radiotherapy. She remained systemically healthy until 50 months later when, during a CT scan done for staging purposes, a newly visible lump was noted in the lower quadrant of her left breast. Core needle biopsy of the lesion in the left breast was performed, and histologic examination revealed metastasis from the choroidal melanoma. The patient underwent breast-conserving surgery of the left breast. Definitive histological examination showed clear tumor margins in the resected specimen and one sentinel lymph node without evidence of metastatic cells. Twenty-nine months after surgery, a similar nodule was detected in the upper quadrant of the left breast. Core biopsy again showed metastatic melanoma, and similar breast-conserving surgery was performed. Systemic examination, including magnetic resonance imaging of the head and computed tomography of the pelvis, abdomen, and chest, was done regularly and revealed no significant findings. Solitary breast metastases from choroidal melanoma are extremely rare. Nevertheless, clinicians should be aware of this rare form of metastasis when treating patients with suspicious breast lesions and a history of choroidal melanoma. If solitary metastasis is confirmed, then breast-conserving surgery may be recommended. PMID:27239068

  13. Choroid plexus cysts and aneuploidy.

    PubMed Central

    Peleg, D; Yankowitz, J

    1998-01-01

    The association of choroid plexus cysts with fetal aneuploidy, particularly trisomy 18, was first noted in 1986. Through the years there have been numerous reports on this subject, but no consensus has been reached with regard to chromosomal risk. In this review, we attempt to summarise published reports on second trimester choroid plexus cysts, with an emphasis on the strengths and weaknesses of each report. Based on these reports, additional malformations are a significant risk factor for aneuploidy and an indication for determination of fetal karyotype. The management of isolated choroid plexus cysts remains controversial. PMID:9678699

  14. Growing Hemorrhagic Choroidal Fissure Cyst

    PubMed Central

    Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit

    2016-01-01

    Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426

  15. Intravitreal bevacizumab monotherapy for choroidal neovascularisation secondary to choroidal osteoma.

    PubMed

    Papastefanou, V P; Pefkianaki, M; Al Harby, L; Arora, A K; Cohen, V M L; Andrews, R M; Sagoo, M S

    2016-06-01

    PurposeThe purpose of this study is to present the outcomes of a series of patients with choroidal neovascular membrane (choroidal neovascularisation (CNV)) secondary to a choroidal osteoma undergoing anti-VEGF monotherapy.Patients and methodsRetrospective series of patients with choroidal neovascularization secondary to choroidal osteoma. All patients underwent clinical and imaging assessment (fundus photo, B-scan ultrasonography, fluorescein angiography, and optical coherence tomography-where available), and were managed with intravitreal anti-VEGF injections (Bevacizumab). Visual acuity and central retinal thickness were recorded pre treatment and at the end of the follow-up period.ResultsEight patients were included in this study. Of this, 6/8 had predominantly classic or classic and 2/8 patients had minimally classic or occult CNV. Each patient received 3-10 injections of bevacizumab. Median follow-up was 9 months (3-15 months). Visual acuity improved in 5 patients, by 2-6 Snellen lines. CNV completely regressed in 5 cases and partially regressed in 3 cases. Mean CRT reduction was 122 μm (6 to -230 μm).ConclusionIntravitreal bevacizumab can be an effective treatment modality in the management of vision threatening CNV secondary to choroidal osteoma. PMID:27034203

  16. Emerging Treatments for Choroidal Metastases

    PubMed Central

    Chen, Connie J.; McCoy, Allison N.; Brahmer, Julie; Handa, James T.

    2015-01-01

    It has been over a century since Perls described the first case of choroidal metastasis. For the next six decades only 230 cases were described in the literature. Today, however, ocular metastasis is recognized as the most common intraocular malignancy. Thanks to recent advances in treatment options for metastatic disease, patients are living longer, and choroidal metastases will become an increasingly important issue for oncologists and ophthalmologists alike. We summarize the current knowledge of choroidal metastases and examine their emerging systemic and local therapies. Targeted therapies for metastatic lung, breast, and colon cancer—the most common causes of choroidal metastases—are reviewed in detail with the goal of identifying the most effective treatment strategies. PMID:22117885

  17. Xanthogranuloma of the choroid plexus

    SciTech Connect

    Pear, B.L.

    1984-08-01

    Uncommon tumefactions known as xanthogranulomas can occur throughout the body. Some appear to develop as benign or malignant neoplasms. An even less familiar xanthogranuloma occurs within the choroid plexus. Most are tiny plaques only a few millimeters in diameter. However, they can present as masses of significant size within the glomus. When large and unilateral, they are included in the differential diagnosis of choroid plexus tumors. A computed tomographic (CT) study of such a tumor is presented.

  18. EN FACE IMAGING OF THE CHOROID IN POLYPOIDAL CHOROIDAL VASCULOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    Alasil, Tarek; Ferrara, Daniela; Adhi, Mehreen; Brewer, Erika; Kraus, Martin F; Baumal, Caroline R; Hornegger, Joachim; Fujimoto, James G; Witkin, Andre J; Reichel, Elias; Duker, Jay S; Waheed, Nadia K

    2014-01-01

    Objective To define morphological features of polypoidal choroidal vasculopathy (PCV) using en face images from swept source optical coherence tomography (SS-OCT). Design Prospective cross-sectional study. Methods Ten eyes from 6 patients with PCV and 10 eyes from 5 age-matched normal subjects. All subjects were prospectively scanned with a prototype SS-OCT system. A motion correction algorithm was applied to correct and merge scans into a single volumetric dataset. En face images were generated at intervals of 4.13 μm (1 pixel) relative to the Bruch’s membrane. Results Age ± standard deviation for the normal group was 62.4 (±12.1) years and for the PCV group was 68.3 (±5.2) years. En face SS-OCT imaging of PCV eyes demonstrated the relationship between larger pigment epithelial detachments (PEDs) and small adjoining PEDs which correlated with the polypoidal lesions seen on indocyanine green angiography in all PCV eyes. En face SS-OCT demonstrated choroidal vascular abnormalities in 7 out of 7 eyes with PCV, and in 2 out of 3 enrolled fellow eyes in patients with unilateral PCV. Out of 7 PCV eyes, focal choroidal vascular dilatation was noted in 3 eyes and diffuse choroidal vascular dilatation was noted in 1 eye. In addition, a branching vascular network was noted above Bruch’s membrane in 1 eye, below Bruch’s membrane within the choriocapillaris in 1 eye, and in the larger choroidal vascular layer in 1 eye. Conclusions En face SS-OCT provides an in vivo tool to visualize the pathological features and the choroidal vasculature in PCV. PMID:25528955

  19. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Zhang, Yan; Wildsoet, Christine F.

    2016-01-01

    Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia. PMID:26310157

  20. Topographic congruence of calcified parenchymal neurocysticercosis and other structural brain lesions with epileptiform activity

    PubMed Central

    Saito, Erin K; Nagpal, Meera; Leon, Amanda; Mehta, Bijal; McMurtray, Aaron Matthew

    2016-01-01

    Introduction: Calcified parenchymal neurocysticercosis (NCC) lesions are commonly detected in many individuals with refractory epilepsy. However, the relationship between these lesions and epilepsy is not fully determined. We sought to determine if calcified parenchymal NCC demonstrated topographic congruence with epileptiform activity in refractory epilepsy patients. Additional patients with other structural brain lesions were included for comparison. Subjects and Methods: Retrospective cross-sectional analysis of all patients treated at a community-based neurology clinic for refractory epilepsy during a 3-month period and with structural brain lesions detected by neuroimaging studies. Results: A total of 105 patients were included in the study, including 63 with calcified parenchymal NCC lesions and 42 with other structural brain lesions. No significant relationship was detected between hemispheric localization of calcified parenchymal NCC lesions and epileptiform activity. For those with other structural brain lesions, the hemispheric localization was significantly related to the side of epileptiform activity (Chi-square = 11.13, P = 0.025). In addition, logistic regression models showed that those with right-sided non-NCC lesions were more likely to have right-sided epileptiform activity (odds ratio = 4.36, 95% confidence interval [CI] =1.16–16.31, P = 0.029), and those with left-sided non-NCC lesions were more likely to have left-sided epileptiform activity (odds ratio = 7.60, 95% CI = 1.89–30.49, P = 0.004). Conclusion: The lack of correlation between the side of calcified parenchymal NCC lesions and the side of the epileptiform activity suggests that these lesions may be incidental findings in many patients. PMID:26998434

  1. A rare case of congenital choroid plexus carcinoma.

    PubMed

    Wilhelm, Miriam; Hirsch, Wolfgang; Merkenschlager, Andreas; Stepan, Holger; Geyer, Christian; Kiess, Wieland

    2012-10-01

    We report a 1-year-old child with the prenatal (week 29 + 5) diagnosis of a brain tumor. The parents were informed about all aspects of prognosis and options concerning termination of pregnancy. The parents opted for an aggressive therapeutic approach after extensive and informative case conferences and counseling. The histopathological diagnosis after partial tumor resection was choroid plexus carcinoma, two weeks thereafter tumor size was progressive. The parents opted for palliative treatment at this stage. The patient died at the age of one year. Ethical aspects have to be actively considered and addressed when caring for children with choroid plexus carcinoma. PMID:22881717

  2. Unsuspected Ganglioneuroma of the Choroid Diagnosed after Enucleation

    PubMed Central

    Mbagwu, Michael; Rahmani, Bahram; Srivastava, Arth; Burrowes, Delilah; Bryar, Paul J.

    2015-01-01

    We report a case of an unsuspected ganglioneuroma of the choroid in a patient with neurofibromatosis type 1. A 5-year-old girl presented from an outside institution with right proptosis and glaucoma since birth. Magnetic resonance imaging was obtained and showed a cavernous sinus mass extending into the right orbit and multiple orbital lesions. Additionally, increased signal in the posterior globe of the right eye was noted, but its etiology was unclear at the time. She was lost to follow-up for 3 years and later returned with a blind painful eye. Enucleation was performed, and histopathology was significant for diffuse choroidal ganglioneuroma and advanced glaucoma. We report the atypical history, examination findings, and histopathology to support the diagnosis. PMID:27171204

  3. Hemodynamics of focal choroidal excavations.

    PubMed

    Soma, Ryoko; Moriyama, Muka; Ohno-Matsui, Kyoko

    2015-04-01

    The purpose of this study was to investigate the hemodynamics of focal choroidal excavations (FCEs). Four eyes of four patients with a FCE were studied. Indocyanine green angiography (ICGA), laser speckle flowgraphy (LSFG), optical coherence tomography (OCT), and multi-focal electroretinography (mfERG) were performed to investigate the choroidal hemodynamics and the morphological and functional changes. The mean depth of the FCE determined by OCT was 222.5 ± 49.5 μm with a range of 164-272 μm. In one case, subretinal fluid was observed in the excavation, and in three cases, subretinal fluid was not observed. ICGA showed hypofluorescence, and laser flowgraphy (LSFG) showed decreased choroidal blood flow at the excavation in all cases. Three cases were symptomatic, and the amplitudes of the mfERGs were reduced. FCEs cause a decrease of choroidal blood flow. In three of four cases, the mfERGs were depressed over the FCEs leading to symptoms. PMID:25626897

  4. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  5. Clinical applications of choroidal imaging technologies.

    PubMed

    Chhablani, Jay; Barteselli, Giulio

    2015-05-01

    Choroid supplies the major blood supply to the eye, especially the outer retinal structures. Its understanding has significantly improved with the advent of advanced imaging modalities such as enhanced depth imaging technique and the newer swept source optical coherence tomography. Recent literature reports the findings of choroidal changes, quantitative as well as qualitative, in various chorioretinal disorders. This review article describes applications of choroidal imaging in the management of common diseases such as age-related macular degeneration, high myopia, central serous chorioretinopathy, chorioretinal inflammatory diseases, and tumors. This article briefly discusses future directions in choroidal imaging including angiography. PMID:26139797

  6. Fish biomarkers for environmental monitoring: An integrated model supporting enzyme activity and histopathological lesions

    NASA Astrophysics Data System (ADS)

    Neta, Raimunda Nonata Fortes Carvalho; Torres Junior, Audalio Rebelo

    2014-10-01

    We present a mathematical model describing the association between glutathione-S-transferase activity and brachial lesions in the catfish, Sciades herzbergii (Ariidae) from a polluted port. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Brazil. Two biomarkers, hepatic glutathione S-transferase (GST) activity and histopathological lesions, in gills tissue were measured. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. The model developed in this study indicates that branchial and hepatic lesions are initiated when GST activity reaches 2.15 μmol min-1 mg protein-1. Beyond this limit, GST activity decreased to very low levels and irreversible histopathological lesions occurred. This mathematical model provides a realistic approach to analyze predictive biomarkers of environmental health status.

  7. Loss of circadian rhythmicity in body temperature and locomotor activity following suprachiasmatic lesions in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Haro, P. J.; Winget, C. M.

    1977-01-01

    In experiments on male and female ambulatory rats, the effect of bilateral suprachiasmatic lesions on deep body temperature and locomotor activity circadian rhythms was investigated. A L/D:12/12 cycle and 23 C ambient temperature were maintained. One-half of the rats received radiofrequency lesions in the suprachiasmic nucleus (SCN) while the second group were sham operated by lowering the radiofrequency electrode to the SCN without producing electrolytic lesions. Four weeks were allowed for recuperation. Autopsies were conducted to make sure that the lesions were restricted to SCN. The results show the complete disappearance of circadian rhythm in the SCN lesioned rats and only a slight diminution for the sham operated rats.

  8. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M. Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  9. Neuroprotectin D1 Attenuates Laser-induced Choroidal Neovascularization in Mouse

    PubMed Central

    Sheets, Kristopher G.; Zhou, Yongdong; Ertel, Monica K.; Knott, Eric J.; Regan, Cornelius E.; Elison, Jasmine R.; Gordon, William C.; Gjorstrup, Per

    2010-01-01

    Purpose To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. Methods C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. Results At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. Conclusions NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-κB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be

  10. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  11. Grossly calcified choroid plexus concealing foramen of Monro meningiomas as an unusual cause of obstructive hydrocephalus

    PubMed Central

    Kawaguchi, Tomohiro; Fujimura, Miki; Tominaga, Teiji

    2016-01-01

    Various intraventricular tumors can present with calcifications; however, the choroid plexus can also have physiological calcifications. This is the first case report of meningiomas located at the bilateral foramen of Monro (FOM), concealed by a grossly calcified choroid plexus, presenting with obstructive hydrocephalus. A 60-year-old woman with disturbed consciousness was admitted by ambulance. Head computed tomography revealed significantly high-density lesions that smoothly extended from the choroid plexus of the lateral ventricles to the third ventricle. They occupied both sides of the FOM, resulting in obstructive hydrocephalus. The diagnostic endoscopic biopsy was performed using a flexible neuroendoscopic system, and an egg shell-like grossly calcified choroid plexus was found to smoothly extend toward the FOM. Resection was not selected because the calcified lesions had tightly adhered to the veins and fornix; therefore, the patient underwent ventriculo-peritoneal shunting. The lesions were histologically identified as psammomatous meningiomas with low proliferation potential (the Ki-67 labeling index was lower than 1%). She was discharged 10 days after surgery without neurological deficits. As calcifications can have tumoral and nontumoral origins, we considered neuroendoscopic exploration to be essential in order to achieve an accurate diagnosis and select optimal management. PMID:26889294

  12. Grossly calcified choroid plexus concealing foramen of Monro meningiomas as an unusual cause of obstructive hydrocephalus.

    PubMed

    Kawaguchi, Tomohiro; Fujimura, Miki; Tominaga, Teiji

    2016-01-01

    Various intraventricular tumors can present with calcifications; however, the choroid plexus can also have physiological calcifications. This is the first case report of meningiomas located at the bilateral foramen of Monro (FOM), concealed by a grossly calcified choroid plexus, presenting with obstructive hydrocephalus. A 60-year-old woman with disturbed consciousness was admitted by ambulance. Head computed tomography revealed significantly high-density lesions that smoothly extended from the choroid plexus of the lateral ventricles to the third ventricle. They occupied both sides of the FOM, resulting in obstructive hydrocephalus. The diagnostic endoscopic biopsy was performed using a flexible neuroendoscopic system, and an egg shell-like grossly calcified choroid plexus was found to smoothly extend toward the FOM. Resection was not selected because the calcified lesions had tightly adhered to the veins and fornix; therefore, the patient underwent ventriculo-peritoneal shunting. The lesions were histologically identified as psammomatous meningiomas with low proliferation potential (the Ki-67 labeling index was lower than 1%). She was discharged 10 days after surgery without neurological deficits. As calcifications can have tumoral and nontumoral origins, we considered neuroendoscopic exploration to be essential in order to achieve an accurate diagnosis and select optimal management. PMID:26889294

  13. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.

    PubMed

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-07-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  14. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

    PubMed Central

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-01-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  15. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  16. Hypoxia in Leishmania major skin lesions impairs the NO-dependent leishmanicidal activity of macrophages.

    PubMed

    Mahnke, Alexander; Meier, Robert J; Schatz, Valentin; Hofmann, Julian; Castiglione, Kirstin; Schleicher, Ulrike; Wolfbeis, Otto S; Bogdan, Christian; Jantsch, Jonathan

    2014-09-01

    Cure of infections with Leishmania major is critically dependent on the ability of macrophages to induce the type 2 nitic oxide (NO) synthase (NOS2) that produces high levels of NO in the presence of ample oxygen. Therefore, we analyzed the oxygen levels found in leishmanial skin lesions and their effect on the NOS2-dependent leishmanicidal activity of macrophages (MΦ). When L. major skin lesions of self-healing C57BL/6 mice reached their maximum size, the infected tissue displayed low oxygen levels (pO2∼21 Torr). MΦ activated under these oxygen tensions failed to produce sufficient amounts of NO to clear L. major. Nos2-deficient and hypoxic wild-type macrophages displayed a similar phenotype. Killing was restored when MΦ were reoxygenated or exposed to a NO donor. The resolution of the lesion in C57BL/6 mice was paralleled by an increase of lesional pO2. When mice were kept under normobaric hypoxia, this caused a persistent suppression of the lesional pO2 and a concurrent increase of the parasite load. In Nos2-deficient mice, there was no effect of atmospheric hypoxia. Low oxygen levels found at leishmanial skin lesions impaired the NOS2-dependent leishmanicidal activity of MΦ. Hence, tissue oxygenation represents an underestimated local milieu factor that participates in the persistence of Leishmania. PMID:24583949

  17. Enhanced Ccl2-Ccr2 signaling drives more severe choroidal neovascularization with aging.

    PubMed

    Robbie, Scott J; Georgiadis, Anastasios; Barker, Susie E; Duran, Yanai; Smith, Alexander J; Ali, Robin R; Luhmann, Ulrich F O; Bainbridge, James W

    2016-04-01

    The impact of many inflammatory diseases is influenced by age-related changes in the activation of resident and circulating myeloid cells. In the eye, a major sight-threatening consequence of age-related macular degeneration is the development of severe choroidal neovascularization (CNV). To identify the molecular pathways and myeloid cell populations involved in this increased neovascular response, we characterized the immune status of murine choroid and retina during aging and in the context of experimental CNV. In the choroid, but not in the retina, advancing age is associated with proinflammatory upregulation of CCL2-CCR2 signaling. Genetic excision of CCL2 diminishes age-related inflammatory changes in the choroid, with reduced recruitment of proinflammatory myeloid cells and attenuation of CNV. These findings indicate that CCL2-driven recruitment of myeloid cells contributes to increased severity of CNV with age. Similar mechanisms may be involved in other age-related inflammatory diseases. PMID:26973110

  18. Dentin caries activity in early occlusal lesions selected to receive operative treatment

    PubMed Central

    Lehmann, Maryann; Veitz-Keenan, Analia; Matthews, Abigail G.; Vena, Donald; Grill, Ashley; Craig, Ronald G.; Curro, Frederick A.; Thompson, Van P.

    2014-01-01

    Background Members of the practice-based research network Practitioners Engaged in Applied Research and Learning (PEARL) Network investigated the dentin caries activity in early occlusal lesions and its relationship to patient age, preoperative tooth sensitivity and radio-graphic appearance, as well as its influence on preparation depth and volume. Methods PEARL Network practitioner-investigators (P-Is) (n = 45), general dentists who were trained but whose methods were not calibrated, conducted a study regarding postoperative hypersensitivity in resin-based composite restorations. The P-Is enrolled as study participants 613 patients with occlusal carious lesions that, in the P-Is’ clinical judgment, required restoration. The P-Is used baseline radiographs to assess the depth and extent of the lesions. Data for 671 restorations included baseline sensitivity; ranking of dentin caries activity on the opening of the enamel; radiographic visibility (n = 652); and measurements of preparation depth, width and length. Results P-Is found rapidly progressing dentin caries in 38.5 percent (258 of 671) of lesions and slowly progressing (and potentially inactive dentin) caries in the remainder of the lesions. Rapidly progressing caries was not related to the participant’s age or participant-reported preoperative hypersensitivity but was related to the lesion depth as seen radiographically (P < .001) and depth (P < .001) and volume (P < .001) of the preparation. Molars had slightly higher but not statistically significant levels of caries activity. Conclusion Rapidly progressing dentin caries, while present in only 38.5 percent of lesions, was related to the lesion’s radiographic appearance but not to the participant’s age or the study tooth’s pre-operative sensitivity. Clinical Implications On the basis of the low level of rapidly progressing dentin caries in this study population and the fact that slowly progressing caries can be inactive or remineralizing, the

  19. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS.

    PubMed

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05-2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65-3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07-2.23). Lesion activity was significantly associated with mother's schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15-4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother's schooling. PMID:26900846

  20. Nuclear Receptor Activity and Liver Cancer Lesion Progression

    EPA Science Inventory

    Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. We explored this question using human CAR, PXR, PPARα,...

  1. Detection and activity assessment of primary coronal caries lesions: a methodologic study.

    PubMed

    Ekstrand, Kim Rud; Martignon, Stefania; Ricketts, David James Nigel; Qvist, Vibeke

    2007-01-01

    This study has three main objectives: Study (1) test the reproducibility and accuracy of the ICDAS I and ICDAS II caries detection systems; Study (2) validate a new impression material (Clinpro, 3M ESPE), which is said to detect lactic acid in plaque fermenting sucrose; Study (3) devise and test a scoring system for the assessment of caries activity of coronal lesions. Study (1): 141 extracted teeth were examined by two examiners using the ICDAS I and ICDAS II caries detection systems and validated against a histological classification system. Study (2): The accuracy of the impression material in predicting plaque with pH lower/higher than 5.5 was determined in an in situ study of 45 root dentin specimens by comparing the color change in the impression with the actual pH of the plaque, determined with a pH meter. Study (3): A scoring system to assess lesion activity was devised based on the predictive power of the visual appearance of the lesion (ICDAS II system), location of the lesion in a plaque stagnation area and, finally, the tactile feeling, rough/soft or smooth/hard, when running a perio-probe over the lesion. The accuracy was tested in a clinical study of 35 children with 225 lesions/sound surfaces and was validated using the Clinpro impression material for construct validity. Study (1): Intra- and inter-examiner reproducibility was found to be excellent (Kappa-values > 0.82) and the associations strong (Spearmans correlation coefficients > 0.90). Study (2): The Clinpro impression material was found to be acceptable as compared to the results of a pH meter, the combined sensitivity and specificity was 1.63. Study (3): ROC analysis showed that the devised classification system for determining lesion activity had acceptable accuracy (area under curve = 0.84 and the highest combined sum of specificity and sensitivity was 1.67). Thus, it is possible to predict lesion depth and assess the activity of primary coronal caries lesions accurately by using the

  2. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability

    PubMed Central

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J.; Bainbridge, James W.; Gale, David C.; Pierre, Esaie; Krauss, Achim H.P.; Adamson, Peter; Shima, David T.; Ng, Yin-Shan

    2016-01-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. PMID:26188133

  3. Polypoidal Choroidal Vasculopathy in Asians

    PubMed Central

    Wong, Chee Wai; Wong, Tien Y.; Cheung, Chui Ming Gemmy

    2015-01-01

    Age related macular degeneration (AMD) in Asians has been suggested to differ from their Western counterparts in terms of epidemiology, pathogenesis, clinical presentation and treatment. In particular, polypoidal choroidal vasculopathy (PCV) appears to be the predominant subtype of exudative AMD in Asian populations, in contrast to choroidal neovascularization secondary to AMD (CNV-AMD) in Western populations. Epidemiological data on PCV has been largely limited to hospital-based studies and there are currently no data on the incidence of PCV. Similarities and differences in risk factor profile between PCV and CNV-AMD point to some shared pathogenic mechanisms but also differential underlying mechanisms leading to the development of each phenotype. Serum biomarkers such as CRP, homocysteine and matrix metalloproteinases suggest underlying inflammation, atherosclerosis and deranged extracellular matrix metabolism as possible pathogenic mechanisms. In addition, recent advances in genome sequencing have revealed differences in genetic determinants of each subtype. While the standard of care for CNV-AMD is anti-vascular endothelial growth factor (VEGF) therapy, photodynamic therapy (PDT) has been the mainstay of treatment for PCV, although long-term visual prognosis remains unsatisfactory. The optimal treatment for PCV requires further clarification, particularly with different types of anti-VEGF agents and possible benefits of reduced fluence PDT. PMID:26239448

  4. Melissa officinalis Extract Inhibits Laser-Induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Lee, Eun Kyoung; Kim, Young Joo; Kim, Jin Young; Song, Hyun Beom; Yu, Hyeong Gon

    2014-01-01

    Purpose This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated. Methods Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs). Results The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P<0.001), 44.09±12.01 µm in the low-dose group (P = 0.016), and 51.00±12.37 µm in the control group. The proportion of CNV lesions with clinically significant fluorescein leakage was 9.2% in rats treated with high-dose M. officinalis, which was significantly lower than in control rats (53.4%, P<0.001). The levels of VEGF, MMP-2, and MMP-9 were significantly lower in the high-dose group than in the control group. Meanwhile, M. officinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. Conclusions Systemic administration of M. officinalis extract suppressed laser-induced CNV

  5. Choroidal changes observed with enhanced depth imaging optical coherence tomography in patients with mild Graves orbitopathy.

    PubMed

    Özkan, B; Koçer, Ç A; Altintaş, Ö; Karabaş, L; Acar, A Z; Yüksel, N

    2016-07-01

    PurposeTo evaluate the choroidal thickness in patients with Graves orbitopathy (GO) using enhanced depth imaging-optical coherence tomography (EDI-OCT).MethodsThirty-one patients with GO were evaluated prospectively. All subjects underwent ophthalmologic examination including best-corrected visual acuity, intraocular pressure measurement, biomicroscopic, and fundus examination. Choroidal thickness was measured at the central fovea. In addition, visual evoked potential measurement and visual field evaluation were performed.ResultsThe mean choroidal thickness was 377.8±7.4 μ in the GO group, and 334±13.7 μ in the control group. (P=0.004). There was a strong correlation between the choridal thickness and the clinical activity scores (CAS) of the patients (r=0.281, P=0.027). Additionally, there was a correlation between the choroidal thickness and the visual-evoked potential (VEP) P100 latency measurements of the patients (r=0.439, P=0.001).ConclusionsThe results of this study demonstrate that choroid is thicker in patients with GO. The choroidal thickness is also correlated with the CAS and VEP P100 latency measurements in these patients. PMID:27315349

  6. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

    PubMed

    Plumb, Jonnie; McQuaid, Stephen; Mirakhur, Meenakshi; Kirk, John

    2002-04-01

    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. PMID:11958369

  7. Elevated homocysteine levels in suction-induced blister fluid of active vitiligo lesions.

    PubMed

    Anbar, Tag; Zuel-Fakkar, Nehal Mohamed; Matta, Mary Fikry; Arbab, Mai Mohammed Ibrahim

    2016-02-01

    Vitiligo is the most prevalent acquired pigmentary disorder as a result of destruction of melanocytes. Several studies have reported increased serum levels of homocysteine (Hcy) in vitiligo patients which may be the result of decreased Vitamin B12 and folic acid levels. In addition, homocystinuria is associated with pigmentary dilution. On the other hand, other studies reported normal serum homocysteine levels. Our aim was to study the Hcy level in active vitiligo patients both in serum and in suction blister fluid obtained from the lesional skin. A total of 30 patients with active vitiligo of both sexes and 30 healthy volunteers were enrolled in this study. Sera from the blood and from lesional induced bullae were obtained from the patients and controls and were assayed for Hcy by enzyme-linked immunosorbent assay (ELISA). The collected data were analyzed by SPSS version 17. There were no significant differences in the serum levels of Hcy between patients and healthy controls, however, the increase in Hcy level was highly statistically significant in the patients' lesional induced bulla compared to the healthy controls. There was no significant difference in Hcy levels between males and females and between patients with negative or positive family histories of vitiligo. The presence of a high homocysteine level in active vitiligo lesions points to a local event occurring in this lesion, which is not reflected as an increase in the patient's serum level. PMID:26678812

  8. Multimodal Imaging Evaluations of Focal Choroidal Excavations in Eyes with Central Serous Chorioretinopathy

    PubMed Central

    Chen, Zhi-Qing; Wang, Wei

    2016-01-01

    Purpose. To investigate the prevalence and characteristics of focal choroidal excavation (FCE) concurrent with central serous chorioretinopathy (CSC) using multimodal imaging. Methods. This was a retrospective single-institution study. Clinical features and multimodal imaging findings were analyzed in eyes with CSC and FCEs, using imaging methods including optical coherence tomography (OCT), OCT angiography (OCTA), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and multispectral imaging. Results. Seventeen patients (4.8%) with 21 FCEs (19 eyes) were found among 351 consecutive Chinese patients with CSC. Chronic CSC represented 47.1% of those cases. Window defects in 12 lesions identified through FA and hypoautofluorescence in 13 lesions identified through FAF revealed retinal pigment epithelial attenuation. Choroidal hemodynamic disturbances characterized by localized filling defects at the excavation and circumferential hyperperfusion were validated by both ICGA and OCTA, which were similar to the angiographic features of normal chronic CSC. The hyperreflective tissue beneath FCE, observed on B-scan OCT, presented as intensive choroidal flow signals on OCTA. Conclusions. FCE is not uncommon in patients with CSC. Multimodal imaging suggested that the aberrant choroidal circulation might be a contribution factor for leakage from the dysfunctional retinal pigment epithelium at the area of excavation. PMID:27437148

  9. [Histopathologic study of melanoma of the choroid after proton therapy].

    PubMed

    Devouassoux Shishe Boran, M; Grange, J D; Patricot, L M; Adeleine, P; Chauvel, P; Chiquet, C; Vitrey, D; Thivolet Béjui, F

    1997-07-01

    To evaluate irradiation effects on choroidal melanomas, histopathologic findings of 18 eyes whose primary treatment was enucleation were compared to 15 eyes enucleated after proton beam irradiation. Irradiated tumors showed more likely necrosis (p = 0.01) had balloon cells (p = 0.01), and inflammatory infiltrate (p = 0.05). In the irradiated group, the prevalence of tumor blood vessel damage was higher (p = 0.0002) and mitotic figures were fewer (p = 0.01). These findings suggest that proton beam irradiation damages tumor cells and alters the tumor's capacity for cellular reproduction. It damages blood vessels leading to tumor necrosis. It induces an inflammatory response of unknown effects. Radiosensitivity of choroidal melanomas cannot be assessed using conventional histologic methods. However, tumor necrosis, mitotic activity and rate of balloon cells can help to establish tumoral sensitivity to irradiation. PMID:9296578

  10. Regulation of endothelial nitric oxide synthase by PGD(2) in the developing choroid.

    PubMed

    Dumont, I; Hardy, P; Peri, K G; Hou, X; Molotchnikoff, S; Varma, D R; Chemtob, S

    2000-01-01

    We investigated if prostaglandins might regulate the increased choroidal endothelial (e) nitric oxide synthase (NOS) expression in the perinate. Prostaglandins, eNOS mRNA, immunoreactive protein and activity, and nitrite [stable metabolite of nitric oxide (NO)] production were markedly higher in newborn (1 day old) than juvenile (6-8 wk old) pig choroid. Treatment of isolated newborn choroids with the prostaglandin synthase inhibitor ibuprofen for 24 h reduced eNOS mRNA and nitrite production to values in juveniles. This effect was equally observed with the PGD(2) receptor (DP) blocker BW A868C and was prevented by cotreatment with PGD(2) but not other prostaglandins; similar observations were made on NOS activity in vivo. PGD(2) also increased eNOS expression on choroids of juveniles, and this effect was blocked by BW A868C. The manifestation of this upregulation of eNOS by PGD(2) on the control of choroidal vasomotor response was tested by using NO-dependent vasorelaxants, ACh, bradykinin (Bk), and substance P (SP). ACh-, Bk-, and SP-elicited choroidal vasorelaxation was greater in saline-treated newborn than juvenile pigs. Ibuprofen (24 h) decreased ACh-, Bk-, and SP-evoked vasorelaxation in newborns, whereas PGD(2) increased that in juveniles and prevented the ibuprofen-induced attenuated relaxation in newborns; infusion of N(omega)-monomethyl-L-arginine in choroids of those animals treated with PGD(2) reversed the augmented vasorelaxation to ACh, Bk, and SP. Finally, PGD(2)-induced upregulation of NOS in the perinate was also reflected by curtailed choroidal blood flow autoregulatory response to increased perfusion pressure. In conclusion, PGD(2) exhibits a major role in upregulating eNOS expression and activity in the choroid, which in turn results in greater NO-mediated vasorelaxation; a new mechanism for eNOS regulation via DP is hereby disclosed. The relationship between PGD(2) and eNOS in the developing subject provides an explanation for the interactive

  11. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

    PubMed Central

    Li, Y.; Liu, X.; Zhou, T.; Kelley, M.R.; Edwards, P.; Gao, H.; Qiao, X.

    2014-01-01

    The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

  12. Enucleation versus plaque irradiation for choroidal melanoma

    SciTech Connect

    Straatsma, B.R.; Fine, S.L.; Earle, J.D.; Hawkins, B.S.; Diener-West, M.; McLaughlin, J.A.

    1988-07-01

    The Collaborative Ocular Melanoma Study (COMS) is an international, multicenter-controlled study. The organization includes an Executive Committee, Steering Committee, 6 Central Units, 32 Clinical Centers, and a Data and Safety Monitoring Committee. Scientifically, the COMS consists of (1) a randomized trial of patients with medium choroidal melanoma treated with enucleation versus iodine-125 plaque irradiation, (2) a randomized trial of patients with large choroidal melanoma treated with enucleation versus preenucleation external beam irradiation and enucleation, and (3) a prospective observational study of patients with small choroidal melanoma to determine whether a randomized trial of treatment is appropriate. In design and conduct of the COMS, special consideration is given to biostatistics and sample size considerations, iodine-125 plaque irradiation of choroidal melanoma, and coordinated ocular melanoma research. Recruitment is in progress. However, the pool of eligible patients is limited and the COMS needs the continued support and cooperation of ophthalmologists throughout the United States and Canada.

  13. Choroidal physiology and primary angle closure disease.

    PubMed

    Zhang, Xiulan; Wang, Wei; Aung, Tin; Jonas, Jost B; Wang, Ningli

    2015-01-01

    Primary angle closure disease (PACD), prevalent in Asian countries, is generally associated with a shallower anterior chamber, a shorter axial length, thicker lens, hyperopia, and female sex. Other physiologic factors, however, may be important, especially with regard to triggering acute primary angle closure. Thickening of the choroid has been demonstrated in untreated and treated, acute and chronic PACD eyes. Recently, there has been growing interest in studying the role of the choroid in the pathophysiology of PACD. The emergence of new imaging technology such as the enhanced depth imaging mode of spectral-domain optical coherence tomography and swept-source optical coherence tomography has contributed to understanding PACD pathologies. We summarize the functions of the choroid and choroidal changes in the pathogenesis of PACD, and discuss potential future developments. PMID:26164737

  14. Pediatric genetic macular and choroidal diseases

    PubMed Central

    Bergman, Mica Y.; Nallasamy, Sudha

    2014-01-01

    Genetic diseases of the macula and choroid have various inheritance patterns and varying degrees of impact on vision. Herein, we review the literature including most recent advances in the understanding of the genetics of these diseases. Although many of these disorders have limited treatment options, knowledge of inheritance patterns can aid in early detection and with close monitoring can help the ophthalmologist preserve as much vision as possible (for example with early treatment of choroidal neovascularization).

  15. Determinant Factors of Untreated Dental Caries and Lesion Activity in Preschool Children Using ICDAS

    PubMed Central

    Pinto-Sarmento, Tássia Cristina de Almeida; Abreu, Mauro Henrique; Gomes, Monalisa Cesarino; Costa, Edja Maria Melo de Brito; Martins, Carolina Castro; Granville-Garcia, Ana Flávia; Paiva, Saul Martins

    2016-01-01

    The aim of the present study was to investigate determinant factors associated with the presence of dental caries and lesion activity in preschool children. A population-based, cross-sectional study was carried out with 843 children of aged three to five years enrolled at public and private preschools in the city of Campina Grande, Brazil. A questionnaire addressing socio-demographic data and oral health care was self-administered by parents/caregivers. Three dentists previously calibrated examined the children for the diagnosis of dental caries and lesion activity using the International Caries Detection and Assessment System (ICDAS). Nutritional status was evaluated based on the body mass index. Logistic regression analysis for complex samples was performed (α = 5%). The prevalence of dental caries was 66.3%. Among the children with caries, 88.0% had active lesions. Dental caries was more prevalent in girls (OR = 1.53, 95%CI: 1.05–2.23), in children from families with a monthly household income ≤US$312.50 (OR = 2.38, 95%CI: 1.65–3.43) and those whose mothers had up to eight years of schooling (OR = 1.55, 95%CI: 1.07–2.23). Lesion activity was significantly associated with mother’s schooling ≤ 8 years (OR = 2.15, 95%CI: 1.15–4.00). The prevalence rates of dental caries and lesion activity were high and mainly associated with a lower socioeconomic status and mother’s schooling. PMID:26900846

  16. Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS.

    PubMed

    Kunis, Gilad; Baruch, Kuti; Miller, Omer; Schwartz, Michal

    2015-04-22

    Amyotrophic lateral sclerosis (ALS) is a devastating fatal motor neuron disease, for which there is currently no cure or effective treatment. In this disease, local neuroinflammation develops along the disease course and contributes to its rapid progression. In several models of CNS pathologies, circulating immune cells were shown to display an indispensable role in the resolution of the neuroinflammatory response. The recruitment of such cells to the CNS involves activation of the choroid plexus (CP) of the brain for leukocyte trafficking, through a mechanism that requires IFN-γ signaling. Here, we found that in the mutant SOD1(G93A) (mSOD1) mouse model of ALS, the CP does not support leukocyte trafficking during disease progression, due to a local reduction in IFN-γ levels. Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma. The immunization resulted in the attenuation of disease progression and an increased life expectancy of the mSOD1 mice. Collectively, our results demonstrate that recruitment of immunoregulatory cells to the diseased spinal cord in ALS, needed for fighting off the pathology, can be enhanced by transiently boosting peripheral immunity to myelin antigens. PMID:25904790

  17. The association between sterilizing activity and drug distribution into tuberculosis lesions

    PubMed Central

    Prideaux, Brendan; Via, Laura E.; Zimmerman, Matthew D.; Eum, Seokyong; Sarathy, Jansy; O’Brien, Paul; Chen, Chao; Kaya, Firat; Weiner, Danielle M.; Chen, Pei-Yu; Song, Taeksun; Lee, Myungsun; Shim, TaeSun; Cho, Jeong Su; Kim, Wooshik; Cho, Sang Nae; Olivier, Kenneth N.; Barry, Clifton E.; Dartois, Véronique

    2015-01-01

    Finding new treatment-shortening antibiotics to improve cure rates and curb the alarming emergence of drug resistance is the major objective of tuberculosis (TB) drug development. Using a MALDI mass spectrometry imaging suite in a biosafety containment facility, we show that the key sterilizing drugs rifampicin and pyrazinamide efficiently penetrate the sites of TB infection in lung lesions. Rifampicin even accumulates in necrotic caseum, a critical lesion site where persisting tubercle bacilli reside1. In contrast, moxifloxacin which is active in vitro against persisters, a sub-population of Mycobacterium tuberculosis that persists in specific niches under drug pressure, and achieved treatment shortening in mice2, does not diffuse well in caseum, concordant with its failure to shorten therapy in recent clinical trials. We also suggest that such differential spatial distribution and kinetics of accumulation in lesions may create temporal and spatial windows of monotherapy in specific niches, allowing the gradual development of multidrug resistant TB. We propose an alternative working model to prioritize new antibiotic regimens based on quantitative and spatial distribution of TB drugs in the major lesion types found in human lungs. The finding that lesion penetration contributes to treatment outcome has wide implications for TB. PMID:26343800

  18. Choroid Sprouting Assay: An Ex Vivo Model of Microvascular Angiogenesis

    PubMed Central

    Shao, Zhuo; Friedlander, Mollie; Hurst, Christian G.; Cui, Zhenghao; Pei, Dorothy T.; Evans, Lucy P.; Juan, Aimee M.; Tahir, Houda; Duhamel, François; Chen, Jing; Sapieha, Przemyslaw; Chemtob, Sylvain; Joyal, Jean-Sébastien; Smith, Lois E. H.

    2013-01-01

    Angiogenesis of the microvasculature is central to the etiology of many diseases including proliferative retinopathy, age-related macular degeneration and cancer. A mouse model of microvascular angiogenesis would be very valuable and enable access to a wide range of genetically manipulated tissues that closely approximate small blood vessel growth in vivo. Vascular endothelial cells cultured in vitro are widely used, however, isolating pure vascular murine endothelial cells is technically challenging. A microvascular mouse explant model that is robust, quantitative and can be reproduced without difficulty would overcome these limitations. Here we characterized and optimized for reproducibility an organotypic microvascular angiogenesis mouse and rat model from the choroid, a microvascular bed in the posterior of eye. The choroidal tissues from C57BL/6J and 129S6/SvEvTac mice and Sprague Dawley rats were isolated and incubated in Matrigel. Vascular sprouting was comparable between choroid samples obtained from different animals of the same genetic background. The sprouting area, normalized to controls, was highly reproducible between independent experiments. We developed a semi-automated macro in ImageJ software to allow for more efficient quantification of sprouting area. Isolated choroid explants responded to manipulation of the external environment while maintaining the local interactions of endothelial cells with neighboring cells, including pericytes and macrophages as evidenced by immunohistochemistry and fluorescence-activated cell sorting (FACS) analysis. This reproducible ex vivo angiogenesis assay can be used to evaluate angiogenic potential of pharmacologic compounds on microvessels and can take advantage of genetically manipulated mouse tissue for microvascular disease research. PMID:23922736

  19. Choroid plexus papilloma with a hyperdiploid karyotype

    SciTech Connect

    Roland, B.; Pinto, A.

    1994-09-01

    An 11-month-old male underwent surgery for a choroid plexus neoplasm, which on histologic examination was diagnosed as a benign papilloma. Chromosome analysis showed a karyotype of 55,XY,+7+7,+8,+9,+12,+12,+15,+20,+21 in all 20 metaphases analyzed. This is only the third benign choroid plexus papilloma that has been karyotyped, with the others being normal and hypodiploid (33 chromosomes). Three malignant choroid plexus carcinomas have also been analyzed, two with normal karyotypes and one hypodiploid (34 - 35 chromosomes). The two hypoidiploid neoplasms lack chromosomes 2, 3, 4, 5, 10, 13, 14, 17 and 18. Since the chromosomes that are lost in the hypodiploid neoplasms are different from the chromosomes gained in our tumor, it appears that the dosage of specific chromosomes is important in the origin of choroid plexus neoplasms. Benign choroid plexus papillomas can be difficult to differentiate from choroid plexus carcinomas. With the data available so far, it does not appear that cytogenetics can assist in making the diagnosis.

  20. Nitric oxide decreases intestinal haemorrhagic lesions in rat anaphylaxis independently of mast cell activation

    PubMed Central

    Tavares, J. Carvalho; Moreno, A.

    1997-01-01

    The purpose of this study is to assess the role of nitric oxide (NO) in the intestinal lesions of passive anaphylaxis, since this experimental model resembles necrotizing enterocolitis. Sprague-Dawley rats were sensitized with IgE anti-dinitrophenol monoclonal antibody. Extravasation of protein-rich plasma and haemorrhagia were measured in the small intestine. Plasma histamine was measured to assess mast cell activation. The effect of exogenous NO on the lesions was assessed by using two structurally unrelated NO-donors: sodium nitroprusside and S-nitroso-Nacetyl-penicillamine (SNAP). An increased basal production of NO was observed in cells taken after anaphylaxis, associated with a reduced response to platelet-activating factor, interleukin 1beta, and IgE/DNP-bovine serum albumin complexes. The response to bacterial lipopolysaccharide and dibutyryl cyclic adenosine monophosphate (AMP) was enhanced 24 h after challenge, but at earlier times was not significantly different from that observed in controls. Treatment with either sodium nitroprusside or SNAP produced a significant reduction of the haemorrhagic lesions, which are a hallmark of rat anaphylaxis. The extravasation of protein-rich plasma was not influenced by NO-donors. The increase of plasma histamine elicited by the anaphylactic challenge was not influenced by SNAP treatment. NO-donors protect intestinal haemorrhagic lesions of rat anaphylaxis by a mechanism apparently independent of mast cell histamine release. PMID:18472830

  1. Enzymatic activity of Microsporum canis and Trichophyton mentagrophytes from breeding rabbits with and without skin lesions.

    PubMed

    Cafarchia, Claudia; Figueredo, Luciana A; Coccioli, Carmela; Camarda, Antonio; Otranto, Domenico

    2012-01-01

    Microsporum canis and Trichophyton mentagrophytes are zoophilic dermatophytes which can cause skin infections in animals and humans. The clinical expression of this infection strongly varies depending on host, fungal species as well as enzyme production. No comparative studies are available on the enzymatic activities of M. canis and T. mentagrophytes isolated from breeding rabbits. Thus, the aim of this work was to assess the capability of M. canis and T. mentagrophytes isolated from rabbits both with and without lesions in producing different enzymes. The relationship of dermatophyte enzymatic activities and presence/absence of skin lesions has also been investigated. A total of 260 isolates of T. mentagrophytes and 25 isolates of M. canis sampled both from healthy and lesioned skin of rabbits, as well as from air samples of positive farms were examined. The results showed that T. mentagrophytes and M. canis from rabbits produce different enzymes. However, only elastase and gelatinase were linked to the appearance of lesions in T. mentagrophytes infections, whereas lipase in those by M. canis. PMID:22175244

  2. Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters

    PubMed Central

    Richardson, Samantha J.; Wijayagunaratne, Roshen C.; D'Souza, Damian G.; Darras, Veerle M.; Van Herck, Stijn L. J.

    2015-01-01

    Thyroid hormones are key players in regulating brain development. Thus, transfer of appropriate quantities of thyroid hormones from the blood into the brain at specific stages of development is critical. The choroid plexus forms the blood-cerebrospinal fluid barrier. In reptiles, birds and mammals, the main protein synthesized and secreted by the choroid plexus is a thyroid hormone distributor protein: transthyretin. This transthyretin is secreted into the cerebrospinal fluid and moves thyroid hormones from the blood into the cerebrospinal fluid. Maximal transthyretin synthesis in the choroid plexus occurs just prior to the period of rapid brain growth, suggesting that choroid plexus-derived transthyretin moves thyroid hormones from blood into cerebrospinal fluid just prior to when thyroid hormones are required for rapid brain growth. The structure of transthyretin has been highly conserved, implying strong selection pressure and an important function. In mammals, transthyretin binds T4 (precursor form of thyroid hormone) with higher affinity than T3 (active form of thyroid hormone). In all other vertebrates, transthyretin binds T3 with higher affinity than T4. As mammals are the exception, we should not base our thinking about the role of transthyretin in the choroid plexus solely on mammalian data. Thyroid hormone transmembrane transporters are involved in moving thyroid hormones into and out of cells and have been identified in many tissues, including the choroid plexus. Thyroid hormones enter the choroid plexus via thyroid hormone transmembrane transporters and leave the choroid plexus to enter the cerebrospinal fluid via either thyroid hormone transmembrane transporters or via choroid plexus-derived transthyretin secreted into the cerebrospinal fluid. The quantitative contribution of each route during development remains to be elucidated. This is part of a review series on ontogeny and phylogeny of brain barrier mechanisms. PMID:25784853

  3. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases.

    PubMed

    Mello, Patrícia Correa de; Berensztejn, Patricia; Brasil, Oswaldo Ferreira Moura

    2016-01-01

    We report enhanced depth imaging optical coherence tomography (EDI-OCT) features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction. PMID:27463635

  4. GLENOHUMERAL MUSCLE ACTIVATION DURING PROVOCATIVE TESTS DESIGNED TO DIAGNOSE SUPERIOR LABRUM ANTERIOR-POSTERIOR LESIONS

    PubMed Central

    Wood, Vanessa J.C.; Sabick, Michelle B.; Pfeiffer, Ron P.; Kuhlman, Seth M.; Christensen, Jason H.; Curtin, Michael J.

    2012-01-01

    Background Despite considerable medical advances, arthroscopy remains the only definitive means of Superior Labrum Anterior-Posterior (SLAP) lesion diagnosis. Natural shoulder anatomic variants limit the reliability of radiographic findings and clinical evaluations are not consistent. Accurate clinical diagnostic techniques would be advantageous due to the invasiveness, patient risk, and financial cost associated with arthroscopy. Purpose The purpose was to examine the behavior of the joint stabilizing muscles in provocative tests for SLAP lesions. Electromyography was used to characterize the muscle behavior, with particular interest in the long head biceps brachii (LHBB), as activation of the long head and subsequent tension in the biceps tendon should, based on related research, elicit labral symptoms in SLAP lesion patients. Study Design Controlled Laboratory Study Methods Volunteers (N=21) without a history of shoulder pathology were recruited. The tests analyzed were Active Compression, Speed's, Pronated Load, Biceps I, Biceps II, Resisted Supination External Rotation, and Yergason's. Tests were performed with a dynamometer to improve reproducibility. Muscle activity was recorded for the long and short heads of the biceps brachii, anterior deltoid, pectoralis major, latissimus dorsi, infraspinatus, and supraspinatus. Muscle behavior for each test was characterized by peak activation and proportion of muscle activity. Results Speed's, Active Compression Palm-Up, Bicep I and Bicep II, produced higher long head activations. Resisted Supination External Rotation, Bicep I, Bicep II, and Yergason's, produced a higher LHBB proportion. Conclusion Bicep I, and Bicep II elicited promising long head behavior (high activation and selectivity). Speed's and Active Compression Palm-Up elicited higher activation of the LHBB , and Resisted Supination and Yergason's elicited selective LHBB activity. These top performing tests utilize a unique range of test variables that may

  5. Polymer fraction of Aloe vera exhibits a protective activity on ethanol-induced gastric lesions.

    PubMed

    Park, Chul-Hong; Nam, Dong-Yoon; Son, Hyeong-U; Lee, Si-Rim; Lee, Hyun-Jin; Heo, Jin-Chul; Cha, Tae-Yang; Baek, Jin-Hong; Lee, Sang-Han

    2011-04-01

    For centuries, Aloe has been used as a herbal plant remedy against skin disorders, diabetes, and for its cardiac stimulatory activity. Here, we examined the gastroprotective effects of an Aloe vera polymer fraction (Avpf; molecular weight cut-off ≥50 kDa; 150 mg/kg body weight, p.o.) on an ethanol-induced gastric lesion mouse model. Mice pre-treated with Avpf had significantly fewer gastric lesions than their respective controls. To further examine the potential mechanism underlying this effect, we used reverse transcription-polymerase chain reaction to examine nitric oxide synthase and matrix metalloproteinase (MMP)mRNA expression on tissues from gastric lesions. Our results revealed that the mRNA expressions of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) were each reduced by ~50% in Avpf-treated mice vs. the controls, whereas, the mRNA expression levels of endothelial nitric oxide synthase remained unchanged. MMP-9, an index for gastric lesions, also alleviated the ethanol-treated gastric ulceration during Avpf treatment. These findings collectively suggest that Avpf significantly protects the gastric mucosa against ethanol-induced gastric damage, at least in part, by decreasing mRNA expression levels of not only iNOS and nNOS, but also MMP-9. PMID:21286662

  6. Reduced cytochrome oxidase activity in the retrosplenial cortex after lesions to the anterior thalamic nuclei.

    PubMed

    Mendez-Lopez, Magdalena; Arias, Jorge L; Bontempi, Bruno; Wolff, Mathieu

    2013-08-01

    The anterior thalamic nuclei (ATN) make a critical contribution to hippocampal system functions. Growing experimental work shows that the effects of ATN lesions often resemble those of hippocampal lesions and both markedly reduce the expression of immediate-early gene markers in the retrosplenial cortex, which still appears normal by standard histological means. This study shows that moderate ATN damage was sufficient to produce severe spatial memory impairment as measured in a radial-arm maze. Furthermore, ATN rats exhibited reduced cytochrome oxidase activity in the most superficial cortical layers of the granular retrosplenial cortex, and, to a lesser extent, in the anterior cingulate cortex. By contrast, no change in cytochrome oxidase activity was observed in other limbic cortical regions or in the hippocampal formation. Altogether our results indicate that endogenous long-term brain metabolic capacity within the granular retrosplenial cortex is compromised by even limited ATN damage. PMID:23660649

  7. Antifungal Activity of Plant Extracts against Candida Species from Oral Lesions

    PubMed Central

    Prabhakar, K.; Kumar, L. Sathish; Rajendran, S.; Chandrasekaran, M.; Bhaskar, K.; Sajit Khan, A. K.

    2008-01-01

    Seventy five patients with oral lesions attending the different departments of Rajah Muthiah Medical College and Hospital, Annamalai University were screened for Candida. Forty six (61.3%) Candida strains were isolated from the oral lesions. Of the 46 Candida strains, Candida albicans accounted for 35 (76.08%), Candida glabrata for 5 (10.86%), Candida tropicalis and Candida krusei for 2 (4.34%) each and Candida parapsilosis and Candida guilliermondii for one (2.17%) each. Antifungal activity of ethanol extracts of five plant species that included Syzygium jambolanum, Cassia siamea, Odina wodier, Momordica charantia and Melia azedarach and two algal species, Sargassum wightii and Caulerpa scalpelliformis were tested against 25 isolated strains by disc diffusion method. Antifungal activity was observed at 100 mg/ml for Syzygium jambolanum, Cassia siamea and Caulerpa scalpelliformis and at 10 mg/ml for Sargassum wightii. PMID:21369447

  8. Proteasome activity is required for the initiation of precancerous pancreatic lesions.

    PubMed

    Furuyama, Takaki; Tanaka, Shinji; Shimada, Shu; Akiyama, Yoshimitsu; Matsumura, Satoshi; Mitsunori, Yusuke; Aihara, Arihiro; Ban, Daisuke; Ochiai, Takanori; Kudo, Atsushi; Fukamachi, Hiroshi; Arii, Shigeki; Kawaguchi, Yoshiya; Tanabe, Minoru

    2016-01-01

    Proteasome activity is significantly increased in advanced cancers, but its role in cancer initiation is not clear, due to difficulties in monitoring this process in vivo. We established a line of transgenic mice that carried the ZsGreen-degron(ODC) (Gdeg) proteasome reporter to monitor the proteasome activity. In combination with Pdx-1-Cre;LSL-Kras(G12D) model, proteasome activity was investigated in the initiation of precancerous pancreatic lesions (PanINs). Normal pancreatic acini in Gdeg mice had low proteasome activity. By contrast, proteasome activity was increased in the PanIN lesions that developed in Gdeg;Pdx-1-Cre;LSL-Kras(G12D) mice. Caerulein administration to Gdeg;Pdx-1-Cre;LSL-Kras(G12D) mice induced constitutive elevation of proteasome activity in pancreatic tissues and accelerated PanIN formation. The proteasome inhibitor markedly reduced PanIN formation in Gdeg;Pdx-1-Cre;LSL-Kras(G12D) mice (P = 0.001), whereas it had no effect on PanIN lesions that had already formed. These observations indicated the significance of proteasome activity in the initiation of PanIN but not the maintenance per se. In addition, the expressions of pERK and its downstream factors including cyclin D1, NF-κB, and Cox2 were decreased after proteasome inhibition in PanINs. Our studies showed activation of proteasome is required specifically for the initiation of PanIN. The roles of proteasome in the early stages of pancreatic carcinogenesis warrant further investigation. PMID:27244456

  9. Proteasome activity is required for the initiation of precancerous pancreatic lesions

    PubMed Central

    Furuyama, Takaki; Tanaka, Shinji; Shimada, Shu; Akiyama, Yoshimitsu; Matsumura, Satoshi; Mitsunori, Yusuke; Aihara, Arihiro; Ban, Daisuke; Ochiai, Takanori; Kudo, Atsushi; Fukamachi, Hiroshi; Arii, Shigeki; Kawaguchi, Yoshiya; Tanabe, Minoru

    2016-01-01

    Proteasome activity is significantly increased in advanced cancers, but its role in cancer initiation is not clear, due to difficulties in monitoring this process in vivo. We established a line of transgenic mice that carried the ZsGreen-degronODC (Gdeg) proteasome reporter to monitor the proteasome activity. In combination with Pdx-1-Cre;LSL-KrasG12D model, proteasome activity was investigated in the initiation of precancerous pancreatic lesions (PanINs). Normal pancreatic acini in Gdeg mice had low proteasome activity. By contrast, proteasome activity was increased in the PanIN lesions that developed in Gdeg;Pdx-1-Cre;LSL-KrasG12D mice. Caerulein administration to Gdeg;Pdx-1-Cre;LSL-KrasG12D mice induced constitutive elevation of proteasome activity in pancreatic tissues and accelerated PanIN formation. The proteasome inhibitor markedly reduced PanIN formation in Gdeg;Pdx-1-Cre;LSL-KrasG12D mice (P = 0.001), whereas it had no effect on PanIN lesions that had already formed. These observations indicated the significance of proteasome activity in the initiation of PanIN but not the maintenance per se. In addition, the expressions of pERK and its downstream factors including cyclin D1, NF-κB, and Cox2 were decreased after proteasome inhibition in PanINs. Our studies showed activation of proteasome is required specifically for the initiation of PanIN. The roles of proteasome in the early stages of pancreatic carcinogenesis warrant further investigation. PMID:27244456

  10. Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions

    PubMed Central

    Kimberlin, David W.; Baley, Jill; Brady, Michael T.; Byington, Carrie L.; Davies, H. Dele; Edwards, Kathryn M.; Glode, Mary P.; Jackson, Mary Anne; Keyserling, Harry L.; Maldonado, Yvonne A.; Murray, Dennis L.; Orenstein, Walter A.; Schutze, Gordon E.; Willoughby, Rodney E.; Zaoutis, Theoklis E.; Papile, Lu-Ann; Bhutani, Vinod K.; Carlo, Waldemar A.; Cummings, James; Kumar, Praveen; Polin, Richard A.; Tan, Rosemarie C.; Wang, Kasper S.; Watterberg, Kristi L.

    2013-01-01

    Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother’s previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery. PMID:23359576

  11. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions.

    PubMed

    Kimberlin, David W; Baley, Jill

    2013-02-01

    Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother's previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery. PMID:23359576

  12. Failure of choroidal melanoma to respond to helium ion therapy

    SciTech Connect

    Char, D.H.; Crawford, J.B.; Castro, J.R.; Woodruff, K.H.

    1983-02-01

    Helium ion irradiation is a promising alternative therapy for choroidal melanoma. In short-term follow-up (less than 5 years), more than 90% (18/19) of treated patients demonstrated tumor regression. Researchers had to enucleate five eyes after helium ion therapy either because of continued tumor growth (four patients) or other complications (one patient). Two melanomas continued to grow and seemed to be radioresistant. In two other tumors it retrospectively seemed that the entire lesion was not inside the radiation field. In one patient total retinal detachment and glaucoma developed; enucleation was performed because of a painful eye. Metastatic disease developed in no patients. The treatment failures emphasize that there are a number of unresolved issues regarding the use of charged-particle irradiation in the treatment of melanoma. Further studies must be performed to answer these questions and better delineate the use of these newer forms of therapy.

  13. [Magnetic resonance tomography in ophthalmology. I. Choroid melanoma].

    PubMed

    Seiler, T; Bende, T; Schilling, A; Wollensak, J

    1987-09-01

    The value of magnetic resonance tomography (MRT) for the diagnosis of choroidal melanomas is illustrated with reference to 26 cases. The geometric dimensions of the tumors are in good agreement with findings obtained by ultrasonography. The relaxation time T2 varies between 85 and 120 msec in contrast to 145-210 msec in subretinal hemorrhages and 190-400 msec in secondary retinal detachments. In contrast to A-scan a differential diagnosis is possible even with lesions less than 1.5 mm in prominence. In solutions of melanin the relaxation time T2 decreases with increasing melanin concentration. This leads to an interpretation that the pigment content of the melanoma is responsible for the relatively short relaxation times. Thus, the relaxation time T2 is a useful factor in predicting metastasis. PMID:3316814

  14. The Dynamic Behavior of the Early Dental Caries Lesion in Caries-active Adults and Implications

    PubMed Central

    Brown, J P; Amaechi, B T; Bader, J D; Shugars, D; Vollmer, W M; Chen, C; Gilbert, G H; Esterberg, E J

    2015-01-01

    Objective To describe the full range of behavior of the visible, non-cavitated, early caries lesion in caries-active adults with substantial fluoride exposure, and to consider implications. Methods The data were from the Xylitol for Adult Caries Trial (X-ACT), collected annually for 33 months using condensed ICDAS caries threshold criteria. Individual tooth surfaces having a non-cavitated caries lesion were included and the Patterns of transition to each subsequent annual clinical examination to sound, non-cavitated or cavitated, filled or crowned were determined. The resulting sets of Patterns for an individual tooth surface, looking forward from its first appearance as a non-cavitated lesion, were combined into one of four behavior Profiles classified as Reversing, Stable, Oscillating or continuously Progressing, or were excluded if not part of the caries continuum. The distributions of Profile types were assessed using the Rao-Scott Chi square test, which adjusts for clustering of tooth surfaces within teeth. Results Inter-and intra-examiner Kappa scores demonstrated acceptable calibration at baseline and annually. 8084 tooth surfaces from 543 subjects were included. The distribution of Profile types differed significantly between coronal and root surfaces. Overall two-thirds of all coronal non-cavitated lesions were first seen at baseline, half Reversed, over a fifth were Stable, 15% Oscillated and only 8.3% progressed to cavitation, filled or crowned in 33 months or less. (6.3% consistently Progressed plus 2.0% inconsistently, a subset of Oscillating, which oscillated before progressing to cavitation). Approximal, smooth and occlusal coronal surfaces each were significantly different in their individual distributions of Profile types. Xylitol showed no significant and consistent effect on this distribution by tooth surface type. This was in keeping with the X-ACT Trial’s lack of effect of xylitol at the non-cavitated plus cavitated lesion thresholds combined

  15. Choroidal thickness changes with photodynamic therapy for a diffuse choroidal hemangioma in Sturge–Weber syndrome.

    PubMed

    Cacciamani, Andrea; Scarinci, Fabio; Parravano, Mariacristina; Giorno, Paola; Varano, Monica

    2014-10-01

    The aim of this study was to evaluate the choroidal thickness (CT) changes associated with visual function following photodynamic therapy (PDT) for a diffuse choroidal hemangioma in Sturge–Weber syndrome. We report a case of Sturge–Weber syndrome and symptomatic serous retinal detachment (SRD) with diffuse choroidal hemangioma treated with PDT. Visual acuity (VA), macular sensitivity measured by means of MP1 microperimeter (Nidek Technologies, Padova, Italy), retinal and CT, measured by means of enhanced depth optical coherence tomography (EDI–OCT, Spectralis, Heidelberg Engineering, Heidelberg, Germany) were analyzed at baseline, 3 and 12 months follow-up.After the PDT VA and macular sensitivity improved.The OCT examination showed the resolution of SRD. The choroid was measured after PDT using EDI–OCT. At baseline, the subfoveal CT showed a progressive thickness reduction from 251 to 83 lm during follow-up. To our knowledge, this is the first report of CT changes after PDT for a diffuse choroidal hemangioma in Sturge–Weber syndrome in a longterm follow-up. The CT measurement represents a potential parameter to better follow choroidal hemangiomas and their response to treatment. However,the long-term choroidal changes should be carefully taken into account. PMID:24658736

  16. Increased contrast enhancing lesion activity in relapsing–remitting multiple sclerosis migraine patients☆

    PubMed Central

    Graziano, Elliot; Hagemeier, Jesper; Weinstock-Guttman, Bianca; Ramasamy, Deepa P.; Zivadinov, Robert

    2015-01-01

    Background and objectives While the literature supports the idea that multiple sclerosis (MS) and migraine are related, the exact mechanism(s) of this association is not well understood. Observations of increased contrast enhancing (CE) lesion activity in individual MS patients suffering from migraine prompted us to determine a relationship between migraine and MRI outcomes in a large cohort of MS patients. Methods We included 509 MS and 64 clinically isolated syndrome (CIS) patients and 251 age- and sex-matched healthy individuals (HIs) who obtained 3 T MRI and were assessed for history of migraine. Number and volume of T2, T1 and CE lesions and brain volume measures were determined. The MRI findings were analyzed adjusting for key covariates and correcting for multiple comparisons. Results More MS (22.2%) and CIS (17.2%) patients had migraine, compared to HIs (14.6%, p = 0.067). More MS patients with migraine presented with CE lesions compared to those without (35.4% vs. 23.7%, p = 0.013). MS migraine patients had significantly increased number (p = 0.019) and volume (p = 0.022) of CE lesions compared to those without. In the regression analysis, MS migraine patients had an increased number of CE lesions (B = 1.242, p = 0.001), specifically those with relapsing–remitting disease course (B = 1.377, p = 0.001). No significant association of other MRI measures and migraine was found in MS and CIS patients or in HIs. Conclusions Our findings suggest an increased inflammatory pathobiology in MS patients with migraine headaches requiring possibly more frequent MRIs and also more efficient anti-inflammatory treatment. PMID:26448911

  17. Expression of regulatory proteins in choroid plexus changes in early stages of Alzheimer disease.

    PubMed

    Krzyzanowska, Agnieszka; García-Consuegra, Inés; Pascual, Consuelo; Antequera, Desiree; Ferrer, Isidro; Carro, Eva

    2015-04-01

    Recent studies indicate that the choroid plexus has important physiologic and pathologic roles in Alzheimer disease (AD). To obtain additional insight on choroid plexus function, we performed a proteomic analysis of choroid plexus samples from patients with AD stages I to II (n = 16), III to IV (n = 16), and V to VI (n = 11) and 7 age-matched control subjects. We used 2-dimensional differential gel electrophoresis coupled with mass spectrometry to generate a complete picture of changes in choroid plexus protein expression occurring in AD patients. We identified 6 proteins: 14-3-3 β/α, 14-3-3 ε, moesin, proteasome activator complex subunit 1, annexin V, and aldehyde dehydrogenase, which were significantly regulated in AD patient samples (p < 0.05, >1.5-fold variation in expression vs control samples). These proteins are implicated in major physiologic functions including mitochondrial dysfunction and apoptosis regulation. These findings contribute additional significance to the emerging importance of molecular and functional changes of choroid plexus function in the pathophysiology of AD. PMID:25756589

  18. Transmigration of macrophages across the choroid plexus epithelium in response to the feline immunodeficiency virus

    PubMed Central

    Meeker, Rick B.; Bragg, D. C.; Poulton, Winona; Hudson, Lola

    2013-01-01

    Although lentiviruses such as human, feline and simian immunodeficiency viruses (HIV, FIV, SIV) rapidly gain access to cerebrospinal fluid (CSF), the mechanisms that control this entry are not well understood. One possibility is that the virus may be carried into the brain by immune cells that traffic across the blood–CSF barrier in the choroid plexus. Since few studies have directly examined macrophage trafficking across the blood–CSF barrier, we established transwell and explant cultures of feline choroid plexus epithelium and measured trafficking in the presence or absence of FIV. Macrophages in co-culture with the epithelium showed significant proliferation and robust trafficking that was dependent on the presence of epithelium. Macrophage migration to the apical surface of the epithelium was particularly robust in the choroid plexus explants where 3-fold increases were seen over the first 24 h. Addition of FIV to the cultures greatly increased the number of surface macrophages without influencing replication. The epithelium in the transwell cultures was also permissive to PBMC trafficking, which increased from 17 to 26% of total cells after exposure to FIV. Thus, the choroid plexus epithelium supports trafficking of both macrophages and PBMCs. FIV significantly enhanced translocation of macrophages and T cells indicating that the choroid plexus epithelium is likely to be an active site of immune cell trafficking in response to infection. PMID:22281685

  19. AMPHETAMINE-, SCOPOLAMINE-, AND CAFFEINE-INDUCED LOCOMOTOR ACTIVITY FOLLOWING 6-HYDROXYDOPAMINE LESIONS OF THE MESOLIMBIC DOPAMINE SYSTEM

    EPA Science Inventory

    As previously reported, 6-hydroxydopamine (6-OHDA) lesions to the region of the nucleus accumbens blocked the locomotor activation induced by low doses of d-amphetamine, and produced a supersensitive locomotor response to the dopamine (DA) agonist, apomorphine. This same lesion, ...

  20. Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions

    PubMed Central

    Roth, Christian L.; D’Ambrosio, Gabrielle; Elfers, Clinton

    2016-01-01

    Background Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. In this study, a hyperphagic rat model of combined medial hypothalamic lesions (CMHL) was used to test which specific inflammatory molecules are involved. Methods In order to target specific homeostatic medial hypothalamic nuclei (arcuate, ventromedial, and dorsomedial nuclei), male Sprague-Dawley rats (age of 8 weeks, ~250 g body weight) received four electrolytic lesions or sham surgery. Post-surgery food intake and weight changes were tracked and hypothalamic gene expression for inflammatory molecules as well as anorexigenic peptide oxytocin 7 days and 7 months post-surgery were tested. Results Seven days post-surgery, average food intake increased by 23%, and body weight gain had increased by 68%. Toll-like 4 receptor/nuclear factor–κB (TLR4/NF–κB)—pathway was specifically activated in the mediobasal hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-α, 10-fold higher interleukin (IL) 1-β mRNA levels, and higher expression of suppression of cytokine signaling (SOCS) 3, while oxytocin mRNA levels were significantly reduced in CMHL rats versus sham surgery rats 7 days post-surgery. At 7 months, inflammation was less stimulated in MBH of CMHL rats compared to 7 days post-surgery and SOCS 3 as well as oxytocin mRNA levels were comparable between the two groups. Conclusion Medial hypothalamic lesions are associated with strong post-surgery hyperphagia and activation of TLR4/NF–κB—pathway as well as reduced expression of oxytocin in the hypothalamus.

  1. Vitreous histocytology of primary choroidal malignant melanoma.

    PubMed

    Traboulsi, E I; Jalkh, A E; Frangieh, G T; Tomb, J

    1987-02-01

    The cytomorphologic findings of a vitrectomy specimen from the right eye of an 80-year-old woman with an unsuspected primary choroidal malignant melanoma are described. The patient had undergone a closed vitrectomy because of chronic vitreous hemorrhage. Histocytology of the vitreous fluid specimens revealed melanoma cells of variable shape and size (from 30-150 microns) with eccentric nuclei. Many of these cells were binucleated or multinucleated with small, uniform, evenly dispersed intracytoplasmic melanin granules. The histocytologic findings together with the postoperative tumor characteristics by ultrasonography and fluorescein angiography suggested the diagnosis of choroidal malignant melanoma. PMID:3566022

  2. The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation.

    PubMed

    Jennings, Katie A; Platt, Nicola J; Cragg, Stephanie J

    2015-10-01

    Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

  3. The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

    PubMed Central

    Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

    2015-01-01

    Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

  4. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model.

    PubMed

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

  5. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model

    PubMed Central

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

  6. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report.

    PubMed

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim; Hemati, Karim

    2015-05-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

  7. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report

    PubMed Central

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim

    2015-01-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

  8. Enlargement of choroid plexus in complex regional pain syndrome

    PubMed Central

    Zhou, Guangyu; Hotta, Jaakko; Lehtinen, Maria K.; Forss, Nina; Hari, Riitta

    2015-01-01

    The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms. PMID:26388497

  9. Transplantation of choroid plexus epithelial cells into contusion-injured spinal cord of rats

    PubMed Central

    Kanekiyo, Kenji; Nakano, Norihiko; Noda, Toru; Yamada, Yoshihiro; Suzuki, Yoshihisa; Ohta, Masayoshi; Yokota, Atsushi; Fukushima, Masanori; Ide, Chizuka

    2016-01-01

    Purpose: The effect of the transplantation of choroid plexus epithelial cells (CPECs) on locomotor improvement and tissue repair including axonal extension in spinal cord lesions was examined in rats with spinal cord injury (SCI). Methods: CPECs were cultured from the choroid plexus of green fluorescent protein (GFP)-transgenic rats, and transplanted directly into the contusion-injured spinal cord lesions of rats of the same strain. Locomotor behaviors were evaluated based on BBB scores every week after transplantation until 4 weeks after transplantation. Histological and immunohistochemical examinations were performed at 2 days, and every week until 5 weeks after transplantation. Results: Locomotor behaviors evaluated by the BBB score were significantly improved in cell-transplanted rats. Numerous axons grew, with occasional interactions with CPECs, through the astrocyte-devoid areas. These axons exhibited structural characteristics of peripheral nerves. GAP-43-positive axons were found at the border of the lesion 2 days after transplantation. Cavity formation was more reduced in cell-transplanted than control spinal cords. CPECs were found within the spinal cord lesion, and sometimes in association with astrocytes at the border of the lesion until 2 weeks after transplantation. Conclusion: The transplantation of CPECs enhanced locomotor improvement and tissue recovery, including axonal regeneration, in rats with SCI. PMID:26923614

  10. Positron emission mammography (PEM): Effect of activity concentration, object size, and object contrast on phantom lesion detection

    SciTech Connect

    MacDonald, Lawrence R.; Wang, Carolyn L.; Eissa, Marna; Haseley, David; Kelly, Mary M.; Liu, Franklin; Parikh, Jay R.; Beatty, J. David; Rogers, James V.

    2012-10-15

    Purpose: To characterize the relationship between lesion detection sensitivity and injected activity as a function of lesion size and contrast on the PEM (positron emission mammography) Flex Solo II scanner using phantom experiments. Methods: Phantom lesions (spheres 4, 8, 12, 16, and 20 mm diameter) were randomly located in uniform background. Sphere activity concentrations were 3 to 21 times the background activity concentration (BGc). BGc was a surrogate for injected activity; BGc ranged from 0.44-4.1 kBq/mL, corresponding to 46-400 MBq injections. Seven radiologists read 108 images containing zero, one, or two spheres. Readers used a 5-point confidence scale to score the presence of spheres. Results: Sensitivity was 100% for lesions {>=}12 mm under all conditions except for one 12 mm sphere with the lowest contrast and lowest BGc (60% sensitivity). Sensitivity was 100% for 8 mm spheres when either contrast or BGc was high, and 100% for 4 mm spheres only when both contrast and BGc were highest. Sphere contrast recovery coefficients (CRC) were 49%, 34%, 26%, 14%, and 2.8% for the largest to smallest spheres. Cumulative specificity was 98%. Conclusions: Phantom lesion detection sensitivity depends more on sphere size and contrast than on BGc. Detection sensitivity remained {>=}90% for injected activities as low as 100 MBq, for lesions {>=}8 mm. Low CRC in 4 mm objects results in moderate detection sensitivity even for 400 MBq injected activity, making it impractical to optimize injected activity for such lesions. Low CRC indicates that when lesions <8 mm are observed on PEM images they are highly tracer avid with greater potential of clinical significance. High specificity (98%) suggests that image statistical noise does not lead to false positive findings. These results apply to the 85 mm thick object used to obtain them; lesion detectability should be better (worse) for thinner (thicker) objects based on the reduced (increased) influence of photon attenuation.

  11. The COX-2-Selective Antagonist (NS-398) Inhibits Choroidal Neovascularization and Subretinal Fibrosis

    PubMed Central

    Zhang, Ruoshuang; Liu, Zheli; Zhang, Han; Zhang, Yi; Lin, Dong

    2016-01-01

    Choroidal neovascularization (CNV) is an important pathologic component of neovascular age-related macular degeneration (AMD), and CNV lesions later develop into fibrous scars, which contribute to the loss of central vision. Nowadays, the precise molecular and cellular mechanisms underlying CNV and subretinal fibrosis have yet to be fully elucidated. Cyclooxygenase-2 (COX-2) has previously been implicated in angiogenesis and fibrosis. However, the role of COX-2 in the pathogenesis of CNV and subretinal fibrosis is poorly understood. The present study reveals several important findings concerning the relationship of COX-2 signaling with CNV and subretinal fibrosis. Experimental CNV lesions were attenuated by the administration of NS-398, a COX-2-selective antagonist. NS-398-induced CNV suppression was found to be mediated by the attenuation of macrophage infiltration and down-regulation of VEGF in the retinal pigment epithelium–choroid complex. Additionally, NS-398 attenuated subretinal fibrosis, in an experimental model of subretinal scarring observed in neovascular AMD, by down-regulation of TGF-β2 in the retinal pigment epithelium–choroid complex. Moreover, we cultured mouse RPE cells and found that NS-398 decreased the secretion of VEGF and TGF-β2 in mouse RPE cells. The results of the present study provide new findings regarding the molecular basis of CNV and subretinal fibrosis, and provide a proof-of-concept approach for the efficacy of COX-2 inhibition in treating subretinal fibrosis. PMID:26760305

  12. Pulmonary Adenocarcinoma Metastatic to the Choroid Diagnosed by Biopsy of an Extrascleral Nodule

    PubMed Central

    Jakobiec, Frederick A.; Ramsey, David J.; Stagner, Anna M.; Wu, David M.; Yoon, Michael K.

    2015-01-01

    Purpose/Background To report a patient with orbital extension of a choroidal metastasis produced by a pulmonary adenocarcinoma which was diagnosed by biopsy of the extrascleral nodule. Methods Clinical history and imaging studies (including fundus photography, autofluorescence, fluorescein angiography, B-scan, and orbital MRI) were reviewed along with histopathologic and immunohistochemical studies. Results A 60-year-old woman presented with decreased vision in the right eye. Fundus examination revealed a leopard-spotted choroidal lesion and associated serous retinal detachment. Imaging disclosed an enhancing orbital lesion abutting the sclera near the choroidal mass, which had spread outside of the eye. Histopathology revealed lumen-forming cells elaborating mucin. The cells were immunohistochemically positive for epithelial membrane antigen, thyroid transcription factor 1, and cytokeratin 7 and negative for cytokeratin 20. This was consistent with a pulmonary adenocarcinoma. Widespread metastases were subsequently found. Conclusions This is the first detailed case report of a successful biopsy of the orbital extension of an essentially posterior intraocular tumor. Such a maneuver permits a much more generous tissue sample than a needle biopsy. In the current case, a large tissue sample provided the basis for complete immunohistochemical evaluation, leading to the diagnosis of an intraocular metastatic mucin-producing adenocarcinoma of lung origin. PMID:27171574

  13. The Choroidal Eye Oximeter - An instrument for measuring oxygen saturation of choroidal blood in vivo

    NASA Technical Reports Server (NTRS)

    Laing, R. A.; Danisch, L. A.; Young, L. R.

    1975-01-01

    The Choroidal Eye Oximeter is an electro-optical instrument that noninvasively measures the oxygen saturation of choroidal blood in the back of the human eye by a spectrophotometric method. Since choroidal blood is characteristic of blood which is supplied to the brain, the Choroidal Eye Oximeter can be used to monitor the amount of oxygen which is supplied to the brain under varying external conditions. The instrument consists of two basic systems: the optical system and the electronic system. The optical system produces a suitable bi-chromatic beam of light, reflects this beam from the fundus of the subject's eye, and onto a low-noise photodetector. The electronic system amplifies the weak composite signal from the photodetector, computes the average oxygen saturation from the area of the fundus that was sampled, and displays the value of the computed oxygen saturation on a panel meter.

  14. CHOROIDAL IMAGING USING SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    Regatieri, Caio V.; Branchini, Lauren; Fujimoto, James G.; Duker, Jay S.

    2012-01-01

    Background A structurally and functionally normal choroidal vasculature is essential for retinal function. Therefore, a precise clinical understanding of choroidal morphology should be important for understanding many retinal and choroidal diseases. Methods PUBMED (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed) was used for most of the literature search for this article. The criterion for inclusion of an article in the references for this review was that it included materials about both the clinical and the basic properties of choroidal imaging using spectral-domain optical coherence tomography. Results Recent reports show successful examination and accurate measurement of choroidal thickness in normal and pathologic states using spectral-domain optical coherence tomography systems. This review focuses on the principles of the new technology that make choroidal imaging using optical coherence tomography possible and on the changes that subsequently have been documented to occur in the choroid in various diseases. Additionally, it outlines future directions in choroidal imaging. Conclusion Optical coherence tomography is now proven to be an effective noninvasive tool to evaluate the choroid and to detect choroidal changes in pathologic states. Additionally, choroidal evaluation using optical coherence tomography can be used as a parameter for diagnosis and follow-up. PMID:22487582

  15. Chronologic versus Biologic Aging of the Human Choroid

    PubMed Central

    May, Christian Albrecht

    2013-01-01

    Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch's membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease. PMID:24453840

  16. The effect of retrosplenial cortex lesions in rats on incidental and active spatial learning

    PubMed Central

    Nelson, A. J. D.; Hindley, E. L.; Pearce, J. M.; Vann, S. D.; Aggleton, J. P.

    2015-01-01

    The study examined the importance of the retrosplenial cortex for the incidental learning of the spatial arrangement of distinctive features within a scene. In a modified Morris water-maze, rats spontaneously learnt the location of an escape platform prior to swimming to that location. For this, rats were repeatedly placed on a submerged platform in one corner of either a rectangular (Experiment 1) or square (Experiments 2, 3) pool with walls of different appearance. The rats were then released in the center of the pool for their first test trial. In Experiment 1, the correct corner and its diagonally opposite partner (also correct) were specified by the geometric properties of the pool. Rats with retrosplenial lesions took longer to first reach a correct corner, subsequently showing an attenuated preference for the correct corners. A reduced preference for the correct corner was also found in Experiment 2, when platform location was determined by the juxtaposition of highly salient visual cues (black vs. white walls). In Experiment 3, less salient visual cues (striped vs. white walls) led to a robust lesion impairment, as the retrosplenial lesioned rats showed no preference for the correct corner. When subsequently trained actively to swim to the correct corner over successive trials, retrosplenial lesions spared performance on all three discriminations. The findings not only reveal the importance of the retrosplenial cortex for processing various classes of visuospatial information but also highlight a broader role in the incidental learning of the features of a spatial array, consistent with the translation of scene information. PMID:25705182

  17. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  18. Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion.

    PubMed

    Mine, S; Iwasa, H; Nakajima, Y; Yamaura, A

    2000-02-01

    Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background. PMID:15558875

  19. Regulation of Toll-like receptors in the choroid plexus in the immature brain after systemic inflammatory stimuli.

    PubMed

    Stridh, Linnea; Ek, C Joakim; Wang, Xiaoyang; Nilsson, Holger; Mallard, Carina

    2013-04-01

    The choroid plexus is the site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB) and has also been considered as a possible route for peripheral immune signals and cells to transfer to the central nervous system. Infection/inflammation stimulates innate and subsequent adaptive immune responses via Toll-like receptors (TLRs). In this study, we have investigated the mRNA expression of TLRs, cytokines, and tight junction proteins in the choroid plexus in the immature brain after systemic inflammation, as well as accumulation of immune cells into the CSF. Specific ligands for TLR-1/2, TLR-3, and TLR-4 were administered to postnatal day 8 mice and mRNA expression for the targeted genes was examined in the choroid plexus. We found that mRNA for all four TLRs was detected in the choroid plexus under control conditions. Following immune stimulation, expression of all the TLRs was upregulated by their respective ligands, except for TLR-4 mRNA, which was downregulated by Pam3CSK4 (PAM; a TLR-1/2 ligand). In addition, we investigated BCSFB regulation after TLR stimulation and found that TLR-1/2 and TLR-4 activation was associated with changes in mRNA expression of the tight junction protein occludin in the choroid plexus. PAM induced choroid plexus transcription of TNF-α and resulted in the most dramatic increase in numbers of white blood cells in the CSF. The data suggest a possible mechanism whereby systemic inflammation stimulates TLRs in the choroid plexus, which may lead to disturbances in choroid plexus barrier function, as well as infiltration of immune cells through the plexus. PMID:23741282

  20. Unilateral Glaucoma Associated with Conjunctival Angioma and Choroidal Thickening without Facial Angioma.

    PubMed

    Saeedi, Osamah J; Chang, Luke Y; Arora, Karun S; Jampel, Henry D; Quigley, Harry A

    2016-01-01

    We report a case of a suspected Sturge-Weber syndrome variant diagnosed at the age of 58 with the help of enhanced depth imaging spectral-domain ocular coherence tomography (EDI-SDOCT). A 58-year-old female with unilateral glaucoma was suspected to have choroidal vascular lesion, conjunctival angioma, and no facial port-wine stain who presented to the clinic with bleb dysesthesia many years after trabeculectomy. EDI-SDOCT was performed and revealed markedly increased choroidal thickness in the affected eye. EDI-SDOCT may be helpful in diagnosing Sturge-Weber variants without facial involvement and may aid in the investigation of the pathogenesis of this disease. PMID:27555719

  1. Preoperative radiotherapy in the management of posterior fossa choroid plexus papillomas.

    PubMed

    Carrea, R; Polak, M

    1977-01-01

    Although primary radical removal is the procedure of choice in the treatment of choroid plexus papillomas, the age of the child, the size and/or location of the tumor and an above average surgical risk can make advisable the use of a first stage shunt operation, with section of the tentorium if there are signs of upwards tentorial herniation. The present two observations clearly demonstrate that radiotherapy shrinks the vascular stroma of these tumors, thus reducing its size and vascularity making possible the postponement of radical surgery and greatly simplifying the final radical removal of the lesion. Preoperative radiotherapy as well as shunt operations and tentorial section can be considered as first stage procedures for the surgical management of choroid plexus neoplasms in certain cases. PMID:844343

  2. Unilateral Glaucoma Associated with Conjunctival Angioma and Choroidal Thickening without Facial Angioma

    PubMed Central

    Saeedi, Osamah J.; Chang, Luke Y.; Arora, Karun S.; Jampel, Henry D.; Quigley, Harry A.

    2016-01-01

    We report a case of a suspected Sturge–Weber syndrome variant diagnosed at the age of 58 with the help of enhanced depth imaging spectral-domain ocular coherence tomography (EDI-SDOCT). A 58-year-old female with unilateral glaucoma was suspected to have choroidal vascular lesion, conjunctival angioma, and no facial port-wine stain who presented to the clinic with bleb dysesthesia many years after trabeculectomy. EDI-SDOCT was performed and revealed markedly increased choroidal thickness in the affected eye. EDI-SDOCT may be helpful in diagnosing Sturge–Weber variants without facial involvement and may aid in the investigation of the pathogenesis of this disease. PMID:27555719

  3. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  4. Microwave plaque thermoradiotherapy for choroidal melanoma.

    PubMed Central

    Finger, P. T.

    1992-01-01

    Microwave thermoradiotherapy was used as a primary treatment for 44 patients with choroidal melanoma. An episcleral dish-shaped microwave antenna was placed beneath the tumour at the time of plaque brachytherapy. While temperatures were measured at the sclera, the tumour's apex was targeted to receive a minimum of 42 degrees C for 45 minutes. In addition, the patients received full or reduced doses of plaque radiotherapy. No patients have been lost to follow-up. Two eyes have been enucleated: one for rubeotic glaucoma, and one for uveitic glaucoma. Though six patients have died, only one death was due to metastatic choroidal melanoma (39 months after treatment). Clinical observations suggest that the addition of microwave heating to plaque radiation therapy of choroidal melanoma has been well tolerated. There has been a 97.7% local control rate (with a mean follow-up of 22.2 months). We have reduced the minimum tumour radiation dose (apex dose) to levels used for thermoradiotherapy of cutaneous melanomas (50 Gy/5000 rad). Within the range of this follow-up period no adverse effects which might preclude the use of this microwave heat delivery system for treatment of choroidal melanoma have been noted. Images PMID:1622949

  5. OB protein binds specifically to the choroid plexus of mice and rats.

    PubMed Central

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-01-01

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8643634

  6. OB protein binds specifically to the choroid plexus of mice and rats.

    PubMed

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-05-28

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor. PMID:8643634

  7. Distribution, activation and tryptase/chymase phenotype of mast cells in the rheumatoid lesion.

    PubMed Central

    Tetlow, L C; Woolley, D E

    1995-01-01

    OBJECTIVE--To determine the distribution, activation, and tryptase/chymase phenotype of mast cells (MCs) in the rheumatoid lesion. METHODS--MC tryptase and chymase were studied by immunohistochemistry using monoclonal antibodies and examination by brightfield, interference, and fluorescent microscopy. Thirty four specimens of cartilage-pannus junction and 26 specimens of rheumatoid synovium, all derived from knee surgery, were examined. RESULTS--MCs were identified in all specimens examined, but their distribution and local concentrations varied, both within and between specimens. As a proportion of total synovial cells, there were more MCs in fibrous synovial tissues than in those with active inflammatory cell infiltrations; MCs usually showed a peripheral distribution around lymphocytic/mononuclear cell infiltrations. Most cartilage-pannus specimens demonstrated local concentrations of MCs at, or close to, sites of cartilage erosion, a significant proportion of which showed extracellular tryptase indicative of MC degranulation. MC degranulation was often associated with localised oedema and disruption of the stromal matrix. Two MC phenotypes were identified: one population contained tryptase alone (MCT) whilst another contained both tryptase and chymase (MCTC). The ratio MCT:MCTC approximated 8:1. CONCLUSIONS--This histological study demonstrated that local concentrations of MCs and their activation/degranulation are commonly observed in the rheumatoid lesion, and especially at sites of cartilage erosion. Such observations add weight to the concept that MCs contribute to the processes of inflammation, matrix degradation and tissue remodelling. Images PMID:7668897

  8. Weekly multimodal MRI follow-up of two multiple sclerosis active lesions presenting a transient decrease in ADC

    PubMed Central

    Hannoun, Salem; Roch, Jean-Amédée; Durand-Dubief, Francoise; Vukusic, Sandra; Sappey-Marinier, Dominique; Guttmann, Charles RG; Cotton, Francois

    2015-01-01

    Background and purpose Blood-brain barrier disruption during the earliest phases of lesion formation in multiple sclerosis (MS) patients is commonly ascribed to perivenular inflammatory activity and is usually accompanied by increased diffusivity. Reduced diffusivity has also been shown in active lesions, albeit less frequently. This study aimed to characterize the development and natural history of contrast-enhanced lesions by weekly following five relapsing remitting (RR) MS patients. Materials and methods Diffusion tensor imaging (DTI), perfusion imaging, FLAIR and contrast-enhanced 3D T1-weighted MR, were weekly performed on five untreated patients recently diagnosed with RR MS. Results All five patients showed significant increases of the apparent diffusion coefficient (ADC) in the lesions compared to the first time point. One of the five patients presented 98 active lesions on ADC maps among which 36 had a volume larger than 10 mm3. In two of these lesions, a 1 week transient decrease in ADC was detected at the time of the first gadolinium enhancement. Also, the perfusion analysis showed a concomitant increase in the relative cerebral blood volume. Conclusions The infrequency detection of such ADC decrease in a new lesion is probably due to its very short duration. This observation may be consistent with a hyper-acute inflammatory stage concomitant with an increased reactional perfusion. PMID:25642392

  9. Spectral embedding based active contour (SEAC): application to breast lesion segmentation on DCE-MRI

    NASA Astrophysics Data System (ADS)

    Agner, Shannon C.; Xu, Jun; Rosen, Mark; Karthigeyan, Sudha; Englander, Sarah; Madabhushi, Anant

    2011-03-01

    Spectral embedding (SE), a graph-based manifold learning method, has previously been shown to be useful in high dimensional data classification. In this work, we present a novel SE based active contour (SEAC) segmentation scheme and demonstrate its applications in lesion segmentation on breast dynamic contrast enhance magnetic resonance imaging (DCE-MRI). In this work, we employ SE on DCE-MRI on a per voxel basis to embed the high dimensional time series intensity vector into a reduced dimensional space, where the reduced embedding space is characterized by the principal eigenvectors. The orthogonal eigenvector-based data representation allows for computation of strong tensor gradients in the spectrally embedded space and also yields improved region statistics that serve as optimal stopping criteria for SEAC. We demonstrate both analytically and empirically that the tensor gradients in the spectrally embedded space are stronger than the corresponding gradients in the original grayscale intensity space. On a total of 50 breast DCE-MRI studies, SEAC yielded a mean absolute difference (MAD) of 3.2+/-2.1 pixels and mean Dice similarity coefficient (DSC) of 0.74+/-0.13 compared to manual ground truth segmentation. An active contour in conjunction with fuzzy c-means (FCM+AC), a commonly used segmentation method for breast DCE-MRI, produced a corresponding MAD of 7.2+/-7.4 pixels and mean DSC of 0.58+/-0.32. In conjunction with a set of 6 quantitative morphological features automatically extracted from the SEAC derived lesion boundary, a support vector machine (SVM) classifier yielded an area under the curve (AUC) of 0.73, for discriminating between 10 benign and 30 malignant lesions; the corresponding SVM classifier with the FCM+AC derived morphological features yielded an AUC of 0.65.

  10. A new background distribution-based active contour model for three-dimensional lesion segmentation in breast DCE-MRI

    SciTech Connect

    Liu, Hui; Liu, Yiping; Qiu, Tianshuang; Zhao, Zuowei; Zhang, Lina

    2014-08-15

    Purpose: To develop and evaluate a computerized semiautomatic segmentation method for accurate extraction of three-dimensional lesions from dynamic contrast-enhanced magnetic resonance images (DCE-MRIs) of the breast. Methods: The authors propose a new background distribution-based active contour model using level set (BDACMLS) to segment lesions in breast DCE-MRIs. The method starts with manual selection of a region of interest (ROI) that contains the entire lesion in a single slice where the lesion is enhanced. Then the lesion volume from the volume data of interest, which is captured automatically, is separated. The core idea of BDACMLS is a new signed pressure function which is based solely on the intensity distribution combined with pathophysiological basis. To compare the algorithm results, two experienced radiologists delineated all lesions jointly to obtain the ground truth. In addition, results generated by other different methods based on level set (LS) are also compared with the authors’ method. Finally, the performance of the proposed method is evaluated by several region-based metrics such as the overlap ratio. Results: Forty-two studies with 46 lesions that contain 29 benign and 17 malignant lesions are evaluated. The dataset includes various typical pathologies of the breast such as invasive ductal carcinoma, ductal carcinomain situ, scar carcinoma, phyllodes tumor, breast cysts, fibroadenoma, etc. The overlap ratio for BDACMLS with respect to manual segmentation is 79.55% ± 12.60% (mean ± s.d.). Conclusions: A new active contour model method has been developed and shown to successfully segment breast DCE-MRI three-dimensional lesions. The results from this model correspond more closely to manual segmentation, solve the weak-edge-passed problem, and improve the robustness in segmenting different lesions.

  11. In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

    PubMed

    Crespo-Garcia, Sergio; Reichhart, Nadine; Hernandez-Matas, Carlos; Zabulis, Xenophon; Kociok, Norbert; Brockmann, Claudia; Joussen, Antonia M; Strauss, Olaf

    2015-10-01

    Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach

  12. Lesions Arising in a Tattoo of an Active Duty US Marine Corps Woman.

    PubMed

    Winn, Aubrey E; Rivard, Shayna C; Green, Brian

    2016-01-01

    Tattoos are ubiquitous in modern society; however, they do not come without risk of medical complications. When complications arise in the military community, a particularly thorough differential diagnosis should be considered based on the increased exposures service members have during deployment and throughout their military career. We present a case of a 38-year-old active duty US Marine Corps woman with worsening skin lesions arising within a tattoo 6 weeks after acquiring the tattoo on her right chest. Given environmental exposures from a recent deployment to the Middle East, a wide differential was considered. Ultimately, a skin biopsy revealed early hypertrophic scar formation responsive to therapy with intralesional triamcinolone acetonide (Kenalog® [ILK]). However, given the Marine had recently deployed and is part of the active duty population, consideration of alternative, albeit rare, etiologies was imperative. PMID:27450611

  13. Macrophage polarization in experimental and clinical choroidal neovascularization

    PubMed Central

    Yang, Yu; Liu, Fang; Tang, Miao; Yuan, Miner; Hu, Andina; Zhan, Zongyi; Li, Zijing; Li, Jiaqing; Ding, Xiaoyan; Lu, Lin

    2016-01-01

    Macrophages play an important role in the development of age-related macular degeneration (AMD). In this study, the spatial and temporal changes and the polarization of macrophages in murine laser-induced choroidal neovascularization (CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main infiltrating inflammatory cells in CNV lesions, were evidenced by a significant increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related markers were dramatically upregulated in the early stage, while the M2-related markers were slightly upregulated in the middle stage and sustained until the late stage. The results of immunostaining showed a similar early-but-transient M1 pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition, a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the controls. Our results suggested that the dynamic patterns of M1 and M2 were different in both the experimental and clinical CNV. The M2 macrophages were predominant and may play a more important role in the development of CNV. PMID:27489096

  14. Transcriptomal changes and functional annotation of the developing non-human primate choroid plexus

    PubMed Central

    Ek, C. Joakim; Nathanielsz, Peter; Li, Cun; Mallard, Carina

    2015-01-01

    The choroid plexuses are small organs that protrude into each brain ventricle producing cerebrospinal fluid that constantly bathes the brain. These organs differentiate early in development just after neural closure at a stage when the brain is little vascularized. In recent years the plexus has been shown to have a much more active role in brain development than previously appreciated thereby it can influence both neurogenesis and neural migration by secreting factors into the CSF. However, much of choroid plexus developmental function is still unclear. Most previous studies on this organ have been undertaken in rodents but translation into humans is not straightforward since they have a different timing of brain maturation processes. We have collected choroid plexus from three fetal gestational ages of a non-human primate, the baboon, which has much closer brain development to humans. The transcriptome of the plexuses was determined by next generation sequencing and Ingenuity Pathway Analysis software was used to annotate functions and enrichment of pathways of changes in the transcriptome. The number of unique transcripts decreased with development and the majority of differentially expressed transcripts were down-regulated through development suggesting a more complex and active plexus earlier in fetal development. The functional annotation indicated changes across widespread biological functions in plexus development. In particular we find age-dependent regulation of genes associated with annotation categories: Gene Expression, Development of Cardiovascular System, Nervous System Development and Molecular Transport. Our observations support the idea that the choroid plexus has roles in shaping brain development. PMID:25814924

  15. Transcriptomal changes and functional annotation of the developing non-human primate choroid plexus.

    PubMed

    Ek, C Joakim; Nathanielsz, Peter; Li, Cun; Mallard, Carina

    2015-01-01

    The choroid plexuses are small organs that protrude into each brain ventricle producing cerebrospinal fluid that constantly bathes the brain. These organs differentiate early in development just after neural closure at a stage when the brain is little vascularized. In recent years the plexus has been shown to have a much more active role in brain development than previously appreciated thereby it can influence both neurogenesis and neural migration by secreting factors into the CSF. However, much of choroid plexus developmental function is still unclear. Most previous studies on this organ have been undertaken in rodents but translation into humans is not straightforward since they have a different timing of brain maturation processes. We have collected choroid plexus from three fetal gestational ages of a non-human primate, the baboon, which has much closer brain development to humans. The transcriptome of the plexuses was determined by next generation sequencing and Ingenuity Pathway Analysis software was used to annotate functions and enrichment of pathways of changes in the transcriptome. The number of unique transcripts decreased with development and the majority of differentially expressed transcripts were down-regulated through development suggesting a more complex and active plexus earlier in fetal development. The functional annotation indicated changes across widespread biological functions in plexus development. In particular we find age-dependent regulation of genes associated with annotation categories: Gene Expression, Development of Cardiovascular System, Nervous System Development and Molecular Transport. Our observations support the idea that the choroid plexus has roles in shaping brain development. PMID:25814924

  16. Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage

    PubMed Central

    Tan, Xue; Fujiu, Katsuhito; Manabe, Ichiro; Nishida, Junko; Yamagishi, Reiko; Terashima, Yuya; Matsushima, Kouji; Kaburaki, Toshikatsu; Nagai, Ryozo; Yanagi, Yasuo

    2016-01-01

    Purpose To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. Methods We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. Results In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4–/–or Rag2–/–mice and controls, whereas lesion size was significantly reduced in CCR2−/− mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular

  17. Actively bleeding Dieulafoy’s lesion of the small bowel identified by capsule endoscopy and treated by push enteroscopy

    PubMed Central

    Palma, Giovanni D De; Patrone, Francesco; Rega, Maria; Simeoli, Immacolata; Masone, Stefania; Persico, Giovanni

    2006-01-01

    Dieulafoy’s lesion is an unusual cause of recurrent GI bleeding. This report describes a case of actively bleeding Dieulafoy’s lesion of the small bowel in which the diagnosis was made by capsule endoscopy, followed by treatment with the use of push enteroscopy. The case illustrates that capsule endoscopy and enteroscopy are highly complementary in patients with small bowel diseases. PMID:16804987

  18. Reduced choice-related activity and correlated noise accompany perceptual deficits following unilateral vestibular lesion

    PubMed Central

    Liu, Sheng; Dickman, J. David; Newlands, Shawn D.; DeAngelis, Gregory C.; Angelaki, Dora E.

    2013-01-01

    Signals from the bilateral vestibular labyrinths work in tandem to generate robust estimates of our motion and orientation in the world. The relative contributions of each labyrinth to behavior, as well as how the brain recovers after unilateral peripheral damage, have been characterized for motor reflexes, but never for perceptual functions. Here we measure perceptual deficits in a heading discrimination task following surgical ablation of the neurosensory epithelium in one labyrinth. We found large increases in heading discrimination thresholds and large perceptual biases at 1 wk postlesion. Repeated testing thereafter improved heading perception, but vestibular discrimination thresholds remained elevated 3 mo postlesion. Electrophysiological recordings from the contralateral vestibular and cerebellar nuclei revealed elevated neuronal discrimination thresholds, elevated neurometric-to-psychometric threshold ratios, and reduced trial-by-trial correlations with perceptual decisions [“choice probabilities” (CPs)]. The relationship between CP and neuronal threshold was shallower, but not significantly altered, suggesting that smaller CPs in lesioned animals could be largely attributable to greater neuronal thresholds. Simultaneous recordings from pairs of neurons revealed that correlated noise among neurons was also reduced following the lesion. Simulations of a simple pooling model, which takes into account the observed changes in tuning slope and correlated noise, qualitatively accounts for the elevated psychophysical thresholds and neurometric-to-psychometric ratios, as well as the decreased CPs. Thus, cross-labyrinthine interactions appear to play important roles in enhancing neuronal and perceptual sensitivity, strengthening interneuronal correlations, and facilitating correlations between neural activity and perceptual decisions. PMID:24127575

  19. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  20. A case of giant nodular posterior scleritis mimicking choroidal malignancy

    PubMed Central

    Liu, Andrea T; Luk, Fiona O; Chan, Carmen K

    2015-01-01

    To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biospy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure. PMID:26862098

  1. Choroid Melanoma Metastasis to Spine: A Rare Case Report.

    PubMed

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  2. ACTIVATION OF PPAR GAMMA RECEPTORS REDUCES LEVODOPA-INDUCED DYSKINESIAS IN 6-OHDA-LESIONED RATS

    PubMed Central

    Martinez, A. A.; Morgese, M. G.; Pisanu, A.; Macheda, T.; Paquette, M. A.; Seillier, A.; Cassano, T.; Carta, A.R.; Giuffrida, A.

    2014-01-01

    Long-term administration of L-3,4-dihydroxyphenylalanine (levodopa), the mainstay treatment for Parkinson’s disease (PD), is accompanied by fluctuations in its duration of action and motor complications (dyskinesia) that dramatically affect the quality of life of patients. Levodopa-induced dyskinesias (LID) can be modeled in rats with unilateral 6-OHDA lesions via chronic administration of levodopa, which causes increasingly severe axial, limb and oro-facial abnormal involuntary movements (AIMs) over time. In previous studies, we showed that direct activation of CB1 cannabinoid receptors alleviated rat AIMs. Interestingly, elevation of the endocannabinoid anandamide by URB597 (URB), an inhibitor of endocannabinoid catabolism, produced an anti-dyskinetic response that was only partially mediated via CB1 receptors and required the concomitant blockade of transient receptor potential vanilloid type-1 (TRPV1) channels by capsazepine (CPZ) [1]. In this study, we showed that stimulation of peroxisome proliferator-activated receptors (PPAR), a family of transcription factors activated by anandamide, contributes to the anti-dyskinetic effects of URB+CPZ, and that direct activation of the PPARγ subtype by rosiglitazone (RGZ) alleviates levodopa-induced AIMs in 6-OHDA rats. AIM reduction was associated with an attenuation of levodopa-induced increase of dynorphin, zif-268 and of ERK phosphorylation in the denervated striatum. RGZ treatment did not decrease striatal levodopa and dopamine bioavailability, nor did it affect levodopa antiparkinsonian activity. Collectively, these data indicate that PPARγ may represent a new pharmacological target for the treatment of LID. PMID:25486547

  3. Structural changes of the choroid in sarcoid- and tuberculosis-related granulomatous uveitis

    PubMed Central

    Mehta, H; Sim, D A; Keane, P A; Zarranz-Ventura, J; Gallagher, K; Egan, C A; Westcott, M; Lee, R W J; Tufail, A; Pavesio, C E

    2015-01-01

    Aim The aim of this study is to characterise the choroidal features of patients diagnosed with sarcoid- and tuberculosis (TB)-associated granulomatous uveitis using spectral domain optical coherence tomography (OCT). Methods Twenty-seven patients (27 eyes) diagnosed with sarcoid- (13 eyes) and TB (14 eyes)-related uveitis were included in this retrospective, cross-sectional study. Over a six-month period, patients diagnosed with sarcoid and TB granulomatous uveitis were scanned using enhanced depth imaging OCT. Clinical and demographical characteristics were recorded, including the method of diagnosis, disease activity, site of inflammation (anterior or posterior), treatments, and visual acuity (VA). Manual segmentation of the choroidal layers was performed using custom image analysis software. Results The main outcome measure was OCT-derived thickness measurements of the choroid and choroidal sublayers (Haller's large vessel and Sattler's medium vessel layers) at the macula region. The ratio of Haller's large vessel to Sattler's medium vessel layer was significantly different at the total macula circle in eyes diagnosed with TB uveitis (1.47 (=140.71/95.72 μm)) compared with sarcoid uveitis (1.07 (=137.70/128.69 μm)) (P=0.001). A thinner choroid was observed in eyes with a VA ≥0.3 LogMAR (Snellen 6/12; 198.1 μm (interquartile range (IQR)=147.0–253.4 μm) compared with those with VA <0.3 LogMAR (292.4 μm (IQR=240.1–347.6 μm)) at the total macula circle (P=0.004). At the foveal central subfield, the median choroidal thickness was 336.8 μm (IQR=272.3–375.4 μm) in active compared with 239.3 μm (IQR=195.3–330.9 μm) in quiescent disease (P=0.04). Conclusion A disproportionately enlarged Sattler's layer may indicate a diagnosis of sarcoid-related uveitis, and choroidal thickening may be a feature of active granulomatous uveitis. PMID:26021867

  4. Effectiveness of sealing active proximal caries lesions with an adhesive system: 1-year clinical evaluation.

    PubMed

    Abuchaim, Clarisse; Rotta, Marina; Grande, Rosa Helena Miranda; Loguercio, Alessandro Dourado; Reis, Alessandra

    2010-01-01

    The objective of this study was to evaluate the effectiveness of a therapeutic sealant to arrest non-cavitated proximal carious lesion progression. The study population comprised 44 adolescents who had bitewing radiographs taken for caries diagnosis. Non-cavitated lesions extending up to half of dentin thickness were included in the sample. In the experimental group (n = 33), the proximal caries-lesion surfaces were sealed with an adhesive (OptiBond Solo, Kerr) after tooth separation. The control group (n = 11) received no treatment, except for oral hygiene instructions including use of dental floss. Follow-up radiographs were taken after one year and were analyzed in comparison with baseline radiographs. In a blind study setting, visual readings were performed by two examiners, blinded to whether the examined radiograph was baseline or follow-up, and whether it concerned a test or control lesion. The efficacy of sealing treatment was evaluated by the McNemar test (0.05). About 22% of the sealed lesions showed reduction, 61% showed no change and 16% showed progression. For the control lesions, the corresponding values were 27%, 36% and 36% respectively. The number of lesions that showed reduction and no changes were merged and therefore 83.3% of the sealed lesions and 63.6% of the control lesions were considered clinically successful. No statistical significance was detected (p > 0.05). In the course of 1 year, sealing proximal caries lesions was not shown to be superior to lesion monitoring. PMID:20877976

  5. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  6. Pachychoroid neovasculopathy in extramacular choroidal neovascularization

    PubMed Central

    Gupta, Mrinali Patel; Rusu, Irene; Seidman, Carly; Orlin, Anton; D’Amico, Donald J; Kiss, Szilard

    2016-01-01

    Purpose To review a series of extramacular choroidal neovascular membranes (CNVMs) in the context of their choroidal features, as determined by optical coherence tomography (OCT). Methods Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA), and indocyanine angio-graphy (ICG). Results Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7%) exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM. Conclusion Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. PMID:27471372

  7. Notch3 Activation Promotes Invasive Glioma Formation in a Tissue Site-Specific Manner

    PubMed Central

    Pierfelice, Tarran J.; Schreck, Karisa C.; Dang, Louis; Asnaghi, Laura; Gaiano, Nicholas; Eberhart, Charles G.

    2010-01-01

    While Notch signaling has been widely implicated in neoplastic growth, direct evidence for in vivo initiation of neoplasia by the pathway in murine models has been limited to tumors of lymphoid, breast, and choroid plexus cells. To examine tumorigenic potential in the eye and brain, we injected retroviruses encoding activated forms of Notch1, Notch2, or Notch3 into embryonic mice. Interestingly, the majority of animals infected with active Notch3 developed proliferative lesions comprised of pigmented ocular choroid cells, retinal and optic nerve glia, and lens epithelium. Notch3-induced lesions in the choroid, retina, and optic nerve were capable of invading adjacent tissues, suggesting that they were malignant tumors. While Notch3 activation induced choroidal tumors in up to 67% of eyes, Notch1 or Notch2 activation never resulted in such tumors. Active forms of Notch1 and Notch2 did generate a few small proliferative glial nodules in the retina and optic nerve, while Notch3 was ten-fold more efficient at generating growths, many of which were large invasive gliomas. Expression of active Notch1/Notch3 chimeric receptors implicated the RAM (RBPjk-association molecule) and transactivation domains (TAD) of Notch3 in generating choroidal and glial tumors, respectively. In contrast to our findings in the optic nerve and retina, introduction of active Notch receptors, including Notch3, into the brain never caused glial tumors. Our results highlight the differential ability of Notch receptor paralogs to initiate malignant tumor formation, and suggest that glial precursors of the optic nerve, but not the brain, are susceptible to transformation by Notch3. PMID:21245095

  8. Is There Any Role for the Choroid in Glaucoma?

    PubMed

    Goharian, Iman; Sehi, Mitra

    2016-05-01

    The choroid is part of the uveal tract and is a heavily vascularized bed that also contains connective tissue and melanin pigment. Given the role of the choroidal vasculature in the blood supply of the anterior laminar and prelaminar regions of the optic nerve head, the peripapillary choroid might be a relevant target for investigation in patients with glaucoma. The purpose of this paper is to critically review the current understanding of potential role of the choroid in the pathogenesis of glaucomatous damage. PMID:25265007

  9. Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment

    PubMed Central

    Yin, Houfa; Fang, Xiaoyun; Ma, Jian; Chen, Min; Yang, Yabo; Guo, Shenchao; Chen, Zhiqing; Su, Zhaoan; Feng, Lei; Ye, Panpan; Wu, Fang; Yin, Jinfu

    2016-01-01

    Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV, and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF, and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF, and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL-2, IL-10, basic FGF, and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV. PMID:27558944

  10. Retinal and Choroidal Folds in Papilledema

    PubMed Central

    Sibony, Patrick A.; Kupersmith, Mark J.; Feldon, Steven E.; Wang, Jui-Kai; Garvin, Mona

    2015-01-01

    Purpose To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). Methods Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. Results We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. Conclusions Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.) PMID:26335066

  11. The choroid plexus-cerebrospinal fluid interface in Alzheimer's disease: more than just a barrier

    PubMed Central

    Balusu, Sriram; Brkic, Marjana; Libert, Claude; Vandenbroucke, Roosmarijn E.

    2016-01-01

    The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial (CPE) cells surrounding fenestrated capillaries. These CPE cells not only form an anatomical barrier, called the blood-cerebrospinal fluid barrier (BCSFB), but also present an active interface between blood and cerebrospinal fluid (CSF). CPE cells perform indispensable functions for the development, maintenance and functioning of the brain. Indeed, the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules, such as nutrients, neurotrophins, and growth factors, as well as by clearing toxic and undesirable molecules from CSF. The choroid plexus also acts as a selective entry gate for leukocytes into the brain. Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer's disease. In this review, we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer's disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy. PMID:27212900

  12. Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions

    PubMed Central

    Popescu, Bogdan F.G.; Guo, Yong; Jentoft, Mark E.; Parisi, Joseph E.; Lennon, Vanda A.; Pittock, Sean J.; Weinshenker, Brian G.; Wingerchuk, Dean M.; Giannini, Caterina; Metz, Imke; Brück, Wolfgang; Shuster, Elizabeth A.; Carter, Jonathan; Boyd, Clara D.; Clardy, Stacey Lynn; Cohen, Bruce A.

    2015-01-01

    Objective: To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4–immunoglobulin G (IgG) serologic testing. Methods: This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury. Results: AQP4 immunoreactivity was lost in 18 biopsies and increased in 2. Immunopathologic features of the AQP4 loss cohort were myelin vacuolation (18), dystrophic astrocytes and granulocytes (17), vascular hyalinization (16), macrophages containing glial fibrillary acid protein (GFAP)–positive debris (14), and Creutzfeldt-Peters cells (0). All 14 cases with available serum tested positive for AQP4-IgG after biopsy. Diagnosis at last follow-up was NMO/NMOSD (15) and longitudinally extensive transverse myelitis (1 each relapsing and single). Immunopathologic features of the AQP4 increased cohort were macrophages containing GFAP-positive debris and granulocytes (2), myelin vacuolation (1), dystrophic astrocytes (1), Creutzfeldt-Peters cells (1), and vascular hyalinization (1). Diagnosis at last follow-up was multiple sclerosis (MS) and both tested AQP4-IgG seronegative after biopsy. Conclusions: AQP4 immunohistochemistry with subsequent AQP4-IgG testing has diagnostic utility in identifying cases of NMO/NMOSD. This study highlights the importance of considering NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions. AQP4-IgG testing may avert biopsy and avoid ineffective therapies if these patients are erroneously treated for MS. PMID:25503621

  13. Retinal oxygenation via the choroidal circulation.

    PubMed Central

    Landers, M B

    1978-01-01

    The possibility of supplying normal amounts of oxygen to the inner layers of the retina by diffusion from the choroid in the presence of retinal arterial obstruction was studied in cats and rhesus monkeys. While the animals were under general anesthesia, an oxygen electrode was placed in the vitreous cavity immediately adjacent to the retina, and a retinal artery blocker probe was used to occlude various segments of the retina blood supply. The inspired oxygen concentration was alternated between 20% and 100%. The choroidal circulation was intermittently occluded by elevating the intraocular pressure. In all animals it was possible to return the oxygen tension of the innermost retina to normal concentrations or above while the retinal arterial circulation alone was occluded, by having the animal breathe 100% oxygen at one atmosphere pressure. This could not be done when the intraocular pressure was elevated to 85 mm Hg, occluding the choroidal as well as the retinal circulation. The electroretinogram and the visually evoked response were recorded in cats while the retinal circulation was occluded and the inspired oxygen concentration changed from 20% to 100% at one atmosphere pressure. The electroretinogram and the visually evoked response were extinguished by occluding the retinal circulation while the animal was breathing 20% oxygen, and these responses were returned to normal by changing to a 100% inspired oxygen concentration. Images FIGURE 6 PMID:112752

  14. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    SciTech Connect

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed; Corriveau, Christine; Edelstein, Chaim; Deschenes, Jean; Ruo, Russel; Patrocinio, Horacio; Cury, Fabio L.B.; DeBlois, Francois; Shenouda, George

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

  15. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy.

    PubMed

    Mohla, Aditi; Khan, Kamron; Kasilian, Melissa; Michaelides, Michel

    2016-01-01

    We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography. PMID:27587748

  16. Comparable reduction in Zif268 levels and cytochrome oxidase activity in the retrosplenial cortex following mammillothalamic tract lesions.

    PubMed

    Frizzati, Aura; Milczarek, Michal M; Sengpiel, Frank; Thomas, Kerrie L; Dillingham, Christopher M; Vann, Seralynne D

    2016-08-25

    Damage to the mammillothalamic tract (MTT) produces memory impairments in both humans and rats, yet it is still not clear why this diencephalic pathway is vital for memory. One suggestion is that it is an important route for midbrain inputs to reach a wider cortical and subcortical network that supports memory. Consistent with this idea, MTT lesions produce widespread hypoactivity in distal brain regions as measured by the immediate-early gene, c-fos. To determine whether these findings were selective to c-fos or reflected more general changes in neuronal function, we assessed the effects of MTT lesions on the expression of the immediate-early gene protein, Zif268 and the metabolic marker, cytochrome oxidase, in the retrosplenial cortex and hippocampus. The lesions decreased levels of both activity markers in the superficial and deep layers of the retrosplenial cortex in both its granular and dysgranular subregions. In contrast, no significant changes were observed in the hippocampus, despite the MTT-lesioned animals showing marked impairments on T-maze alternation. These findings are consistent with MTT lesions providing important, indirect inputs for normal retrosplenial cortex functioning. These distal functional changes may contribute to the memory impairments observed after MTT lesions. PMID:27233617

  17. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

  18. Effects of vasoactive stimuli on blood flow to choroid plexus

    SciTech Connect

    Faraci, F.M.; Mayhan, W.G.; Williams, J.K.; Heistad, D.D. )

    1988-02-01

    The goal of this study was to examine effects of vasoactive stimuli on blood flow to choroid plexus. The authors 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-{mu}m microspheres were similar, which suggest that shunting of 15-{mu}m microspheres was minimal. Blood flow to choroid plexus under control conditions was 287 {plus minus} 26 (means {plus minus} SE) ml {center dot} min{sup {minus}1} {center dot} 100 g{sup {minus}1} in dogs and 385 {plus minus} 73 ml {center dot} min{sup {minus}1} 100 g{sup {minus}1} in rabbits. Consecutive measurements under control conditions indicated that values for blood flow are reproducible. Adenosine did not alter blood flow to cerebrum but increased blood flow to choroid plexus two- to threefold in dogs and rabbits. Norepinephrine and phenylephrine did not affect blood flow to choroid plexus and cerebrum but decreased blood flow to choroid plexus by {approx} 50%. The authors 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.

  19. Noninvasive control of dental caries in children with active initial lesions. A randomized clinical trial.

    PubMed

    Hausen, H; Seppa, L; Poutanen, R; Niinimaa, A; Lahti, S; Kärkkäinen, S; Pietilä, I

    2007-01-01

    The aim of this study was to investigate whether DMFS increment can be decreased among children with active initial caries by oral hygiene and dietary counseling and by using noninvasive preventive measures. Except for mentally disabled and handicapped children attending special schools, all 11- to 12-year-olds in Pori, Finland, with at least one active initial caries lesion were invited to participate in the study and were then randomized into two groups. Children in the experimental group (n = 250) were offered an individually designed patient-centered preventive program aimed at identifying and eliminating factors that had led to the presence of active caries. The program included counseling sessions with emphasis on enhancing use of the children's own resources in everyday life. Toothbrushes, fluoride toothpaste and fluoride and xylitol lozenges were distributed to the children. They also received applications of fluoride/chlorhexidine varnish. The children in the control group (n = 247) received basic prevention offered as standard in the public dental clinics in Pori. For both groups, the average follow-up period was 3.4 years. A community level program of oral health promotion was run in Pori throughout this period. Mean DMFS increments for the experimental and control groups were 2.56 (95% CI 2.07, 3.05) and 4.60 (3.99, 5.21), respectively (p < 0.0001): prevented fraction 44.3% (30.2%, 56.4%). The results show that by using a regimen that includes multiple measures for preventing dental decay, caries increment can be significantly reduced among caries-active children living in an area where the overall level of caries experience is low. PMID:17713339

  20. Diagnosis and Follow-Up of Nonexudative Choroidal Neovascularization With Multiple Optical Coherence Tomography Angiography Devices: A Case Report.

    PubMed

    Lane, Mark; Ferrara, Daniela; Louzada, Ricardo Noguera; Fujimoto, James G; Seddon, Johanna M

    2016-08-01

    Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:778-781.]. PMID:27548457

  1. Application of Intravitreal Bevacizumab for Circumscribed Choroidal Hemangioma

    PubMed Central

    Sagong, Min; Lee, Junyeop

    2009-01-01

    We report 3 cases of circumscribed choroidal hemangioma (CCH) effectively managed with intravitreal bevacizumab. One patient (case 1) who had recurrent CCH (1.6 mm in thickness) with prior laser photocoagulation was treated with intravitreal bevacizumab alone. Two patients (case 2 and 3) who had CCH (2.4 mm and 2.2 mm in thickness, respectively) with recent visual impairment were treated with bevacizumab followed by photodynamic therapy (PDT). Ophthalmic evaluations included visual acuity, ophthalmoscopic examination, fluorescein angiography, ultrasonography, and optical coherence tomography. Patients were followed up for 6-9 months. After therapy, all patients showed improved visual acuity due to complete resorption of subretinal fluid and macular edema. Ultrasonography demonstrated a reduction of the thickness of CCH in case 1 and complete regression of the lesions in case 2 and 3. No patient showed tumor recurrence. Intravitreal bevacizumab, alone or in combination therapy with PDT, may be a useful alternative for the treatment of symptomatic CCH with subretinal fluid. PMID:19568366

  2. Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of CXCR4 and CXCR7 Expression in Choroid Endothelial Cell

    PubMed Central

    Feng, Yi-fan; Guo, Hua; Yuan, Fei; Shen, Min-qian

    2015-01-01

    Stromal cell-derived factor-1 (SDF-1) has been confirmed to participate in the formation of choroidal neovascularization (CNV) via its two receptors: CXC chemokine receptors 4 (CXCR4) and CXCR7. Previous studies have indicated that the activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS) might elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological angiogenesis formation remains to be elucidated. The present study shows that LPS enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in choroid-retinal endothelial (RF/6A) cells. In addition, the transcriptional regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation of the extracellular signal-related kinase (ERK) 1/2 and activation of nuclear factor kappa B (NF-κB) signaling pathways, which were blocked by ERK- or NF-κB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4 and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat. SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in LPS-treated rat after a single intravitreal injection. Altogether, these results demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7 expression in endothelial cells, possibly providing a new perspective for the treatment of CNV-associated diseases. PMID:26288180

  3. Recurrent Annular Peripheral Choroidal Detachment after Trabeculectomy

    PubMed Central

    Liu, Shaohui; Sun, Lisa L.; Kavanaugh, A. Scott; Langford, Marlyn P.; Liang, Chanping

    2013-01-01

    We report a challenging case of recurrent flat anterior chamber without hypotony after trabeculectomy in a 54-year-old Black male with a remote history of steroid-treated polymyositis, cataract surgery, and uncontrolled open angle glaucoma. The patient presented with a flat chamber on postoperative day 11, but had a normal fundus exam and intraocular pressure (IOP). Flat chamber persisted despite treatment with cycloplegics, steroids, and a Healon injection into the anterior chamber. A transverse B-scan of the peripheral fundus revealed a shallow annular peripheral choroidal detachment. The suprachoroidal fluid was drained. The patient presented 3 days later with a recurrent flat chamber and an annular peripheral choroidal effusion. The fluid was removed and reinforcement of the scleral flap was performed with the resolution of the flat anterior chamber. A large corneal epithelial defect developed after the second drainage. The oral prednisone was tapered quickly and the topical steroid was decreased. One week later, his vision decreased to count fingers with severe corneal stromal edema and Descemet's membrane folds that improved to 20/50 within 24 h of resumption of the oral steroid and frequent topical steroid. The patient's visual acuity improved to 20/20 following a slow withdrawal of the oral and topical steroid. Eight months after surgery, the IOP was 15 mm Hg without glaucoma medication. The detection of a shallow anterior choroidal detachment by transverse B-scan is critical to making the correct diagnosis. Severe cornea edema can occur if the steroid is withdrawn too quickly. Thus, steroids should be tapered cautiously in steroid-dependent patients. PMID:24348402

  4. Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease.

    PubMed Central

    Okada, Y.; Shimoe, T.; Muguruma, M.; Usumoto, R.; Tsuji, T.; Jinno, K.; Moriwaki, S.; Shin, S.; Hakomori, S.

    1988-01-01

    Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3341453

  5. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice

    PubMed Central

    Sun, Ye; Fu, Zhongjie; Liu, Chi-Hsiu; Evans, Lucy; Tian, Katherine; Saba, Nicholas; Fredrick, Thomas; Morss, Peyton; Chen, Jing; Smith, Lois E. H.

    2015-01-01

    The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model. PMID:26161975

  6. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  7. Activated Conventional T-Cells Are Present in Langerhans Cell Histiocytosis Lesions Despite the Presence of Immune Suppressive Cytokines.

    PubMed

    Quispel, Willemijn T; Stegehuis-Kamp, Janine A; Santos, Susy J; Egeler, R Maarten; van Halteren, Astrid G S

    2015-10-01

    Langerhans cell histiocytosis (LCH) lesions are characterized by neoplastic CD1a(+)/Langerin(+) histiocytes (LCH-cells) and display many features of chronic inflammation. Cancer cells can escape immune-surveillance through intra-tumoral secretion of immune-suppressive cytokines. We therefore studied by immunohistochemistry the local cytokine milieu and phenotypic characteristics of T-cells and LCH-cells present in LCH lesions collected from 25 therapy naïve patients. LCH biopsies predominantly expressed interleukin-10 (IL-10) (10/25), transforming growth factor-beta (TGF-β) (9/25), or both cytokines (6/25). The absolute number of CD3(+)T-cells and the CD3(+)FOXP3(-) conventional cell (T-CONV) versus the CD3(+)FOXP3(+) regulatory T-cell (T-REG) was comparable for each suppressive cytokine profile (5:1). IL-10-expressing lesions contained, however, a higher proportion of T-CONV expressing the activation markers CD25 98% (38%-100%) and inducible costimulatory molecule (ICOS) 86% (47%-100%) than lesions wherein solely TGF-β was detected (CD25(+) 20% (6%-54%); ICOS(+) 29% (7%-51%)). Virtually all T-REG expressed CD25 and ICOS in IL-10 lesions, whereas TGF-β(+) lesions contained a lower proportion of ICOS(+) T-REG (P=0.05). IL-10(+) lesions contained more LCH-cells expressing high intensity of ICOS ligand (ICOSL) compared with TGF-β(+) lesions (P=0.03). ICOS expression by lesion-infiltrating T-CONV and T-REG positively correlated to the extent of ICOSL expression by LCH-cells (P=0.004). Our study points out that the combined detection of interlesional IL-10 and ICOSL expression by LCH-cells is associated with the highest prevalence of activated T-CONV. Immune profiling of LCH-affected tissues obtained at the time of diagnosis may set the stage for the development of new types of therapies, which aim at local boosting of immune cells that recognize and eliminate neoplastic LCH-cells. PMID:26381039

  8. Analysis of Choroidal Morphology and Vasculature in Healthy Eyes Using Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Branchini, Lauren A; Adhi, Mehreen; Regatieri, Caio V; Nandakumar, Namrata; Liu, Jonathan J; Laver, Nora; Fujimoto, James G; Duker, Jay S

    2013-01-01

    Objective To analyze the morphology and vasculature of the choroid in healthy eyes using spectral-domain optical coherence tomography (SD-OCT). Design Cross-sectional retrospective review. Participants Forty-two healthy subjects (42 eyes), with no ocular disease who underwent high-definition scanning with Cirrus HD-OCT at the New England Eye Center, Boston, Massachusetts between November 2009 and September 2010. Methods The SD-OCT images were evaluated for morphological features of the choroid, including the shape of the choroid-scleral border, location of the thickest point of choroid and regions of focal choroidal thinning. Total choroidal thickness and large choroidal vessel layer thickness were measured by two independent observers experienced in analyzing OCT images using the Cirrus linear measurement tool at the fovea, 750μm nasal and temporal to the fovea. Custom software was used to calculate the ratio of choroidal stroma to the choroidal vessel lumen. Main Outcome Measures Qualitative assessment of the choroidal morphology, quantitative analysis of choroidal vasculature and use of a novel automated software to determine the ratio of choroidal stromal area to the area of choroidal vessel lumen. Results The 42 subjects had a mean age of 51.6 years. All subjects (100%) had a “bowl” or convex shape to the choroid-sclera junction and the thickest point of the choroid was under the fovea in 88.0% of the subjects. The mean choroidal thickness was 256.8±75.8μm, thickness of the large choroidal vessel layer was 204.3±65.9μm and that of medium choroidal vessel layer/choriocapillaris layer was 52.9±20.6μm beneath the fovea. The ratio of large choroidal vessel layer thickness to the total choroidal thickness beneath the fovea was 0.7±0.06. The software generated ratio of choroidal stromal area to the choroidal vessel lumen area to be 0.27±0.08, suggesting that choroidal vessel lumen forms a greater proportion of the choroid than choroidal stroma in

  9. Pineal lesions: a multidisciplinary challenge.

    PubMed

    Westphal, Manfred; Emami, Pedram

    2015-01-01

    The pineal region is a complex anatomical compartment, harbouring the pineal gland surrounded by the quadrigeminal plate and the confluents of the internal cerebral veins to form the vein of Galen. The complexity of lesions in that region, however, goes far beyond the pineal parenchyma proper. Originating in the pineal gland, there are not only benign cysts but also numerous different tumour types. In addition, lesions such as tectal gliomas, tentorial meningiomas and choroid plexus papillomas arise from the surrounding structures, occupying that regions. Furthermore, the area has an affinity for metastatic lesions. Vascular lesions complete the spectrum mainly as small tectal arteriovenous malformations or cavernous haemangiomas.Taken together, there is a wide spectrum of lesions, many unique to that region, which call for a multidisciplinary approach. The limited access and anatomical complexity have generated a spectrum of anatomical approaches and raised the interest for neuroendoscopic approaches. Equally complex is the spectrum of treatment modalities such as microsurgery as the main option but stereotactic radiosurgery as an alternative or adjuvant to surgery for selected cases, radiation as for germinoma (see below) and or combinatorial chemotherapy, which may need to precede any other ablative technique as constituents.In this context, we review the current literature and our own series to obtain a snapshot sentiment of how to approach pineal lesions, how to interrelate alternative/competing concepts and review the recent technological advances. PMID:25411146

  10. Age-based analysis of choroidal thickness and choroidal vessel diameter in primary open-angle glaucoma.

    PubMed

    Toprak, Ibrahim; Yaylalı, Volkan; Yildirim, Cem

    2016-04-01

    We aimed to assess choroidal thickness and vessel diameter in patients with primary open-angle glaucoma (POAG) using enhanced depth imaging (EDI) optical coherence tomography (OCT) with age-based analysis. Fifty-four patients with a confirmed diagnosis of POAG and 44 age-sex matched healthy subjects were included into the study. A masked physician performed measurements of largest choroidal vessel diameter and choroidal thicknesses (subfoveal, nasal, and temporal) using EDI OCT. Subgroup analyses were performed to compare choroidal measurements based on age (with a cut point of 70 years). The study cohort comprised 54 patients with POAG (mean age of 63.2 ± 8.8 years) and 44 healthy control subjects (mean age of 62.9 ± 8.5 years) (P = 0.870). We found no significant differences in terms of choroidal measurements (P > 0.05) between the glaucoma and control groups. However, in the glaucoma group, patients with an age ≥70 years had significantly thinner subfoveal and nasal choroid compared to those of the patients with <70 years of age (P = 0.017, 0.002 respectively). In the control group, choroidal thickness and vessel measurements showed no significant difference when the subjects were subgrouped according to the age cut point (P > 0.05). Choroidal thickness and vessel caliber seem not to differ between patients with POAG and healthy controls. However, an age ≥70 years might be associated with thinning in subfoveal and nasal choroid in patients with POAG. Further studies are needed to elucidate whether choroidal thinning is a cause or result in POAG. PMID:26077882

  11. Are Neutrophil Extracellular Traps Playing a Role in the Parasite Control in Active American Tegumentary Leishmaniasis Lesions?

    PubMed Central

    Morgado, Fernanda Nazaré; Nascimento, Michelle T. C.; Saraiva, Elvira M.; de Oliveira-Ribeiro, Carla; Madeira, Maria de Fátima; da Costa-Santos, Marcela; Vasconcellos, Erica C. F.; F. Pimentel, Maria Ines; Rosandiski Lyra, Marcelo; Schubach, Armando de Oliveira; Conceição-Silva, Fátima

    2015-01-01

    Neutrophil extracellular traps (NETs) have been described as a network of extracellular fibers composed by DNA, histones and various proteins/enzymes. Studies have demonstrated that NETs could be responsible for the trapping and elimination of a variety of infectious agents. In order to verify the presence of NETs in American tegumentary leishmaniasis (ATL) and their relationship with the presence of amastigotes we evaluated active cutaneous lesions of 35 patients before treatment by the detection of parasites, neutrophils (neutrophil elastase) and histones through immunohistochemistry and confocal immunofluorescence. Intact neutrophils could be detected in all ATL lesions. NETs were present in 27 patients (median 1.1; range from 0.1 to 23.5/mm2) with lesion duration ranging from one to seven months. NETs were in close proximity with neutrophils (r = 0.586; p = 0.0001) and amastigotes (r = 0.710; p = 0.0001). Two patterns of NET formation were detected: small homogeneously distributed networks observed in all lesions; and large structures that could be visualized at a lower magnification in lesions presenting at least 20% of neutrophils. Lesions presenting the larger NET formation showed high parasite detection. A correlation between NET size and the number of intact amastigotes was observed (p=0.02). As we detected an association between NET and amastigotes, our results suggest that neutrophil migration and NET formation could be stimulated and maintained by stimuli derived from the parasite burden/parasite antigen in the extracellular environment. The observation of areas containing only antigens not intermingled with NETs (elastase and histone) suggests that the involvement of these structures in the control of parasite burden is a dynamic process in which the formation of NETs is exhausted with the destruction of the parasites. Since NETs were also associated with granulomas, this trapping would favor the activity of macrophages in order to control the parasite

  12. NSAIDs inhibit neovascularization of choroid through HO-1-dependent pathway.

    PubMed

    Yoshinaga, Narimasa; Arimura, Noboru; Otsuka, Hiroki; Kawahara, Ko-Ichi; Hashiguchi, Teruto; Maruyama, Ikuro; Sakamoto, Taiji

    2011-09-01

    Intraocular neovascularization is the leading cause of severe visual loss and anti-vascular endothelial growth factor (VEGF) therapy is currently performed for choroidal neovascularization (CNV). Despite its potent anti-angiogenic effect, there are concerns about its long-term safety. Non-steroidal anti-inflammatory drugs (NSAIDs) are common therapeutic agents used for treating inflammatory diseases, and their anti-stress effects are attracting attention now. We studied the effects of topical NSAIDs on CNV, focusing on anti-stress proteins. Cultured retinal pigment epithelium (RPE) cells were treated with NSAIDs: bromfenac, indomethacin, or vehicle control. Transcription factor NF-E2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase (HO)-1 were assessed using western blot and immunohistochemistry. As a result, NSAIDs induced translocation of Nrf2 into the nucleus and the robust expression of HO-1 in a dose- and time-dependent manner. Flow cytometric analysis revealed that bromfenac inhibited H(2)O(2)-induced apoptosis in cultured RPE cells. Next, we studied the effects of topical bromfenac on laser-induced CNV model in rat. The expressions of Nrf2 and HO-1, infiltrations of ED-1-positive macrophages at CNV lesions and size were analyzed. VEGF in the ocular fluid of these rats was also measured using enzyme-linked immunosorbent assay. Rats administered an inhibitor of HO-1 stannic mesoporphyrin (SnMP) were also studied. The results showed that topical bromfenac led to translocation of Nrf2 and induction of HO-1 in CNV lesions and that the number of infiltrating macrophages at the CNV lesion decreased. The sizes of CNV lesions were significantly smaller in bromfenac-treated rats than control CNV, and the effects were diminished by SnMP. VEGF increased in the ocular fluid after laser treatment and was inhibited by bromfenac and SnMP canceling these effects. NSAIDs inhibit CNV through the novel anti-stress protein HO-1-dependent pathway

  13. Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats.

    PubMed

    Engber, T M; Susel, Z; Kuo, S; Gerfen, C R; Chase, T N

    1991-06-21

    The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1717109

  14. Central Serous Chorioretinopathy Mistaken for Tuberculous Choroiditis

    PubMed Central

    Papadia, Marina; Herbort, Carl P.

    2011-01-01

    Purpose To report a patient erroneously diagnosed with tuberculous choroiditis who was accordingly treated with long term steroids which in turn, worsened the actual disease process that turned out to be central serous chorioretinopathy (CSC). Case Report A 59-year-old Caucasian man developed a chorioretinal disease in his right eye in 1997. Having a positive tuberculin skin test, tuberculous chorioretinitis was suspected and antituberculous therapy was administered for 4 months. In 2005, visual symptoms in the same eye recurred and despite negative interferon gamma release assay, tuberculous choroiditis was considered as the diagnosis and the patient further received massive corticosteroid therapy along with antituberculous agents. Despite a deteriorating clinical picture, therapy was continued. Upon initial examination at our center, no sign of inflammation was observed and a diagnosis of CSC was made, consequently steroid therapy was terminated. Conclusion In some chorioretinopathies, it is difficult to differentiate inflammatory from non-inflammatory causes. One should observe the course of the disease and question the initial diagnosis when no improvement or deterioration occurs despite therapy. PMID:22454755

  15. Choroid plexus macrophages proliferate and release toxic factors in response to feline immunodeficiency virus.

    PubMed

    Bragg, D C; Hudson, L C; Liang, Y H; Tompkins, M B; Fernandes, A; Meeker, R B

    2002-06-01

    Recent observations have suggested that lentiviruses stimulate the proliferation and activation of microglia. A similar effect within the dense macrophage population of the choroid plexus could have significant implications for trafficking of virus and inflammatory cells into the brain. To explore this possibility, we cultured fetal feline macrophages and examined their response to feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus for macrophage proliferation, often inducing a dramatic increase in macrophage density. Exposure to FIV resulted in a small increase in the number of macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in macrophage density after FIV infection also correlated with an increase in neurotoxic activity of the macrophage-conditioned medium. Starting at 16-18 weeks postinfection, well after the peak of viremia, a similar toxic activity was detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF increased over time and was paralleled by strong CD18 staining of macrophages/microglia in the choroid plexus and adjacent parenchyma. These results suggest that lentiviral infection of the choroid plexus can induce a toxic inflammatory response that is fueled by local macrophage proliferation. Together with the observation of increasing toxic activity in the CSF and increased CD18 staining in vivo, these observations suggest that choroid plexus macrophages may contribute to an inflammatory cascade in the brain that progresses independently of systemic and CSF viral load. PMID:12053277

  16. Gyrate atrophy of the retina and choroid. Two methods for prenatal diagnosis.

    PubMed

    O'Donnell, J J; Sipilä, I; Vannas, A; Sandman, R; Vannas-Sulonen, K

    1981-08-01

    We report two methods for prenatal diagnosis of gyrate atrophy of the retina and choroid caused by an inborn error of ornithine aminotransferase activity. A high pressure liquid chromatography assay measures ornithine aminotransferase accurately and directly in cultured amniotic fluid cells. The differential incorporation of 14C-ornithine and 3H-leucine into cell protein measures OAT directly but rapidly and simply. PMID:7298261

  17. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report

    PubMed Central

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China. PMID:26640540

  18. Metaphase I arrest and spontaneous parthenogenetic activation of strain LTXBO oocytes: chimeric reaggregated ovaries establish primary lesion in oocytes.

    PubMed

    Eppig, J J; Wigglesworth, K; Hirao, Y

    2000-08-01

    Oocytes of strain LT mice, and related strains such as LTXBO, exhibit a high incidence of arrest in the progression of meiosis at metaphase I (MI) and in spontaneous parthenogenetic activation. Activation of these oocytes within the ovary leads to the formation of ovarian teratomas. In this study, the role of the oocyte's companion granulosa cells, the cumulus cells, was investigated using fully grown oocytes matured in vitro after isolation from LTXBO mice. Results showed that the role of cumulus cells in MI arrest is dichotomous. Cumulus cells temporarily helped to sustain MI arrest, but they also promoted a delayed progression to metaphase II. Cumulus cells also promoted parthenogenetic activation that occurred in association with the delayed progression to metaphase II. Next, the question of whether the lesion(s) promoting MI arrest and spontaneous activation is due to defects in the somatic cells or is intrinsic to the oocyte was addressed using chimeric reaggregated ovaries. An improved method for completely exchanging the germ cell and the somatic cell compartments of ovaries from newborn mice is described. These chimeric reaggregated ovaries, grafted beneath the renal capsule of SCID mice, allowed the complete development of LTXBO oocytes to occur in association with somatic cells from control (B6SJLF(1)) ovaries and development of control oocytes in association with LTXBO somatic cells. Oocyte growth and follicular development appeared generally normal in reaggregated ovaries. High incidences of MI arrest and spontaneous activation of LTXBO oocytes occurred regardless of the genotype of the somatic cells. Moreover, there was a low incidence of MI arrest and spontaneous activation of control oocytes, even though they underwent complete development and maturation associated with LTXBO somatic cells. It is concluded that the phenotypes of MI arrest and parthenogenetic activation in LTXBO oocytes are defects caused by lesions intrinsic to the oocyte

  19. Choroidal and macular thickness changes induced by cataract surgery

    PubMed Central

    Falcão, Manuel S; Gonçalves, Nuno M; Freitas-Costa, Paulo; Beato, João B; Rocha-Sousa, Amândio; Carneiro, Ângela; Brandão, Elisete M; Falcão-Reis, Fernando M

    2014-01-01

    Background The aim of this study was to evaluate the effect of uneventful phacoemulsification on the morphology and thickness of the macula, the submacular choroid, and the peripapillary choroid. Methods In 14 eyes from 14 patients, retinal macular thickness, choroidal submacular thickness, and choroidal peripapillary thickness were measured preoperatively and at one week and one month after phacoemulsification using enhanced depth imaging spectral domain optical coherence tomography. Changes in thickness of the different ocular tissues were evaluated. Results There was a statistically significant increase in mean retinal macular thickness at one month. In horizontal scans, the mean increase was +8.67±6.75 μm (P<0.001), and in vertical scans, the mean increase was +8.80±7.07 μm (P=0.001). However, there were no significant changes in choroidal morphology in the submacular and peripapillary areas one month after surgery. In vertical scans, there was a nonsignificant increase in choroidal thickness (+4.21±20.2 μm; P=0.47) whilst in horizontal scans a nonsignificant decrease was recorded (−9.11±39.59 μm; P=0.41). In peripapillary scans, a nonsignificant increase in mean choroidal thickness was registered (+3.25±11.80 μm; P=0.36). Conclusion Uncomplicated phacoemulsification induces nonpathologic increases in retinal macular thickness probably due to the inflammatory insult of the surgery; however these changes are not accompanied by significant changes in choroidal thickness. In the posterior segment, the morphologic response to the inflammatory insult of phacoemulsification is mainly observed at the retinal level, and seems to be independent of choroidal thickness changes. PMID:24368877

  20. Protective activity of crocin against indomethacin-induced gastric lesions in rats.

    PubMed

    Mard, Seyyed Ali; Pipelzadeh, Mohammad Hasan; Teimoori, Ali; Neisi, Niloofar; Mojahedin, Simindokht; Khani, Maryam Zolfaghari Sabzeh; Ahmadi, Iraj

    2016-01-01

    The present study was designed to elucidate the mechanism(s) of the gastro-protective effect of crocin against indomethacin-induced gastric lesions. Crocin or pantoprazole was administered to rats 30 min before indomethacin. Five hours later, the animals were killed and their stomachs were removed and examined macroscopically. Samples of gastric mucosa were collected for microscopic evaluation, mRNA expression of caspase-3, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was quantified by RT-PCR, and protein levels of COX-1, COX-2, iNOS and caspase-3 were assessed by Western blotting. The pH, volume of gastric effluent and antioxidant activity were measured in 5 separate groups of rats following pylorus ligation. Indomethacin induced significant increases in mRNA and protein expression of iNOS and caspase-3 and increased MDA levels, and reduced the pH of the gastric effluent and protein and mRNA expression of COX-2 and protein expression of COX-1 and mucus content associated with gastric ulceration. Crocin and pantoprazole significantly inhibited mRNA and protein expression of iNOS, caspase-3 and MDA, and reduced mucus content induced by indomethacin. However, unlike pantoprazole, crocin failed to increase COX-1 and pH, but had variable increasing effects on mRNA and protein expression of COX-2. Macroscopic and microscopic observations showed that mucosal erosions induced by indomethacin were significantly inhibited by pantoprazole and crocin. These findings suggest that crocin exerts its gastro-protective effects mainly by inhibition of MDA, reduction in iNOS and caspase-3, and inhibition of the reduction in mucus content induced by indomethacin. Crocin is a novel agent that has potential in the prevention of ulceration induced by NSAIDs. PMID:26439477

  1. Failure of intravitreal bevacizumab in the treatment of choroidal metastasis

    PubMed Central

    Maudgil, A; Sears, K S; Rundle, P A; Rennie, I G; Salvi, S M

    2015-01-01

    Background Metastasis to choroid is the most common intraocular malignancy, arising most frequently from carcinoma of breast in women and lung in men. Recent case reports have described successful use of intravitreal bevacizumab to achieve local control of such tumours. Materials and methods Five cases of choroidal metastases from varying primaries: breast, lung, and colon were treated with intravitreal bevacizumab, and tumour response observed and documented with serial photographs and B-scans. Results Four of the five tumours were seen to progress despite intravitreal bevacizumab treatment. Conclusions Intravitreal bevacizumab as the primary treatment of choroidal metastases is not recommended and should not delay more effective alternative treatments. PMID:25771814

  2. Choroid plexus papilloma in a beluga whale (Delphinapterus leucas).

    PubMed

    Thomas, Christian; Mergl, June; Gehring, Erica; Paulus, Werner; Martineau, Daniel; Hasselblatt, Martin

    2016-07-01

    We report herein a choroid plexus papilloma in a beluga whale (Delphinapterus leucas). This case was positive for choroid plexus tumor marker Kir7.1 on immunohistochemistry. These results and the high conservation of Kir7.1 across species at the amino acid sequence level strongly suggest that antibodies directed against Kir7.1 not only can be employed for the diagnosis of choroid plexus tumors in cetaceans, but are also likely to be diagnostically useful in other animal species. PMID:27216722

  3. Quantitative, real-time analysis of base excision repair activity in cell lysates utilizing lesion-specific molecular beacons.

    PubMed

    Svilar, David; Vens, Conchita; Sobol, Robert W

    2012-01-01

    We describe a method for the quantitative, real-time measurement of DNA glycosylase and AP endonuclease activities in cell nuclear lysates using base excision repair (BER) molecular beacons. The substrate (beacon) is comprised of a deoxyoligonucleotide containing a single base lesion with a 6-Carboxyfluorescein (6-FAM) moiety conjugated to the 5'end and a Dabcyl moiety conjugated to the 3' end of the oligonucleotide. The BER molecular beacon is 43 bases in length and the sequence is designed to promote the formation of a stem-loop structure with 13 nucleotides in the loop and 15 base pairs in the stem. When folded in this configuration the 6-FAM moiety is quenched by Dabcyl in a non-fluorescent manner via Förster Resonance Energy Transfer (FRET). The lesion is positioned such that following base lesion removal and strand scission the remaining 5 base oligonucleotide containing the 6-FAM moiety is released from the stem. Release and detachment from the quencher (Dabcyl) results in an increase of fluorescence that is proportionate to the level of DNA repair. By collecting multiple reads of the fluorescence values, real-time assessment of BER activity is possible. The use of standard quantitative real-time PCR instruments allows the simultaneous analysis of numerous samples. The design of these BER molecular beacons, with a single base lesion, is amenable to kinetic analyses, BER quantification and inhibitor validation and is adaptable for quantification of DNA Repair activity in tissue and tumor cell lysates or with purified proteins. The analysis of BER activity in tumor lysates or tissue aspirates using these molecular beacons may be applicable to functional biomarker measurements. Further, the analysis of BER activity with purified proteins using this quantitative assay provides a rapid, high-throughput method for the discovery and validation of BER inhibitors. PMID:22895410

  4. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  5. Breast Cancer Cells Induce Osteolytic Bone Lesions In vivo through a Reduction in Osteoblast Activity in Mice

    PubMed Central

    Gregory, Laura S.; Choi, Wilson; Burke, Leslie; Clements, Judith A.

    2013-01-01

    Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone resorption activity at two time-points (18 and 36 days) during development of the bone lesion following intratibial injection of MDA-MB-231 human breast cancer cells into the left tibiae of Severely Combined Immuno-Deficient (SCID) mice. The contralateral tibia was used as a control. Tibiae were extracted and processed for undecalcified histomorphometric analysis. We provide evidence that the early bone loss observed following exposure to MDA-MB-231 cells was due to a significant reduction in mineral apposition rate, rather than increased levels of bone resorption. This suggests that osteoblast activity was impaired in the presence of breast cancer cells, contrary to previous reports of osteoclast-dependent bone loss. Furthermore mRNA expression of Dickkopf Homolog 1 (DKK-1) and Noggin were confirmed in the MDA-MB-231 cell line, both of which antagonise osteoblast regulatory pathways. The observed bone loss following injection of cancer cells was due to an overall thinning of the trabecular bone struts rather than perforation of the bone tissue matrix (as measured by trabecular width and trabecular separation, respectively), suggesting an opportunity to reverse the cancer-induced bone changes. These novel insights into the mechanisms through which osteolytic bone lesions develop may be important in the development of new treatment strategies for metastatic breast cancer

  6. Lesions of anterior thalamic nuclei impair acquisition of new and changing of preoperatively learnt active avoidance stereotypes.

    PubMed

    Klingberg, F; Klingberg, H

    1988-01-01

    Six-month-old male Long-Evans rats reproduced their preoperatively learnt active avoidance responses (CAR) in a Y-maze and in a jump test box after bilateral symmetric lesions of thalamic anterior ventral (AV) and anterior medial (AM) nuclei without significant changes. However, when the test sequence was changed in a way that transitions from high success probability (low error probability) to low success probability (high error probability) were taken into account, then problems with time limit and increased punishments were not overcome by lesioned rats. Transitions in the opposite direction were better mastered. All AV-AM rats were unable to acquire a new CAR stereotype in a W-like maze in which the first phase had a low success probability. Rats without lesions were rarely influenced by various test sequences. The lesioned rats showed purely arrest behaviour and did not develop learned helplessness in successless sessions and were transiently hyperactive in the open field test. The data support the hypothesis that the anterior thalamic nuclei as part of the Papez circuit participate in the analysis of success probability and preferent consolidation of correct responses, when stereotype behaviour has to be changed. PMID:3240299

  7. Encapsulated living choroid plexus cells: potential long-term treatments for central nervous system disease and trauma

    NASA Astrophysics Data System (ADS)

    Skinner, S. J. M.; Geaney, M. S.; Lin, H.; Muzina, M.; Anal, A. K.; Elliott, R. B.; Tan, P. L. J.

    2009-12-01

    In neurodegenerative disease and in acute brain injury, there is often local up-regulation of neurotrophin production close to the site of the lesion. Treatment by direct injection of neurotrophins and growth factors close to these lesion sites has repeatedly been demonstrated to improve recovery. It has therefore been proposed that transplanting viable neurotrophin-producing cells close to the trauma lesion, or site of degenerative disease, might provide a novel means for continuous delivery of these molecules directly to the site of injury or to a degenerative region. The aim of this paper is to summarize recent published information and present new experimental data that indicate that long-lasting therapeutic implants of choroid plexus (CP) neuroepithelium may be used to treat brain disease. CP produces and secretes numerous biologically active neurotrophic factors (NT). New gene microarray and proteomics data presented here indicate that many other anti-oxidant, anti-toxin and neuronal support proteins are also produced and secreted by CP cells. In the healthy brain, these circulate in the cerebrospinal fluid through the brain and spinal cord, maintaining neuronal networks and associated cells. Recent publications describe how transplanted CP cells and tissue, either free or in an immunoprotected encapsulated form, can effectively deliver therapeutic molecules when placed near the lesion or site of degenerative disease in animal models. Using simple techniques, CP neuroepithelial cell clusters in suspension culture were very durable, remaining viable for 6 months or more in vitro. The cell culture conditions had little effect on the wide range and activity of genes expressed and proteins secreted. Recently, completed experiments show that implanting CP within alginate-poly-ornithine capsules effectively protected these xenogeneic cells from the host immune system and allowed their survival for 6 months or more in the brains of rats, causing no adverse effects

  8. Comparison Between Biofilm Production, Phospholipase and Haemolytic Activity of Different Species of Candida Isolated from Dental Caries Lesions in Children

    PubMed Central

    Shenoy, Neetha

    2016-01-01

    Introduction C.albicans is the most commonly isolated fungal pathogen in the oral cavity, but isolation of non-albicans Candida is increasing in recent years. We wish to demonstrate the virulence factors of Candida spp. isolated from the dental caries lesion of the children as presence of virulence factors determines the pathogenic potential of any microorganism. Aim To compare biofilm production, phospholipase and haemolytic activity of C.albicans with that of non-albicans species of Candida isolated from dental caries lesions of children to evaluate the role of non- albicans species of Candida in formation of dental caries. Materials and Methods Oral swabs were collected from caries lesion of 100 school children of age 5-10 years with dental caries. Candida isolates were tested for biofilm production, phospholipase and haemolytic activity. Statistical analysis was done by Chi-Square test and Mann-Whitney U test wherever applicable using SPSS version 11.5. Results Out of the 100 children with dental caries 37 were positive for Candida by smear or culture and 31 by culture. C.albicans was the most prevalent isolate followed by C.krusei, C.tropicalis and C.albicans. Out of 21 C.albicans isolates, 10 (47.6%) showed phospholipase activity and 18 (85.71%) produced biofilm. Of the 10 non-albicans strains, 5 (50%) showed phospholipase activity and 6 (60%) produced biofilm. All isolates of Candida produced haemolysin (100%). Conclusion There was no statistically relevant difference between the virulence factor production by C.albicans and non-albicans species of Candida. In other words, our study shows that both C.albicans and non-albicans species of Candida isolated from caries lesions of the children, produce these virulence factors. So we can say that non-albicans species of Candida also are involved in caries formation. PMID:27190803

  9. Photodynamic therapy for unilateral idiopathic peripapillary choroidal neovascularization in a child.

    PubMed

    Yıldırım, Cem; Çetin, Ebru Nevin; Yayla, Kemal; Avunduk, Avni Murat; Yaylalı, Volkan

    2011-08-01

    A 10-year-old girl presented with visual loss in her right eye. Best-corrected visual acuity was 20/50 in the right eye and 20/20 in the left eye. Dilated funduscopic examination revealed a yellowish elevated lesion near the optic disc with macular edema and hemorrhage on the inferotemporal vascular arcade in the right eye. Fluorescein angiography showed a hyperfluorescent lesion consistent with choroidal neovascularization (CNV) and optical coherence tomography (OCT) showed a peripapillary lesion with subretinal fluid elevating the neurosensory retina in the macular area. With a diagnosis of unilateral idiopathic peripapillary CNV, the patient underwent photodynamic therapy (PDT) with verteporfin. At the four month follow-up, visual acuity increased to 20/25 and OCT showed peripapillary scar formation and total resolution of the subretinal fluid. At the one year follow-up, visual acuity and fundus were stable without recurrence of the lesion. PDT for peripapillary CNV in children has not previously been reported. Although it seems to be a favorable treatment option for peripapillary lesions, there is a lack of knowledge about long-term follow-up in pediatric cases. PMID:21637978

  10. Choroid Metastasis from Testicular Carcinoma: A Rare Entity.

    PubMed

    Singh, Dig Vijay; Gupta, Vishali; Singh, Shrawan Kumar

    2016-01-01

    The aim of this report is to contribute to the clinical understanding of choroid metastasis from testicular carcinoma. A young male patient presented with loss of vision in his left eye with ptosis and proptosis. Fundoscopy revealed bullous retinal detachment with dark hazy vitreous. The preliminary diagnosis of choroid carcinoma with vitreous involvement was made by an ophthalmologist. Later in the physical examination, there was a firm painless left testicular swelling. Testicular tumor markers were raised. Based on ultrasonography, MRI and PET-CT, a clinical diagnosis of left testicular carcinoma metastasizing to the left choroid and vitreous was made. A mixed germ cell tumor was reported on histopathological examination. After cisplatin-based chemotherapy, serum tumor markers normalized and vision improved. Exceptional choroidal and vitreous metastases with absence of other visceral and bony involvement constituted the presenting sign. Although rare, testicular carcinoma must be considered to metastasize to the eye, especially if loss of vision is the chief complaint. PMID:23969474

  11. A mixed choroid plexus papilloma and ependymoma.

    PubMed

    Lee, Yujin; Kim, Seong Ik; Kim, Seung-Ki; Kim, In One; Park, Sung-Hye

    2016-04-01

    We report a novel case of a mixed choroid plexus papilloma (CPP) and ependymoma with cartilaginous differentiation. This kind of mixed tumor has not been previously reported in the English literature. The patient was a 5-year-old girl, who presented with a 1-week history of fever and numbness of the right lower limb. Magnetic resonance imaging of the brain with gadolinium revealed a heterogeneously enhancing mass in the occipital horn of the left lateral ventricle. Histologically, the tumor showed an intermixed CPP area and a low-grade papillary ependymoma-like area, which was studded with cartilage islands and psammoma bodies. In many foci, direct transition of CPP and ependymoma was observed, but there were no high-grade features. We report this novel case, describe the unique microscopic and immunohistochemical features, and speculate on the pathogenesis. PMID:26670168

  12. Treatment of choroid hemangioma with argon laser

    NASA Astrophysics Data System (ADS)

    Yang, Chuanzhu; Song, Man

    1993-03-01

    The treatment effects of 7 cases of choroid hemangioma are reported. Of them, 4 cases were men and 3 cases were women. Ages varied from 34 to 52 years. The mean age was 43 years. All of their eyesight was between 0.01 and 0.4. Six of the seven cases were solitary hemangioma, the other one was Sturge-Weber syndrome. After treatment photography, the color of the hemangioma body gradually got weak and the local presented pigmentation. The results of the fluorescein fundus angiography indicated that the hemangioma body reduced, then got atrophy and fibrosis. In five cases eyesight increased, and it didn't in the other two cases.

  13. Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

    PubMed Central

    2010-01-01

    Background The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the non-injured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases PMID:20184752

  14. Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia

    PubMed Central

    Lim, Young H.; Ovejero, Diana; Sugarman, Jeffrey S.; DeKlotz, Cynthia M.C.; Maruri, Ann; Eichenfield, Lawrence F.; Kelley, Patrick K.; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J.; Gafni, Rachel I.; Boyce, Alison M.; Cowen, Edward W.; Bhattacharyya, Nisan; Guthrie, Lori C.; Gahl, William A.; Golas, Gretchen; Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.; Levy, Moise L.; Collins, Michael T.; Choate, Keith A.

    2014-01-01

    Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23. PMID:24006476

  15. Treatment of choroidal neovascularization in high myopia.

    PubMed

    Montero, Javier A; Ruiz-Moreno, Jose M

    2010-05-01

    High myopia affects approximately 2% of general population, and is a major cause of legal blindness in many developed countries. Choroidal neovascularization (CNV) is the most common vision-threatening complication of high myopia. Different therapeutic approaches have been attempted such as thermal laser photocoagulation, surgery and photodynamic therapy with verteporfin (PDT). The visual outcome of these therapies has been reported to be better than the natural history of the condition. However, the limited visual acuity improvement after PDT monotherapy and the appearance of subretinal fibrosis and chorioretinal atrophy prompted the association of other therapies. In the past few years a tremendous advance in the knowledge of the mechanisms underling CNV secondary to high myopia and age related macular degeneration has been achieved, leading to new therapeutic targets and novel drugs and combined therapies. These new therapeutic weapons have been designed to achieve a selective shut down of choroidal new vessels. Recent reviews have been published on the natural history and therapies for myopic CNV. Ohno-Matsui reported on the natural history of the condition as well as the outcome of laser photocoagulation, surgical extraction of CNV, foveal translocation and photodynamic therapy on myopic CNV in the short-term. Soubrane et al reviewed the new advances on surgery, laser photocoagulation and PDT, considering some of the potential effects of triamcinolone, pegaptanib and ranibizumab in CNV secondary to age related macular degeneration (AMD). Novack et al reported on the pharmacological therapy of CNV in AMD. The aim of this review is to summarize the recent advances in myopic CNV pathophysiology and the new therapeutic targets and drugs that are changing the clinical management of myopic CNV. PMID:20196722

  16. Uncommon presentation of choroid plexus papilloma in an infant

    PubMed Central

    Pandey, Sharad; Sharma, Vivek; Singh, Kulwant; Ghosh, Amrita; Gupta, Praveen Kumar

    2016-01-01

    Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension. PMID:27195037

  17. Retino-choroidal ischemia in central retinal vein occlusion

    PubMed Central

    Hussain, Nazimul; Hussain, Anjli

    2014-01-01

    A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia. PMID:25473353

  18. Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion.

    PubMed

    Plenchette, S; Moutet, M; Benguella, M; N'Gondara, J P; Guigner, F; Coffe, C; Corcos, L; Bettaieb, A; Solary, E

    2001-10-01

    Platelet transfusion is widely used to prevent bleeding in patients with severe thrombocytopenia. The maximal storage duration of platelet concentrates is usually 5 days, due to the platelet storage lesion that impairs their functions when stored for longer times. Some of the morphological and biochemical changes that characterize this storage lesion are reminiscent of cell death by apoptosis. The present study analyzed whether proteins involved in nucleated cell apoptosis could play a role in the platelet storage lesion. Storage of leukocyte-depleted platelets obtained by apheresis is associated with a late and limited activation of caspases, mainly caspase-3. This event correlates with an increased expression of the pro-apoptotic BH3-only protein Bim in the particulate fraction and a slight and late release of the pro-apoptotic mitochondrial protein Diablo/Smac in the cytosol. Platelets do not express the death receptors Fas, DR4 and DR5 on their plasma membrane, while the expression of the decoy receptor DcR2 increases progressively during platelet storage. Addition of low concentrations of the cryoprotector dimethylsulfoxide accelerates platelet caspase activation during storage, an effect that is partially prevented by the caspase inhibitor z-VAD-fmk. Altogether, DcR2 expression on the plasma membrane is an early event while caspase activation is a late event during platelet storage. These observations suggest that caspases are unlikely to account for the platelet storage lesion. As a consequence, addition of caspase inhibitors may not improve the quality of platelet concentrates stored in standard conditions. PMID:11587215

  19. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium

    PubMed Central

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an “inverse” configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this

  20. T-Lymphocytes Traffic into the Brain across the Blood-CSF Barrier: Evidence Using a Reconstituted Choroid Plexus Epithelium.

    PubMed

    Strazielle, Nathalie; Creidy, Rita; Malcus, Christophe; Boucraut, José; Ghersi-Egea, Jean-François

    2016-01-01

    An emerging concept of normal brain immune surveillance proposes that recently and moderately activated central memory T lymphocytes enter the central nervous system (CNS) directly into the cerebrospinal fluid (CSF) via the choroid plexus. Within the CSF space, T cells inspect the CNS environment for cognate antigens. This gate of entry into the CNS could also prevail at the initial stage of neuroinflammatory processes. To actually demonstrate T cell migration across the choroidal epithelium forming the blood-CSF barrier, an in vitro model of the rat blood-CSF barrier was established in an "inverse" configuration that enables cell transmigration studies in the basolateral to apical, i.e. blood/stroma to CSF direction. Structural barrier features were evaluated by immunocytochemical analysis of tight junction proteins, functional barrier properties were assessed by measuring the monolayer permeability to sucrose and the active efflux transport of organic anions. The migratory behaviour of activated T cells across the choroidal epithelium was analysed in the presence and absence of chemokines. The migration pathway was examined by confocal microscopy. The inverse rat BCSFB model reproduces the continuous distribution of tight junction proteins at cell margins, the restricted paracellular permeability, and polarized active transport mechanisms, which all contribute to the barrier phenotype in vivo. Using this model, we present experimental evidence of T cell migration across the choroidal epithelium. Cell migration appears to occur via a paracellular route without disrupting the restrictive barrier properties of the epithelial interface. Apical chemokine addition strongly stimulates T cell migration across the choroidal epithelium. The present data provide evidence for the controlled migration of T cells across the blood-CSF barrier into brain. They further indicate that this recruitment route is sensitive to CSF-borne chemokines, extending the relevance of this

  1. Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium

    PubMed Central

    Young, Robin K.

    2013-01-01

    The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a “sink” for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl2). At 50–1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [3H]choline. However, extended exposure to 250–500 nM cadmium increased [3H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase. PMID:24401988

  2. A survey of survival and activity of citrus canker lesion populations on foliage, fruit and shoots in a Florida grapefruit orchard in 2009 and 2010

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Citrus canker (Xanthomonas citri subsp. citri (Xcc)) can infect several species of citrus. The disease can develop on the leaves, shoots and fruit, causing erumpent lesions, that on fruit precludes sale to the fresh market. We assessed lesion activity in orchard-grown grapefruit to provide informa...

  3. Nandrolone decanoate and resistance exercise training favor the occurrence of lesions and activate the inflammatory response in the ventral prostate.

    PubMed

    Gomes, F C; Chuffa, L G A; Scarano, W R; Pinheiro, P F F; Fávaro, W J; Domeniconi, R F

    2016-05-01

    Age is a key factor in the development of prostatic lesions. An increase in reactive oxygen species levels occurs during aging. Furthermore, the indiscriminate use of anabolic androgenic steroids and physical exercise alter the availability of hormones and may promote the appearance of lesions. This study examined whether the use of nandrolone decanoate (ND), associated or not with resistance exercise training, affects the pathways related to the inflammatory response in the ventral prostate of adult and aged rats. Sprague-Dawley rats were distributed into eight experimental groups: sedentary with ND, sedentary without ND, exercise with ND, and exercise without ND. The animals performed resistance exercise training and received ND two times/week (5 mg/kg, i.m.) for 8 weeks. Adult rats were killed immediately following treatment completion, and aged rats remained untreated until reaching 300 days of age. The adult animals that received ND and performed resistance exercise training showed a higher occurrence of lesions with TLR4 activation. Marked IL-6 expression occurred in the group that performed resistance exercise training. The group exposed to ND showed overexpression of TLR2, TLR4, NOX1, Nrf2, TNF-α, and P38MAPK. The animals that received ND and performed training showed increase levels of NFκB, IRF3, IL-6, TNF-α, and NOX1. TLR2 and TLR4 showed no upregulation in the aged animals. The groups exercise + ND showed lesions in the adult stage and after aging, followed by molecular alterations. We concluded that nandrolone decanoate and resistance exercise training can promote the onset of prostatic tumors in the adult stage, and during aging, activating pathways involved in the inflammatory response. PMID:27011054

  4. Unique Presentation of Cerebellopontine Angle Choroid Plexus Papillomas: Case Report and Review of the Literature

    PubMed Central

    Anderson, Mark; Babington, Parker; Taheri, Reza; Diolombi, Mairo; Sherman, Jonathan H.

    2013-01-01

    Objectives We present the case of a choroid plexus papilloma (CPP) in the cerebellopontine angle (CPA), describe the different appearances of CPPs with a variety of imaging techniques, and discuss the differential diagnosis of CPA tumors. Participant and Design We report the case of a 52-year-old woman with headache, tinnitus, and unilateral hearing impairment whose preoperative magnetic resonance imaging revealed a heterogeneously enhancing CPA mass that extended into the internal auditory canal. Main Outcome Measures, Results, and Conclusion The preoperative imaging appearance of the lesion was most consistent with that of a schwannoma. Postoperative histopathologic examination found the tumor to be a CPP with cuboidal epithelial cells overlying fibrovascular stroma. CPPs are rare benign central nervous system neoplasms arising from choroid plexus epithelium. The most common site of presentation is in the fourth ventricle in adults and the lateral ventricles in children. CPPs rarely occur in the CPA, and when they do, clinical-radiologic diagnosis is difficult due to both the rarity of this presentation and to nonspecific radiological features. PMID:25083384

  5. Intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks: A report of two patients

    PubMed Central

    Ozkaya, Abdullah; Alkin, Zeynep; Faiz, Miray; Yazici, Ahmet Taylan; Demirok, Ahmet

    2013-01-01

    The aim of this study is to report clinical course of choroidal neovascularization secondary to angioid streaks (AS) in two patients who underwent intravitreal bevacizumab therapy. Fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT) revealed the diagnosis of subfoveal classic choroidal neovascularization (CNV) in the right eye in patient 1 and in the left eye in patient 2. After three consecutive bevacizumab injections, visual acuity improved from 20/40 to 20/25 in patient 1 and from 20/80 to 20/50 in patient 2. After 3 months of therapy, additional bevacizumab injection was administered when the lesion showed recurrence. After a follow-up time of 24-months, patient 1 received 14 intravitreal bevacizumab injections; patient 2 received only 4 injections. Visual acuities remained stable at 20/32 and 20/50 in patient 1 and patient 2, respectively. Though, the patients of CNV secondary to AS showed similar clinical appearance at the beginning, this report provides the data for different responses to intravitreal bevacizumab therapy. While fewer injections were required to control the disease in one patient, the other patient needed much more injections for stabilization of the CNV. Further studies are required to understand the cause of varied treatment responses in those patients. PMID:25473350

  6. Histopathologic Findings in the Areas of Orange Pigment Overlying Choroidal Melanomas

    PubMed Central

    Garcia, Maria D.; Salomao, Diva R.; Marmorstein, Alan D.; Pulido, Jose S.

    2016-01-01

    Purpose Orange pigment is an important sign of malignancy in melanocytic tumors. There is a question as to whether the pigment accumulation is inside of macrophages or retinal pigment epithelial (RPE) cells. We investigated which cells are involved with this color alteration. Methods We examined enucleated specimens from two patients with choroidal melanoma and dense orange pigment on fundus examination. Color fundus and fundus autofluorescence (FAF) photographs were reviewed followed by examination with fluorescent microscopy, electron microscopy, and immunohistochemistry of enucleated eyes for the specific areas corresponding to the orange pigment. Results Orange pigment was observed on color fundus photography and correlated with areas of hyperautofluorescence on FAF. Fluorescent microscopy of sections of the enucleated eyes showed autofluorescence in the RPE, which were most pronounced where there was a localized retinal detachment and reactive hyperplasia of the RPE. Immunohistochemical studies were done with keratin (OSCAR and AE1/AE3) and S-100 stained RPE cells, which still were attached to Bruch's membrane. Histiocytes present in the detached retina stained with anti-CD163 antibody and did not show autofluorescence. Electron microscopy studies of the same areas showed the presence of lipofuscin and melanolipofuscin within the clustered RPE cells. Conclusions Orange pigment in choroidal melanocytic lesions originates from the RPE cells, rather than macrophages, and is most abundant where there is proliferation of the RPE. Translational Relevance The orange pigment tumoral biomarker arises and is in the retinal pigment epithelium. PMID:27190699

  7. Radiation-induced malignant meningioma following proton beam therapy for a choroidal melanoma.

    PubMed

    Scaringi, Claudia; Minniti, Giuseppe; Bozzao, Alessandro; Giangaspero, Felice; Falco, Teresa; Greco, Alessandro; De Sanctis, Vitaliana; Romano, Andrea; Enrici, Riccardo Maurizi

    2015-06-01

    We report a woman with malignant meningioma diagnosed 9 years after the treatment of a choroidal melanoma with proton beam therapy. The risk of secondary cancers is a well-known adverse late effect of radiation therapy, especially with the use of advanced techniques such as intensity-modulated radiation therapy. However, this risk may be less with the use of proton beam therapy. A 79-year-old woman presented with symptoms of enophthalmos, ptosis and paralysis of the left medial rectus muscle. She had previously been successfully treated for a choroidal melanoma of the left eye with proton beam therapy (total dose: 60 cobalt gray equivalents) following local resection. MRI showed a lesion in the left cavernous sinus with extension into the orbit and a subsequent biopsy revealed a papillary meningioma. The cavernous tumor was treated with photon radiotherapy (total dose: 54Gy) which achieved an initial partial response. However, 8 months later the tumor extensively metastasized to the skull and the spine and the patient died 1 year after the treatment. The incidence of secondary malignancies after proton beam therapy is low but not negligible, therefore, it must be taken into account when planning a treatment as secondary tumors may present with a highly aggressive behaviour. PMID:25861886

  8. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide

    PubMed Central

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P.; Telander, David G.; Hjelmeland, Leonard M.; Morse, Lawrence S.

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. PMID:27429799

  9. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide.

    PubMed

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P; Telander, David G; Hjelmeland, Leonard M; Morse, Lawrence S

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in "Circadian Rhythm Signaling" pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in "Calcium Signaling" (1 week) and "Glutamate Receptor Signaling" pathways (1 month). In contrast, dexamethasone (Dex) affected the "GABA Receptor Signaling" (1 week) and "Serotonin Receptor Signaling" (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. PMID:27429799

  10. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1.

    PubMed

    Peterson, Lynda J; Wittchen, Erika S; Geisen, Pete; Burridge, Keith; Hartnett, M Elizabeth

    2007-04-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that "contact" with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  11. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

    PubMed Central

    Peterson, Lynda J.; Wittchen, Erika S.; Geisen, Pete; Burridge, Keith; Hartnett, M. Elizabeth

    2008-01-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that “contact” with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  12. Lesion-induced and activity-dependent structural plasticity of Purkinje cell dendritic spines in cerebellar vermis and hemisphere.

    PubMed

    Gelfo, Francesca; Florenzano, Fulvio; Foti, Francesca; Burello, Lorena; Petrosini, Laura; De Bartolo, Paola

    2016-09-01

    Neuroplasticity allows the brain to encode experience and learn behaviors, and also to re-acquire lost functions after damage. The cerebellum is a suitable structure to address this topic because of its strong involvement in learning processes and compensation of lesion-induced deficits. This study was aimed to characterize the effects of a hemicerebellectomy (HCb) combined or not with the exposition to environmental enrichment (EE) on dendritic spine density and size in Purkinje cell proximal and distal compartments of cerebellar vermian and hemispherical regions. Male Wistar rats were housed in enriched or standard environments from the 21st post-natal day (pnd) onwards. At the 75th pnd, rats were submitted to HCb or sham lesion. Neurological symptoms and spatial performance in the Morris water maze were evaluated. At the end of testing, morphological analyses assessed dendritic spine density, area, length, and head diameter on vermian and hemispherical Purkinje cells. All hemicerebellectomized (HCbed) rats showed motor compensation, but standard-reared HCbed animals exhibited cognitive impairment that was almost completely compensated in enriched HCbed rats. The standard-reared HCbed rats showed decreased density with augmented size of Purkinje cell spines in the vermis, and augmented both density and size in the hemisphere. Enriched HCbed rats almost completely maintained the spine density and size induced by EE. Both lesion-induced and activity-dependent cerebellar plastic changes may be interpreted as "beneficial" brain reactions, aimed to support behavioral performance rescuing. PMID:26420278

  13. Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

    PubMed Central

    Cooke, Gillian E.; Wetter, Nathan C.; Banducci, Sarah E.; Mackenzie, Michael J.; Zuniga, Krystle E.; Awick, Elizabeth A.; Roberts, Sarah A.; Sutton, Brad P.; McAuley, Edward; Kramer, Arthur F.

    2016-01-01

    Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment. PMID:26915025

  14. Choroidal Metastasis of Papillary Thyroid Carcinoma Demonstrated on SPECT-CT.

    PubMed

    Torun, Nese; Reyhan, Mehmet; Yapar, Ali Fuat; Karatas, Muge

    2016-05-01

    We report a 68-year-old woman with papillary thyroid carcinoma metastasizing to choroid. The choroid metastasis was diagnosed with SPECT-CT and then was treated with high-dose radioactive iodine therapy. PMID:26825205

  15. Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis.

    PubMed

    Shin, D M; Kim, J; Ro, J Y; Hittelman, J; Roth, J A; Hong, W K; Hittelman, W N

    1994-01-15

    With the goal of identifying a potential intermediate biomarker in the multistep process of head and neck cancer development, we conducted immunohistochemical analyses for p53 expression in 33 patients with head and neck squamous cell carcinomas whose tissue sections contained adjacent normal epithelium, hyperplastic, and/or dysplastic lesions. Fifteen of 33 (45%) squamous cell carcinomas of the head and neck expressed p53, but none of four normal control patients (cancer-free nonsmokers) expressed detectable p53 in oral mucosa specimens. To determine when p53 expression is initiated during head and neck tumorigenesis, we examined the normal and premalignant lesions adjacent to the tumors. Five of 24 (21%) samples of normal epithelium adjacent to tumors, 7 of 24 (29%) samples of hyperplasia, and 9 of 20 (45%) samples of dysplasia expressed p53. Quantitative image analysis demonstrated not only a gradual increase in the amount of p53 expression as tissue abnormalities progressed but also a topological change in expression. Whereas p53 expression, when present, was limited to the basal layer in normal epithelium adjacent to tumor, the expression of p53 expanded into the parabasal and superficial layers in hyperplasia and dysplasia. We conclude that p53 expression can be altered in very early phases of head and neck tumorigenesis. Thus, it may be an excellent candidate for risk assessment and may serve as an intermediate biomarker in chemoprevention trials. PMID:8275461

  16. Increased macular choroidal blood flow velocity during systemic corticosteroid therapy in a patient with acute macular neuroretinopathy

    PubMed Central

    Hashimoto, Yuki; Saito, Wataru; Mori, Shohei; Saito, Michiyuki; Ishida, Susumu

    2012-01-01

    Purpose The precise mechanism causing outer retinal damage in acute macular neuroretinopathy (AMN) remains unclear. In this study, choroidal blood flow velocity was quantitatively evaluated using laser speckle flowgraphy (LSFG) in a patient with AMN who received systemic corticosteroid therapy. Methods Corticosteroids were systemically administrated across 4 months for an AMN patient. LSFG measurements were taken ten consecutive times before treatment and at 1 week and 1, 3, and 10 months after the onset of therapy. The square blur rate, a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Square 1, the macular lesion with findings of severe multifocal electroretinography amplitude reduction, and Squares 2 and 3, funduscopically normal-appearing retinal areas with findings of moderate and mild multifocal electroretinography amplitude reduction, respectively. Results The AMN lesion gradually decreased after treatment and improved results were detected on the Amsler chart, as well as on optical coherence tomography and scanning laser ophthalmoscopy. When the changing rates of the macular flow were compared with the mean square blur rate level before treatment (100%), 14.6%, 24.5%, 12.9%, and 16.3% increases were detected in Square 1 (macular lesion) at 1 week and 1, 3, and 10 months after treatment, respectively. Similarly, in Square 2 (normal-appearing area next to the lesion), 12.6%, 18.6%, 6.7%, and 8.3% increases were also noted at 1 week and 1, 3, and 10 months after treatment, respectively. In Square 3 (normal-appearing area apart from the lesion), 16.0%, 15.1%, 19.1%, and 3.8% increases were measured at 1 week and 1, 3, and 10 months after treatment, respectively. Conclusion In a patient with AMN, choroidal blood flow velocity at the lesion site, which was examined with LSFG, sequentially increased during systemic corticosteroid therapy, together with improvement of visual function. The present findings suggest that

  17. A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors

    SciTech Connect

    Daftari, I. K.; Petti, P. L.; Larson, D. A.; O'Brien, J. M.; Phillips, T. L.

    2009-03-15

    A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

  18. Gamma Knife Radiosurgery for Choroidal Hemangioma

    SciTech Connect

    Kim, Yun Taek; Kang, Se Woong; Lee, Jung-Il

    2011-12-01

    Purpose: Patients with choroidal hemangioma (CH), a benign ocular hamartoma, frequently presents with visual disturbance as a result of exudative retinal detachment (RD), which originates in subretinal fluid accumulation. We report our experience using the Leksell Gamma Knife in the management of symptomatic CH. Methods and Materials: Seven patients with symptomatic CH (circumscribed form in 3 patients and diffuse form in 4) were treated with the Leksell Gamma Knife at our institution during a 7-year period. All patients presented with exudative RD involving the macula that resulted in severe visual deterioration. The prescription dose to the target margin was 10 Gy in all cases. The mean tumor volume receiving the prescription dose was 536 mm{sup 3} (range, 151-1,057). The clinical data were analyzed in a retrospective fashion after a mean follow-up of 34.4 months (range, 9-76). Results: The resolution of exudative RD was achieved within 6 months, and the visual acuity of the affected eye had improved at the latest follow-up examination (p = .018) in all patients. No recurrence of exudative RD occurred. Thinning of the CHs was observed in most patients; however, symptomatic radiation toxicity had not developed in any of the patients. Conclusion: Symptomatic CHs can be safely and effectively managed with Gamma Knife radiosurgery using a marginal dose of 10 Gy.

  19. Peripapillary choroidal thickness in healthy Turkish subjects

    PubMed Central

    Erbagci, Hulya; Oren, Burak; Okumus, Seydi; Kenan, Serhat; Celemler, Pelin; Erbagci, Ibrahim

    2015-01-01

    Aim The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT), measured by enhanced depth imaging optical coherence tomography (EDI-OCT), in healthy Turkish volunteers. Materials and methods In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. Results The mean age of the 25 female and 32 male patients in the study was 30.9±10.6 years (range, 18–56 years). The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225±57, 183±47, 220±57, and 233±59 μm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all), whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. Conclusion The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. PMID:26257510

  20. PRIMARY CULTURE OF CHOROIDAL EPITHELIAL CELLS: CHARACTERIZATION OF AN IN VITRO MODEL OF BLOOD-CSF BARRIER

    PubMed Central

    ZHENG, WEI; ZHAO, QIUQU; GRAZIANO, JOSEPH H.

    2016-01-01

    Summary A primary rat choroidal epithelial cell culture system was developed to investigate mechanisms of heavy metal toxicity on the blood-cerebrospinal fluid (CSF) barrier. Epithelial cells were dissociated from choroidal tissue by pronase digestion and cultured in standard DMEM culture media supplemented with 10% fetal bovine serum and 10 ng epithelial growth factor per ml. The procedure yielded 2–5 × 104 cells from pooled plexuses of three to four rats, and a viability of 77–85%. The cultures displayed a dominant polygonal type of epithelial cells, with a population doubling time of 2–3 d. The cultures were of distinct choroidal epithelial origins. For example, immunocytochemical studies using monospecific rabbit anti-rat TTR polyclonal antibody revealed a strong positive stain of transthyretin (TTR), a thyroxine transport protein exclusively produced by the choroidal epithelia. Also, reverse-transcriptase polymerase chain reaction (PCR) confirmed the presence of specific TTR mRNA in the cultures. The cultures were further adapted to grow on a freely permeable membrane sandwiched between two culture chambers. The formation of an impermeable confluent monolayer occurred within 5 d after seeding and was verified by the presence of a steady electrical resistance across the membrane (80 ± 10 ohm per cm2). The epithelial barriers appeared to actively transport [125I]-thyroxine from the basal to apical chamber. These results suggest that this primary cell culture system possesses typical choroidal epithelial characteristics and appears to be a suitable model for in vitro mechanistic investigations of blood–CSF barrier. PMID:9542634

  1. Event-related oscillations (ERO) during an active discrimination task: Effects of lesions of the nucleus basalis magnocellularis.

    PubMed

    Sanchez-Alavez, Manuel; Ehlers, Cindy L

    2016-05-01

    The cholinergic system in the brain is involved in attentional processes that are engaged for the identification and selection of relevant information in the environment and the formation of new stimulus associations. In the present study we determined the effects of cholinergic lesions of nucleus basalis magnocellularis (NBM) on amplitude and phase characteristics of event related oscillations (EROs) generated in an auditory active discrimination task in rats. Rats were trained to press a lever to begin a series of 1kHz tones and to release the lever upon hearing a 2kHz tone. A time-frequency based representation was used to determine ERO energy and phase synchronization (phase lock index, PLI) across trials, recorded within frontal cortical structures. Lesions in NBM produced by an infusion of a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) resulted in (1) a reduction of the number of correct behavioral responses in the active discrimination task, (2) an increase in ERO energy in the delta frequency bands, (3) an increase in theta, alpha and beta ERO energy in the N1, P3a and P3b regions of interest (ROI), and (4) an increase in PLI in the theta frequency band in the N1 ROIs. These studies suggest that the NBM cholinergic system is involved in maintaining the synchronization/phase resetting of oscillations in different frequencies in response to the presentation of the target stimuli in an active discrimination task. PMID:25660307

  2. Choroidal thickness changes in patients with pseudoexfoliation syndrome.

    PubMed

    Zengin, Mehmet Ozgur; Cinar, Esat; Karahan, Eyyup; Tuncer, Ibrahim; Yilmaz, Sami; Kocaturk, Tolga; Kucukerdonmez, Cem

    2015-08-01

    To evaluate the choroidal thickness using spectral-domain optical coherence tomography (OCT) in patients with pseudoexfoliation syndrome (PXS) and to compare them with healthy controls. This observational comparative study consisted of 35 PXS patients and 35 age- and sex-matched control cases. The control cases had neither systemic nor ocular disease. All 70 patients underwent a complete ophthalmic examination as well as choroidal thickness measurement using a high speed and high resolution SD-OCT device (Topcon 3D OCT-2000, Japan). There was no significant difference with respect to mean refractive error and intraocular pressure measurement between patients with PXS and controls (p = 0.237 and 0.433, respectively). The mean choroidal thickness was found as 206.6 ± 37.6 µm in the PXS group and 215.9 ± 47.3 µm in controls, respectively. The mean choroidal thickness was not significant between the PXS patients and the control cases (p = 0.362). Although PXS patients had lower mean choroidal thickness than controls, our results did not reach any statistical significance. PMID:25059402

  3. Evaluation of Retinal and Choroidal Thickness in Fuchs' Uveitis Syndrome

    PubMed Central

    Ozsutcu, Mustafa

    2016-01-01

    Purpose. We aimed to investigate retinal and choroidal thickness in the eyes of patients with Fuchs' uveitis syndrome (FUS). Methods. Fifteen patients with unilateral FUS and 20 healthy control subjects were enrolled. Spectral domain optical coherence tomography (Spectralis HRA+OCT, 870 nm; Heidelberg Engineering, Heidelberg, Germany) was used to obtain retinal and choroidal thickness measurements. The retinal nerve fiber layer (RNFL) thickness, macular thickness, and choroidal thickness of the eyes with FUS were compared with the unaffected eye and the eyes of healthy control subjects. Results. The mean choroidal thickness at fovea and at each point within the horizontal nasal and temporal quadrants at 500 μm intervals to a distance of 1500 µm from the foveal center was significantly thinner in the affected eye of FUS patients compared with the unaffected eye of FUS patients or the eyes of healthy control subjects. However, there were no significant differences in RNFL or macular thickness between groups. Conclusions. Affected eyes in patients with FUS tend to have thinner choroids as compared to eyes of unaffected fellow eyes and healthy individuals, which might be a result of the chronic inflammation associated with the disease. PMID:27579176

  4. [Effects of brovincamine fumarate on choroidal blood volume in rabbits].

    PubMed

    Tawara, A; Tanaka, T; Tsujioka, K; Sudo, Y; Ohnishi, Y

    1998-10-01

    We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits. PMID:9834607

  5. Bone Remodeling in Choroidal Osteoma Monitored by Fundus Photography and Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Kamalden, Tengku Ain; Lingam, Gopal; Sundar, Gangadhara

    2014-01-01

    Choroidal osteoma is a benign ossifying tumor of the choroid, consisting of mature bone tissue. It has been described to enlarge and evolve at varying rates over time. Here, we report and quantify the progression of a unilateral choroidal osteoma in a 7-year-old boy by fundus photography, and document tumor remodeling by spectral domain optical coherence tomography images. PMID:27175357

  6. Oxidized guanine lesions and hOgg1 activity in lung cancer.

    PubMed

    Mambo, Elizabeth; Chatterjee, Aditi; de Souza-Pinto, Nadja C; Mayard, Sabine; Hogue, Barbara A; Hoque, Mohammad O; Dizdaroglu, Miral; Bohr, Vilhelm A; Sidransky, David

    2005-06-30

    In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8-oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression (approximately 80% decrease) relative to normal cell lines. Liquid chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650 and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1 protein was associated with a decrease in mitochondrial DNA repair in response to oxidative damaging agents. These results provide evidence for defective incision of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell lines. These results may implicate 8-oxoG repair defects in certain lung cancers. PMID:15856018

  7. Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

    PubMed Central

    Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H.; Gothard, Katalin M.; Luh, Wen-Ming; Tootell, Roger B. H.; Murray, Elisabeth A.; Ungerleider, Leslie G.

    2012-01-01

    We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions—neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)—were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. PMID:23184972

  8. Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex.

    PubMed

    Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H; Gothard, Katalin M; Luh, Wen-Ming; Tootell, Roger B H; Murray, Elisabeth A; Ungerleider, Leslie G

    2012-12-26

    We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions--neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)--were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. PMID:23184972

  9. Iron oxide magnetic nanoparticles highlight early involvement of the choroid plexus in central nervous system inflammation

    PubMed Central

    Millward, Jason M.; Schnorr, Jörg; Taupitz, Matthias; Wagner, Susanne; Wuerfel, Jens T.; Infante-Duarte, Carmen

    2013-01-01

    Neuroinflammation during multiple sclerosis involves immune cell infiltration and disruption of the BBB (blood–brain barrier). Both processes can be visualized by MRI (magnetic resonance imaging), in multiple sclerosis patients and in the animal model EAE (experimental autoimmune encephalomyelitis). We previously showed that VSOPs (very small superparamagnetic iron oxide particles) reveal CNS (central nervous system) lesions in EAE which are not detectable by conventional contrast agents in MRI. We hypothesized that VSOP may help detect early, subtle inflammatory events that would otherwise remain imperceptible. To investigate the capacity of VSOP to reveal early events in CNS inflammation, we induced EAE in SJL mice using encephalitogenic T-cells, and administered VSOP prior to onset of clinical symptoms. In parallel, we administered VSOP to mice at peak disease, and to unmanipulated controls. We examined the distribution of VSOP in the CNS by MRI and histology. Prior to disease onset, in asymptomatic mice, VSOP accumulated in the choroid plexus and in spinal cord meninges in the absence of overt inflammation. However, VSOP was undetectable in the CNS of non-immunized control mice. At peak disease, VSOP was broadly distributed; we observed particles in perivascular inflammatory lesions with apparently preserved glia limitans. Moreover, at peak disease, VSOP was prominent in the choroid plexus and was seen in elongated endothelial structures, co-localized with phagocytes, and diffusely disseminated in the parenchyma, suggesting multiple entry mechanisms of VSOP into the CNS. Thus, using VSOP we were able to discriminate between inflammatory events occurring in established EAE and, importantly, we identified CNS alterations that appear to precede immune cell infiltration and clinical onset. PMID:23452162

  10. Regulation of neural stem cells by choroid plexus cells population.

    PubMed

    Roballo, Kelly C S; Gonçalves, Natalia J N; Pieri, Naira C G; Souza, Aline F; Andrade, André F C; Ambrósio, Carlos E

    2016-07-28

    The choroid plexus is a tissue on the central nervous system responsible for producing cerebrospinal fluid, maintaining homeostasis and neural stem cells support; though, all of its functions still unclear. This study aimed to demonstrate the niches of choroid plexus cells for a better understanding of the cell types and functions, using the porcine as the animal model. The collected material was analyzed by histology, immunohistochemistry, and cell culture. The cell culture was characterizated by immunocytochemistry and flow cytometry. Our results showed OCT-4, TUBIII, Nestin, CD45, CD73, CD90 positive expression and GFAP, CD105 negative expression, also methylene blue histological staining confirmed the presence of telocytes cells. We realized that the choroid plexus is a unique and incomparable tissue with different niches of cells as pluripotent, hematopoietic, neuronal progenitors and telocyte cells, which provide its complexity, differentiated functionality and responsibility on brain balance and neural stem cells regulation. PMID:27181512

  11. Chorioretinal temperature monitoring during transpupillary thermotherapy for choroidal neovascularisation

    PubMed Central

    Miura, S; Nishiwaki, H; Ieki, Y; Hirata, Y; Honda, Y; Sugino, Y; Okazaki, Y

    2005-01-01

    Aims: To investigate the difference in temperature rise between normal choroid and choroidal revascularisation (CNV) during transpupillary thermotherapy (TTT) and the relation between laser spot size and power in the rat fundus. Methods: A modified slit lamp, which was installed with two laser wavelengths (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT and temperature monitoring. Temperature rise during TTT was monitored by observing fluorescence released from thermosensitive liposomes encapsulating carboxyfluorescein. Two types of liposomes were prepared; their phase transition temperatures were 40°C and 46°C, respectively. Laser power settings required to observe fluorescence released from 46°C liposome in normal choroid or CNV were compared. Next, the power settings with 0.5 mm and 0.25 mm spot sizes were compared following administration of 40°C liposome or 46°C liposome. Results: The minimum power values when release from 46°C liposome was observed showed a significant difference in distribution of power values between normal choroid and CNV. CNV required significantly higher power than normal choroid. With 40°C liposome, the power was 9.7 (1.9) mW (mean (SD)) at a spot size of 0.25 mm, and 12.1 (1.6) mW at 0.5 mm, respectively. When using 46°C liposome, the power setting was 10.2 (1.2) mW at a spot size of 0.25 mm, and 14.6 (2.2) mW at 0.5 mm, respectively. Conclusions: CNV demonstrated varying heat conduction, compared with normal choroid. Laser power required to raise the temperature should not necessarily be doubled, even when the spot size is doubled. Close attention should be given to the selection of power settings when performing TTT for CNV. PMID:15774927

  12. Development of the choroid plexus and blood-CSF barrier

    PubMed Central

    Liddelow, Shane A.

    2015-01-01

    Well-known as one of the main sources of cerebrospinal fluid (CSF), the choroid plexuses have been, and still remain, a relatively understudied tissue in neuroscience. The choroid plexus and CSF (along with the blood-brain barrier proper) are recognized to provide a robust protective effort for the brain: a physical barrier to impede entrance of toxic metabolites to the brain; a “biochemical” barrier that facilitates removal of moieties that circumvent this physical barrier; and buoyant physical protection by CSF itself. In addition, the choroid plexus-CSF system has been shown to be integral for normal brain development, central nervous system (CNS) homeostasis, and repair after disease and trauma. It has been suggested to provide a stem-cell like repository for neuronal and astrocyte glial cell progenitors. By far, the most widely recognized choroid plexus role is as the site of the blood-CSF barrier, controller of the internal CNS microenvironment. Mechanisms involved combine structural diffusion restraint from tight junctions between plexus epithelial cells (physical barrier) and specific exchange mechanisms across the interface (enzymatic barrier). The current hypothesis states that early in development this interface is functional and more specific than in the adult, with differences historically termed as “immaturity” actually correctly reflecting developmental specialization. The advanced knowledge of the choroid plexus-CSF system proves itself imperative to understand a range of neurological diseases, from those caused by plexus or CSF drainage dysfunction (e.g., hydrocephalus) to more complicated late-stage diseases (e.g., Alzheimer's) and failure of CNS regeneration. This review will focus on choroid plexus development, outlining how early specializations may be exploited clinically. PMID:25784848

  13. Depth and activity of carious lesions as indicators for the regenerative potential of dental pulp after intervention.

    PubMed

    Bjørndal, Lars; Demant, Sune; Dabelsteen, Sally

    2014-04-01

    Studies on dental regeneration involving interventions for pulp therapy such as regeneration and revascularization procedures are promising for the injured tooth; however, a complete replication of the original pulp tissue does not seem to take place. In cases in which we wish to preserve or maintain parts of the pulp during treatment, it is apparent that the effectiveness of healing or biological regeneration is dependent on the degree of inflammation of the pulp tissue. Thus, the control or prevention of a pulp infection is still a major issue for the clinicians. Data indicate that the typical reason for performing endodontic treatment is deep caries. The biological concept of vital pulp therapy associated with deep caries takes the treatment and evaluation of the unexposed as well as the exposed pulp into account. Interestingly, the clinical diagnosis is typically the same. Deep caries with reversible pulpitis may receive differing treatments such as excavation procedures aiming to avoid pulp exposure or more pulp invasive treatments such as pulp capping or pulpotomy. This should not be the case. Consequently, huge treatment variation is noted among clinicians based on the same caries diagnosis. Which treatment should be selected? High-quality trials are needed, and it is important to obtain information on the actual lesion depth and an estimate of the lesion activity before treatment. These may be basic indicators for the regenerative potential of dental pulp. Recent clinical trials dealing with the treatment of deep caries lesion are discussed, including pulp invasive and noninvasive concepts, to attempt to solve the task of getting the best clinical outcome for adult patients. PMID:24698699

  14. Development and functions of the choroid plexus–cerebrospinal fluid system

    PubMed Central

    Lun, Melody P.; Monuki, Edwin S.; Lehtinen, Maria K.

    2015-01-01

    The choroid plexus (ChP) is the principal source of cerebrospinal fluid (CSF), which has accepted roles as a fluid cushion and a sink for nervous system waste in vertebrates. Various animal models have provided insight into how the ChP–CSF system develops and matures. In addition, recent studies have uncovered new, active roles for this dynamic system in the regulation of neural stem cells, critical periods and the overall health of the nervous system. Together, these findings have brought about a paradigm shift in our understanding of brain development and health, and have stimulated new initiatives for the treatment of neurological disease. PMID:26174708

  15. A stereological study of the ependyma of the mouse spinal cord. With a comparative note on the choroid plexus ependyma.

    PubMed Central

    Bjugn, R; Bøe, R; Haugland, H K

    1989-01-01

    Applying different stereological techniques, the total ependymal volume in the spinal cord of mice was estimated to be 83 x 10(6) microns cubed, the number of cells to be 163,000 and the mean ependymal cell volume to be 510 microns cubed. Compared to choroid plexus cells in the third ventricle, the ependymal cells in the spinal cord contained a smaller mitochondrial volume (9.8% versus 4.6% of cell volume) and less rough endoplasmic reticulum (2.1% versus 0.4%). These findings indicate that the metabolic activity of the ependyma in the spinal cord is lower than that in the choroid plexus. Compared to liver and exocrine pancreatic cells, ependymal cells in both locations must be considered to have a rather low metabolic activity. PMID:2621136

  16. Inhibition of RACK1 ameliorates choroidal neovascularization formation in vitro and in vivo.

    PubMed

    Liu, Xiaojuan; Zhu, Manhui; Yang, Xiaowei; Wang, Ying; Qin, Bai; Cui, Chen; Chen, Hui; Sang, Aimin

    2016-06-01

    Choroidal neovascularization (CNV) occurs as a result of age-related macular degeneration (AMD) and causes severe vision loss among elderly patients. The receptor for activated C-kinase 1 (RACK1) serves as a scaffold protein which is recently found to promote angiogenesis. However, the impact of RACK1 on the vascular endothelial growth factor (VEGF) expression in endothelial cells and subsequent choroidal angiogenesis formation remains to be elucidated. In this study, we found that RACK1 and VEGF expression increased, and reached the peak at 7d in mouse CNV model by laser application. Furthermore, on RPE/choroid cryosections, RACK1 co-localized with CD31, suggesting that RACK1 was expressed in endothelial cells. In vitro, RF/6A cell hypoxia model showed that RACK1 expression was up-regulated in parallel with hypoxia-induced factor 1 (HIF-1α) and VEGF expression, reaching the peak at 6h. Silencing of RACK1 suppressed the invasion and tube formation activity of RF/6A cells in ARPE-19 and RF/6A co-culture system, possibly through VEGF signal pathway. Overexpression of RACK1 showed the opposite effect. Intravitreal injection of anti-RACK1 monoclonal antibody predominantly decreased RACK1 and VEGF expression in mouse laser-induced CNV model. Meanwhile, anti-RACK1 monoclonal antibody intravitreal injection also decreased incidence of CNV and leakage area. These data indicated that RACK1 promoted CNV formation via VEGF pathway. Additionally, anti-RACK1 monoclonal antibody significantly decreased CNV in mouse model and may have therapeutic potential in human CNV. PMID:27112838

  17. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.; Wakefield, Matthew J.; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A.

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2–98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  18. Influx mechanisms in the embryonic and adult rat choroid plexus: a transcriptome study.

    PubMed

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D; Wakefield, Matthew J; Lindsay, Helen; Stratzielle, Nathalie; Ghersi-Egea, Jean-Francois; Liddelow, Shane A

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and adult with additional data obtained at intermediate ages from microarray analysis. The largest represented functional group in the embryo was amino acid transporters (twelve) with expression levels 2-98 times greater than in the adult. In contrast, in the adult only six amino acid transporters were up-regulated compared to the embryo and at more modest enrichment levels (<5-fold enrichment above E15). In E15 plexus five glucose transporters, in particular Glut-1, and only one monocarboxylate transporter were enriched compared to the adult, whereas only two glucose transporters but six monocarboxylate transporters in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing brain with higher amino acid transport activity reported previously. Data for divalent metal transporters are also considered. Immunohistochemistry of several transporters (e.g., Slc16a10, a thyroid hormone transporter) gene products was carried out to confirm translational activity and to define cellular distribution of the proteins. Overall the results show that there is substantial expression of numerous influx transporters in the embryonic choroid plexus, many at higher levels than in the adult. This, together with immunohistochemical evidence and data from published physiological transport studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients. PMID:25972776

  19. Suggested management guidelines for participation in collision activities with congenital, developmental, or postinjury lesions involving the cervical spine.

    PubMed

    Torg, J S; Ramsey-Emrhein, J A

    1997-07-01

    Many conditions involving the cervical spine in the athlete require a management decision. The purpose of this paper is to present appropriate guidelines for return to collision activities in those with congenital, developmental, or post-injury lesions. Information compiled from over 1200 cervical spine lesions documented by the National Football Head & Neck Injury Registry, an extensive literature review, as well as an understanding of injury mechanisms have resulted in reasonable management guidelines. Each of the congenital, developmental, and post-traumatic conditions presented are determined to present either no contraindication, relative contraindication, or an absolute contraindication on the basis of a variety of parameters. Conditions included in the discussion are: odontoid anomalies; spina bifida occulta; atlanto-occipital fusion; Klipple-Feil anomalies; cervical canal stenosis; spear tackler's spine; and traumatic conditions of the upper, middle, and lower cervical spine, including ligamentous injuries and fractures, intervertebral disc injuries, and post-cervical spine fusion. Emphasized is the fact that the proposed guidelines should be used in the decision-making process in conjuction with other factors such as the age, experience, ability of the individual, level of participation, position played, as well as the attitude and desires of the athlete and his parents after an informed discussion of the problem with particular regard to potential risk. PMID:9247923

  20. Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic

    PubMed Central

    2005-01-01

    Objective To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. Methods Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye (“study eye”). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. Results Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89–1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n=92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08–2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month

  1. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis.

    PubMed

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  2. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis

    PubMed Central

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  3. The MEG topography and the source model of abnormal neural activities associated with brain lesions

    SciTech Connect

    Ueno, S.; Iramina, K.; Ozaki, H.; Harada, K.

    1986-09-01

    A source model is proposed to simulate spatial distributions of abnormal MEG and EEG activities generated by abnormal neural activities such as the delta activity associated with brain tumors. Brain tumor itself is electrically silent and the spherical shell around the tumor might generate abnormal neural activities. The sources of these neural activities are represented by combinations of multiple current dipoles. The head is assumed to be a spherical volume conductor. Electrical potentials and magnetic fields over the surface of the spheres are calculated. The computer simulation shows that the MEG topography and EEG topography vary variously with combinations of location and orientation of the dipoles. In a special case, however, that the dipoles orient in the same direction or orient radially, the spatial patterns of the MEGs and EEGs generated by numerous dipoles are analogous to those generated by single dipoles.

  4. Subependymal giant cell astrocytoma: a lesion with activated mTOR pathway and constant expression of glutamine synthetase.

    PubMed

    Buccoliero, Anna Maria; Caporalini, Chiara; Giordano, Flavio; Mussa, Federico; Scagnet, Mirko; Moscardi, Selene; Baroni, Gianna; Genitori, Lorenzo; Taddei, Gian Luigi

    2016-01-01

    Subependymal giant-cell astrocytoma (SEGA) is a rare tumor associated with tuberous sclerosis complex (TSC). TSC mainly involves the central nervous system (CNS) where SEGA, subependymal nodules, and cortical tubers may be present. First studies suggested the astrocytic nature of SEGA while successive studies demonstrated the mixed glio-neuronal nature. There are similarities between TSC-associated CNS lesions and type IIb focal cortical dysplasia (FCD). In all these pathologies, mammalian target of rapamycin (mTOR) pathway activation has been demonstrated. Recent data evidenced that balloon cells in FCD IIb express glutamine synthetase (GS). GS is involved in the clearance of glutamate. Cells expressing GS might exert an antiepileptic role. We evaluated by immunohistochemistry the glial fibrillary acidic protein (GFAP), neurofilaments (NF), and GS expression and the mTOR status (mTOR and phosphorylated ribosomal protein S6) in 16 SEGAs and 2 cortical tubers. Our purpose was to emphasize the mixed nature of SEGA and to further investigate the similarities between TSC-related CNS lesions (in particular SEGA) and FCD IIb. We confirm the glio-neuronal nature and the common activation of the mTOR pathway in SEGAs. In addition, we report for the first time that these tumors, analogously to FCD IIb, commonly express GS. Notably, the expression of mTOR, phosphorylated ribosomal protein S6, and GS was restricted to gemistocytic-like GFAP-negative cells. GS expression and mTOR pathway activation were also documented in cortical tubers. Further studies are necessary to understand the significance of GS expression in SEGAs as well as in cortical tubers. PMID:27390104

  5. VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis

    PubMed Central

    Yi, Jin-Ping; Wu, Yu-Zhang; Yu, Nan; Yu, Zhi-Wu; Xie, Fu-Yuan; Yuan, Quan

    2016-01-01

    Background Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). Material/Methods Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. Results The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). Conclusions Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA. PMID:26825024

  6. Involvement of nigral oxytocin in locomotor activity: A behavioral, immunohistochemical and lesion study in male rats.

    PubMed

    Angioni, Laura; Cocco, Cristina; Ferri, Gian-Luca; Argiolas, Antonio; Melis, Maria Rosaria; Sanna, Fabrizio

    2016-07-01

    Oxytocin is involved in the control of different behaviors, from sexual behavior and food consumption to empathy, social and affective behaviors. An imbalance of central oxytocinergic neurotransmission has been also associated with different mental pathologies, from depression, anxiety and anorexia/bulimia to schizophrenia, autism and drug dependence. This study shows that oxytocin may also play a role in the control of locomotor activity. Accordingly, intraperitoneal oxytocin (0.5-2000μg/kg) reduced locomotor activity of adult male rats. This effect was abolished by d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist, given into the lateral ventricles at the dose of 2μg/rat, which was ineffective on locomotor activity. Oxytocin (50-200ng/site) also reduced and d(CH2)5Tyr(Me)(2)-Orn(8)-vasotocin (2μg/site) increased locomotor activity when injected bilaterally into the substantia nigra, a key area in the control of locomotor activity. Conversely, the destruction of nigral neurons bearing oxytocin receptors by the recently characterized neurotoxin oxytocin-saporin injected into the substantia nigra, increased basal locomotor activity. Since oxytocin-saporin injected into the substantia nigra caused a marked reduction of neurons immunoreactive for tyrosine hydroxylase (e.g., nigrostriatal dopaminergic neurons) and for vesicular glutamate transporters VGluT1, VGluT2 and VGluT3 (e.g., glutamatergic neurons), but not for glutamic acid decarboxylase (e.g., GABAergic neurons), together these findings suggest that oxytocin influences locomotor activity by acting on receptors localized presynaptically in nigral glutamatergic nerve terminals (which control the activity of nigral GABAergic efferent neurons projecting to brain stem nuclei controlling locomotor activity), rather than on receptors localized in the cell bodies/dendrites of nigrostriatal dopaminergic neurons. PMID:27189764

  7. The neural milieu of the developing choroid plexus: neural stem cells, neurons and innervation.

    PubMed

    Prasongchean, Weerapong; Vernay, Bertrand; Asgarian, Zeinab; Jannatul, Nahin; Ferretti, Patrizia

    2015-01-01

    The choroid plexus produces cerebrospinal fluid and plays an important role in brain homeostasis both pre and postnatally. In vitro studies have suggested that cells from adult choroid plexus have stem/progenitor cell-like properties. Our initial aim was to investigate whether such a cell population is present in vivo during development of the choroid plexus, focusing mainly on the chick choroid plexus. Cells expressing neural markers were indeed present in the choroid plexus of chick and also those of rodent and human embryos, both within their epithelium and mesenchyme. ß3-tubulin-positive cells with neuronal morphology could be detected as early as at E8 in chick choroid plexus and their morphological complexity increased with development. Whole mount immunochemistry demonstrated the presence of neurons throughout choroid plexus development and they appeared to be mainly catecholaminergic, as indicated by tyrosine-hydroxylase reactivity. The presence of cells co-labeling for BrdU and the neuroblast marker, doublecortin, in organotypic choroid plexus cultures supported the hypothesis that neurogenesis can occur from neural precursors within the developing choroid plexus. Furthermore, we found that extrinsic innervation is present in the developing choroid plexus, unlike previously suggested. Altogether, our data are consistent with the presence of neural progenitors within the choroid plexus, suggest that at least some of the choroid plexus neurons are born locally, and show for the first time that choroid plexus innervation occurs prenatally. Hence, we propose the existence of a complex neural regulatory network within the developing choroid plexus that may play a crucial role in modulating its function during development as well as throughout life. PMID:25873856

  8. Silent polypoidal choroidal vasculopathy in a patient with angioid streaks.

    PubMed

    Cebeci, Zafer; Bayraktar, Serife; Oray, Merih; Kir, Nur

    2016-01-01

    We present a case of silent polypoidal choroidal vasculopathy (PCV) in a patient with angioid streaks. PCV was detected during a routine ophthalmic examination and confirmed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. After 2 years of follow-up, the PCV remained silent without any complications. We report this rare coexistence and review literature on this topic. PMID:27463636

  9. Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

    PubMed

    Jarjisian, Stephan G; Butler, Matthew P; Paul, Matthew J; Place, Ned J; Prendergast, Brian J; Kriegsfeld, Lance J; Zucker, Irving

    2015-02-01

    The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs. PMID:25512303

  10. [Clinical significance of telomerase activity in precancerous lesion of the liver (adenomatous hyperplasia)].

    PubMed

    Nishimoto, A; Miura, N; Oshimura, M

    1998-05-01

    To understand the role of telomere dynamics in hepatocellular carcinogenesis, we examined the lengths of terminal restriction fragments (TRFs) in hepatocellular carcinoma (HCC) and surrounding tissues with chronic active hepatitis (CAH), liver cirrhosis (LC) and atypical adenomatous hyperplasia (AAH). The peak TRFs in all HCCs were significantly shorter than those of the surrounding tissues (CAH, LC). TRF in AAH was shortened and similar to that of HCC. Telomerase was examined in CAH, LC, AH, and HCC, and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AH was similar to that of HCC. Thus, the progressive shortening of telomere and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9613131

  11. Kir7.1 immunoreactivity in canine choroid plexus tumors.

    PubMed

    Choi, Eun Ju; Sloma, Erica A; Miller, Andrew D

    2016-07-01

    Choroid plexus neoplasms are uncommon brain tumors in dogs. Choroid plexus carcinomas often spread diffusely throughout the ventricular system and subarachnoid space and, in aggressive forms, can mimic histologic patterns of other carcinomas, including being embedded in a desmoplastic reaction. Although choroid plexus tumors (CPTs) heterogeneously express pan-cytokeratin, little is known about other markers to identify choroid plexus and their associated tumors. Kir7.1, an inward-rectifier potassium channel, is reported to have high diagnostic utility in human neuropathology to distinguish CPTs from other primary brain tumors and cerebral metastases. To determine Kir7.1 expression in the dog brain, we analyzed the immunoreactivity of Kir7.1 in normal brain, gliomas, ependymomas, CPTs, meningiomas, and carcinomas. In normal brain tissue, the immunostaining was restricted to the choroid plexus where there was robust membrane immunoreactivity along the apical border of the cells with less intense cytoplasmic staining. Similar strong immunoreactivity was detected in 12 of 12 CPTs, whereas 5 of 5 gliomas, 4 of 5 ependymomas, 5 of 5 meningiomas, and 5 of 6 carcinomas had no immunoreactivity. One ependymoma and 1 nasal carcinoma with squamous metaplasia were up to 75% immunopositive, with moderate cytoplasmic and membranous immunoreactivity, but lacking the robust apical immunoreactivity pattern. Analysis for immunoreactivity in a tissue microarray failed to yield any other locations in which immunoreactivity was detected. These results, including the distinctive pattern of immunostaining in CPTs, suggest that Kir7.1 is an excellent marker for CPTs in the dog. PMID:27216721

  12. Choroidal Blood Flow Change in Eyes with High Myopia

    PubMed Central

    Yang, Young Seong

    2015-01-01

    Purpose To evaluate choroidal blood flow changes in eyes with high myopia according to the pulsatile components of ocular blood flow analysis. Methods A total of 104 subjects (52 males and 52 females) were included in this study. One eye of each participant was randomly selected and assigned to one of four refractive groups, designated as, hyperopes (n = 20; refractive error, ≥+1.00 diopter [D]), emmetropes (n = 28; refractive error, ±0.75 D), lower myopes (n = 33; refractive error, -1.00 to -4.75 D), and high myopes (n = 23; refractive error, ≤-5.00 D). Components of pulse amplitude (OBFa), pulse volume (OBFv), pulse rate (OBFr), and pulsatile ocular blood flow (POBF) were analyzed using a blood flow analyzer. Intraocular pressure and axial length were measured. Results Pulsatile components of OBFa, OBFv, and POBF showed positive correlations with refractive error and showed negative correlations with axial length (r = 0.729, r = 0.772, r = 0.781, respectively, all p < 0.001; r = -0.727, r = -0.762, r = -0.771, respectively, all p < 0.001). The correlations of refractive error and axial length with OBFr were irrelevant (r = -0.157, p = 0.113; r = 0.123, p = 0.213). High myopes showed significantly lower OBFa, OBFv, and POBF than the other groups (all p < 0.001). Conclusions Axial length changes in high myopes potentially influence choroidal blood flow, assuming the changes are caused by narrowing of the choroidal vessel diameter and increasing rigidity of the choroidal vessel wall. These finding explains the influence of axial length on OBFa, OBFv, and POBF, but not on OBFr. Thus, changes in axial length and the possible influence of these changes on the physical properties of choroidal vessels is the mechanism believed to be responsible for putting high myopes at risk for ocular vascular diseases. PMID:26457036

  13. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren

    PubMed Central

    Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8–16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia. PMID:27537606

  14. Choroidal thickness in pregnant women: a cross-sectional study

    PubMed Central

    Liu, Ru; Kuang, Guo-Ping; Luo, Di-Xian; Lu, Xiao-He

    2016-01-01

    AIM To investigate choroidal thickness in pregnant women and compare the measurements with those of normal nonpregnant women. METHODS Using enhanced depth imaging optical coherence tomography (EDI-OCT), choroidal thickness was measured at the fovea and at 1 mm and 3 mm superior, inferior, temporal, and nasal to the fovea in both healthy pregnant women and nonpregnant women. Pearson correlation analysis was performed to evaluate the relationships between subfoveal choroidal thickness (SFCT) and the demographic and ocular parameters. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects model when Meta-analyses were conducted. RESULTS Comparison of choroidal thickness between the groups showed that it was significantly greater in healthy pregnant women's eyes than in normal nonpregnant women's eyes at all locations except at 3 mm superior and 3 mm temporal from the fovea (P<0.05). The mean SFCT was 344.13±50.94 µm in healthy pregnant women's eyes and 315.03±60.57 µm in normal nonpregnant women's eyes, with a statistically significant difference (P=0.008). Pearson correlation analysis showed that age and axial length were significantly related to SFCT in healthy pregnant women, normal nonpregnant women, and all subjects. The results of our cross-sectional study were consistent with the results of the further Meta-analysis, with a pooled weighted mean difference (WMD) of 33.66 µm (95% CI: 26.16 to 41.15) for SFCT. CONCLUSION Our results, along with the comprehensive Meta-analysis, suggest that choroidal thickness in healthy pregnant women is greater than that in normal nonpregnant women. PMID:27588276

  15. Episcleral plaque thermoradiotherapy in patients with choroidal melanoma.

    PubMed

    Petrovich, Z; Astrahan, M A; Luxton, G; Green, R; Langholz, B; Liggett, P

    1992-01-01

    From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma. PMID:1612961

  16. Distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions

    PubMed Central

    Serrano, Carmen; Lyahyai, Jaber; Bolea, Rosa; Varona, Luis; Monleón, Eva; Badiola, Juan J.; Zaragoza, Pilar; Martín-Burriel, Inmaculada

    2009-01-01

    Neurodegeneration and gliosis are the main neuropathological features of prion diseases. However, the molecular mechanisms involved in these processes remain unclear. Several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. Here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. Expression changes obtained by real-time RT-PCR were also compared with the extent of classical scrapie lesions, such as prion deposition, neuronal vacuolisation, spongiosis, and astrogliosis as well as with the activation of caspase-3, using a stepwise regression. The results suggest that the factors assessed participate in apoptotic or inflammatory functions, depending on the affected area. The mitochondrial apoptosis pathway was associated with prion deposition in the prefrontal cortex (the less affected area), and with activation of caspase-3-mediated cell death via over-expression of BAK. In addition to its known association with astroglial activation, the extrinsic apoptosis pathway was also related to cell death and neuronal vacuolisation. PMID:19401142

  17. Bobble-head doll syndrome and drop attacks in a child with a cystic choroid plexus papilloma of the third ventricle. Case report.

    PubMed

    Pollack, I F; Schor, N F; Martinez, A J; Towbin, R

    1995-10-01

    The authors report an unusual case of a 2-year-old boy with a 3-month history of episodic rightward anterolateral head tilt and large-amplitude positional anteroposterior head bobbing reminiscent of bobble-head doll syndrome. This child experienced a sudden onset of drop attacks and then, within several hours, deep coma. The causative lesion was a contrast-enhancing, partially cystic third ventricular mass, which ultimately obstructed the aqueduct, producing profound obstructive hydrocephalus. An emergency ventriculostomy and endoscopic fenestration of the septum pellucidum was performed. Four days later, the tumor was completely resected by a transcallosal-transforaminal approach. The lesion was freely mobile within the third ventricle and contained a large cyst within its posterior pole; following drainage of the cyst, the lesion was easily delivered through the foramen of Monro. The histopathological diagnosis was choroid plexus papilloma. The child's neurological deficits, head tilt, and head bobbing resolved immediately after operation. To the best of the authors' knowledge, this represents the first well-documented report of bobble-head doll syndrome and drop attacks secondary to a choroid plexus papilloma. The highly mobile nature of the cystic lesion presumably led to its intermittent impaction within the foramen of Monro and/or proximal aqueduct; this produced the intermittent head tilt and bobble-head symptoms and, ultimately, resulted in acute obstruction of the aqueduct, causing the child's precipitous neurological decline. PMID:7674025

  18. A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

    PubMed

    Gomez, A; Bernardoni, N; Rieman, J; Dusick, A; Hartshorn, R; Read, D H; Socha, M T; Cook, N B; Döpfer, D

    2014-10-01

    A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD

  19. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    NASA Astrophysics Data System (ADS)

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-02-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

  20. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    PubMed Central

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-01-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases. PMID:26868048

  1. Targetable Kinase-Activating Lesions in Ph-like Acute Lymphoblastic Leukemia

    PubMed Central

    Roberts, K.G.; Li, Y.; Payne-Turner, D.; Harvey, R.C.; Yang, Y.-L.; Pei, D.; McCastlain, K.; Ding, L.; Lu, C.; Song, G.; Ma, J.; Becksfort, J.; Rusch, M.; Chen, S.-C.; Easton, J.; Cheng, J.; Boggs, K.; Santiago-Morales, N.; Iacobucci, I.; Fulton, R.S.; Wen, J.; Valentine, M.; Cheng, C.; Paugh, S.W.; Devidas, M.; Chen, I-M.; Reshmi, S.; Smith, A.; Hedlund, E.; Gupta, P.; Nagahawatte, P.; Wu, G.; Chen, X.; Yergeau, D.; Vadodaria, B.; Mulder, H.; Winick, N.J.; Larsen, E.C.; Carroll, W.L.; Heerema, N.A.; Carroll, A.J.; Grayson, G.; Tasian, S.K.; Moore, A.S.; Keller, F.; Frei-Jones, M.; Whitlock, J.A.; Raetz, E.A.; White, D.L.; Hughes, T.P.; Auvil, J.M. Guidry; Smith, M.A.; Marcucci, G.; Bloomfield, C.D.; Mrózek, K.; Kohlschmidt, J.; Stock, W.; Kornblau, S.M.; Konopleva, M.; Paietta, E.; Pui, C.-H.; Jeha, S.; Relling, M.V.; Evans, W.E.; Gerhard, D.S.; Gastier-Foster, J.M.; Mardis, E.; Wilson, R.K.; Loh, M.L.; Downing, J.R.; Hunger, S.P.; Willman, C.L.; Zhang, J.; Mullighan, C.G.

    2014-01-01

    BACKGROUND Philadelphia chromosome–like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR–ABL1–positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. METHODS We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL. We examined the functional effects of fusion proteins and the efficacy of tyrosine kinase inhibitors in mouse pre-B cells and xenografts of human Ph-like ALL. RESULTS Ph-like ALL increased in frequency from 10% among children with standard-risk ALL to 27% among young adults with ALL and was associated with a poor outcome. Kinase-activating alterations were identified in 91% of patients with Ph-like ALL; rearrangements involving ABL1, ABL2, CRLF2, CSF1R, EPOR, JAK2, NTRK3, PDGFRB, PTK2B, TSLP, or TYK2 and sequence mutations involving FLT3, IL7R, or SH2B3 were most common. Expression of ABL1, ABL2, CSF1R, JAK2, and PDGFRB fusions resulted in cytokine-independent proliferation and activation of phosphorylated STAT5. Cell lines and human leukemic cells expressing ABL1, ABL2, CSF1R, and PDGFRB fusions were sensitive in vitro to dasatinib, EPOR and JAK2 rearrangements were sensitive to ruxolitinib, and the ETV6–NTRK3 fusion was sensitive to crizotinib. CONCLUSIONS Ph-like ALL was found to be characterized by a range of genomic alterations that activate a limited number of signaling pathways, all of which may be amenable to inhibition with approved tyrosine kinase inhibitors. Trials identifying Ph-like ALL are needed to assess whether adding tyrosine kinase inhibitors to current therapy will improve the survival of patients with this type of leukemia. (Funded by the American Lebanese Syrian Associated Charities and

  2. [Gastric myoelectric activity disturbance in patients with traumatic lesions of the brain stem].

    PubMed

    Thor, Piotr J; Madroszkiewicz, Dorota; Moskała, Marek; Madroszkiewicz, Ewa; Gościński, Igor

    2003-01-01

    The aim of the study was to evaluate effects of cranio-cerebral trauma on gastric myoelectric activity. Twenty four patients hospitalized in the Department of Neurotraumatology, Collegium Medicum of the Jagiellonian University were compared with a control group of 16 healthy volunteers matched for gender and age. Their gastric myoelectric activity was measured using standard cutaneous electrodes with Synectics, a Swedish system of data storage and analysis. Results of the study were analyzed at the Department of Pathophysiology, Collegium Medicum, Jagiellonian University. In the electrogastrography (EGG) recording of the control group the proportions of time with bradygastria (0.5-2 cpm), normogastria (2-4 cpm) and tachygastria (4-10 cpm) were 11.6 +/- 8%, 86.2 +/- 9% and 2.16 +/- 1.5% respectively. The signal amplitude was 181 +/- 11.5 microV2. In patients with a severe head injury followed by intracranial hypertension III degree and cerebral coma (the Glasgow Coma Scale score 4-7 points), the proportion of bradygastria in the total recording time amounted to 46.5 +/- 8%. In these patients also the signal amplitude was found to increase up to 766 microV2 (p = 0.0007). Our results indicate that in patients comatose due to a posttraumatic brainstem injury, the function of the brain-gut link is altered. There is a severe disorder of the upper gut motility, associated with gastric dysrhythmia--bradygastria resulting from an increased cholinergic output. This leads to intestinal feeding intolerance. PMID:15174250

  3. Malignant uveal melanoma and similar lesions studied by computed tomography

    SciTech Connect

    Mafee, M.F.; Peyman, G.A.; McKusick, M.A.

    1985-08-01

    Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, the authors noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability as the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.

  4. Efficacy of sealing proximal early active lesions: an 18-month clinical study evaluated by conventional and subtraction radiography.

    PubMed

    Martignon, S; Ekstrand, K R; Ellwood, R

    2006-01-01

    This study assessed the efficacy of sealing proximal lesions on adult patients using a split-mouth design. Eighty-two 15- to 39-year-olds from the Dental Faculties in Copenhagen and Bogotá participated, each having 2 or more proximal lesions in the following radiographic stages: (1) lesion restricted to the outer half of enamel; (2) lesion from the inner half of enamel including the enamel dentine junction, and (3) lesion restricted to the outer third of dentine. Standardized geometrically aligned baseline and follow-up radiographs were obtained. One randomly selected lesion (test) in each patient was sealed with 1 of 2 resins. The patients were instructed to floss all the proximal lesions 3 times per week. The baseline to 18 months difference in caries lesion progression status was assessed using 3 methods: (1) radiographs were independently assessed visually; (2) radiographs were read in pairs, and (3) using subtraction radiography of digitized images. A total of 72 subjects finished the study (12.2% dropout). The compliance concerning flossing was poor (15%). For the repeated examinations kappa was 0.84 for the visual examination, 0.44 for the paired readings and 0.84 for the subtraction examination. Two test lesions and 1 control lesion were restored. For the independent radiograph assessment method 10 and 26% progressed in the test and control group, respectively (p > 0.05); with the paired radiograph method the corresponding data were 22% in the test and 47% in the control groups (p < 0.01). By subtraction radiography 44% of the test group and 84% of the control were judged to have progressed (p < 0.001). The sealing technique was superior to instructing patients to floss, and subtraction radiography appeared to be the most sensitive method for assessing lesion progression. PMID:16946605

  5. Therapeutic Effect of Oral Bisphosphonates on Choroidal Neovascularization in the Human Eye

    PubMed Central

    Honda, Shigeru; Nagai, Takayuki; Kondo, Naoshi; Fukuda, Masahide; Kusuhara, Sentaro; Tsukahara, Yasutomo; Negi, Akira

    2010-01-01

    Purpose. Choroidal neovascularization (CNV) is often associated with age-related macular degeneration (AMD) and pathological myopia (PM). Bisphosphonates, the drug of choice to treat osteoporosis, have been recently reported to have anti-angiogenic effects. The purpose of this study is to investigate the therapeutic effects of oral bisphosphonates for CNV in humans. Methods. Thirty-six consecutive cases with CNV due to AMD or PM who declined anti-VEGF therapy were recruited. The patients were prescribed 5 mg of oral alendronates daily for 6 months. The best-corrected visual-acuity (BCVA), the lesion size in fundus photographs and fluorescein angiography, foveal thickness and total macular volume in optical coherence tomography were compared between pre- and post-treatment. Results. The mean BCVA of the patients was significantly improved after a months with the treatment in the AMD group. In the PM group, the mean BCVA was maintained up to 6 months with the treatment. The mean lesion size was significantly decreased by 3 months in both groups. The averages of foveal thickness and total macular volume were significantly reduced after 1 month of treatment in the AMD group.Conclusions. Oral bisphosphonate should be further investigated as a possible therapeutic and preventive drug for CNV due to AMD and PM. PMID:20706646

  6. A non membrane-targeted human soluble CD59 attenuates choroidal neovascularization in a model of age related macular degeneration.

    PubMed

    Cashman, Siobhan M; Ramo, Kasmir; Kumar-Singh, Rajendra

    2011-01-01

    Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD. PMID:21552568

  7. Metabolic Syndrome Triggered by High-Fructose Diet Favors Choroidal Neovascularization and Impairs Retinal Light Sensitivity in the Rat

    PubMed Central

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M.; Creuzot-Garcher, Catherine P.; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model. PMID:25380250

  8. Segmentation of the macular choroid in OCT images acquired at 830nm and 1060nm

    NASA Astrophysics Data System (ADS)

    Lee, Sieun; Beg, Mirza F.; Sarunic, Marinko V.

    2013-06-01

    Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.

  9. A missense variant in FGD6 confers increased risk of polypoidal choroidal vasculopathy.

    PubMed

    Huang, Lulin; Zhang, Houbin; Cheng, Ching-Yu; Wen, Feng; Tam, Pancy O S; Zhao, Peiquan; Chen, Haoyu; Li, Zheng; Chen, Lijia; Tai, Zhengfu; Yamashiro, Kenji; Deng, Shaoping; Zhu, Xianjun; Chen, Weiqi; Cai, Li; Lu, Fang; Li, Yuanfeng; Cheung, Chui-Ming G; Shi, Yi; Miyake, Masahiro; Lin, Yin; Gong, Bo; Liu, Xiaoqi; Sim, Kar-Seng; Yang, Jiyun; Mori, Keisuke; Zhang, Xiongzhe; Cackett, Peter D; Tsujikawa, Motokazu; Nishida, Kohji; Hao, Fang; Ma, Shi; Lin, He; Cheng, Jing; Fei, Ping; Lai, Timothy Y Y; Tang, Sibo; Laude, Augustinus; Inoue, Satoshi; Yeo, Ian Y; Sakurada, Yoichi; Zhou, Yu; Iijima, Hiroyuki; Honda, Shigeru; Lei, Chuntao; Zhang, Lin; Zheng, Hong; Jiang, Dan; Zhu, Xiong; Wong, Tien-Ying; Khor, Chiea-Chuen; Pang, Chi-Pui; Yoshimura, Nagahisa; Yang, Zhenglin

    2016-06-01

    Polypoidal choroidal vasculopathy (PCV), a subtype of 'wet' age-related macular degeneration (AMD), constitutes up to 55% of cases of wet AMD in Asian patients. In contrast to the choroidal neovascularization (CNV) subtype, the genetic risk factors for PCV are relatively unknown. Exome sequencing analysis of a Han Chinese cohort followed by replication in four independent cohorts identified a rare c.986A>G (p.Lys329Arg) variant in the FGD6 gene as significantly associated with PCV (P = 2.19 × 10(-16), odds ratio (OR) = 2.12) but not with CNV (P = 0.26, OR = 1.13). The intracellular localization of FGD6-Arg329 is distinct from that of FGD6-Lys329. In vitro, FGD6 could regulate proangiogenic activity, and oxidized phospholipids increased expression of FGD6. FGD6-Arg329 promoted more abnormal vessel development in the mouse retina than FGD6-Lys329. Collectively, our data suggest that oxidized phospholipids and FGD6-Arg329 might act synergistically to increase susceptibility to PCV. PMID:27089177

  10. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  11. Human cerebrospinal fluid central memory CD4+ T cells: Evidence for trafficking through choroid plexus and meninges via P-selectin

    PubMed Central

    Kivisäkk, Pia; Mahad, Don J.; Callahan, Melissa K.; Trebst, Corinna; Tucky, Barbara; Wei, Tao; Wu, Lijun; Baekkevold, Espen S.; Lassmann, Hans; Staugaitis, Susan M.; Campbell, James J.; Ransohoff, Richard M.

    2003-01-01

    Cerebrospinal fluid (CSF) from healthy individuals contains between 1,000 and 3,000 leukocytes per ml. Little is known about trafficking patterns of leukocytes between the systemic circulation and the noninflamed CNS. In the current study, we characterized the surface phenotype of CSF cells and defined the expression of selected adhesion molecules on vasculature in the choroid plexus, the subarachnoid space surrounding the cerebral cortex, and the cerebral parenchyma. Using multicolor flow cytometry, we found that CSF cells predominantly consisted of CD4+/CD45RA-/CD27+/CD69+-activated central memory T cells expressing high levels of CCR7 and L-selectin. CD3+ T cells were present in the choroid plexus stroma in autopsy CNS tissue sections from individuals who died without known neurological disorders. P- and E-selectin immunoreactivity was detected in large venules in the choroid plexus and subarachnoid space, but not in parenchymal microvessels. CD4+ T cells in the CSF expressed high levels of P-selectin glycoprotein ligand 1, and a subpopulation of circulating CD4+ T cells displayed P-selectin binding activity. Intercellular adhesion molecule 1, but not vascular cell adhesion molecule 1 or mucosal addressin cell adhesion molecule 1, was expressed in choroid plexus and subarachnoid space vessels. Based on these findings, we propose that T cells are recruited to the CSF through interactions between P-selectin/P-selectin ligands and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 in choroid plexus and subarachnoid space venules. These results support the overall hypothesis that activated memory T cells enter CSF directly from the systemic circulation and monitor the subarachnoid space, retaining the capacity to either initiate local immune reactions or return to secondary lymphoid organs. PMID:12829791

  12. Bilateral choroidal excavation in best vitelliform macular dystrophy.

    PubMed

    Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Fasce, Francesco; Bandello, Francesco

    2014-01-01

    Focal choroidal excavation (FCE) has recently been described as one or more localized areas of choroidal excavation on spectral-domain optical coherence tomography (SD-OCT). The authors describe a case of bilateral FCE in Best vitelliform macular dystrophy (VMD). SD-OCT revealed FCE in both eyes characterized by interruption of the internal segment-outer segment junction and the presence of subretinal hyporeflective space. This is the first report describing bilateral FCE in a distinct macular disorder and specifically with VMD. Future investigations are warranted to ascertain the involvement of other macular dystrophies with atrophic evolution and the impact of FCE on the clinical course. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:e8-e10.]. PMID:24512759

  13. Uveal Melanoma in the Peripheral Choroid Masquerading as Chronic Uveitis

    PubMed Central

    Feng, Lei; Zhu, Jiang; Gao, Tao; Li, Baizhou; Yang, Yabo

    2014-01-01

    ABSTRACT Purpose To describe a case of uveal melanoma in the peripheral choroid masquerading as chronic uveitis and to raise awareness about malignant masquerade syndromes. Case Report A 36-year-old Chinese woman presented from an outside ophthalmologist with a 6-month history of unilateral chronic uveitis unresponsive to medical therapy in the left eye. She was found to have a uveal melanoma in the retinal periphery and underwent successful enucleation of her left eye. The histopathological diagnosis confirmed the clinical diagnosis. Conclusions When uveal melanoma presents in an atypical way, the diagnosis is more difficult. This case highlights the uncommon presentations of malignant melanoma of the choroid. It provides valuable information on how peripheral uveal melanoma can present with clinical signs consistent with an anterior uveitis. PMID:25036546

  14. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    SciTech Connect

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. )

    1991-05-01

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

  15. Quantitative polarization and flow evaluation of choroid and sclera by multifunctional Jones matrix optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Sugiyama, S.; Hong, Y.-J.; Kasaragod, D.; Makita, S.; Miura, M.; Ikuno, Y.; Yasuno, Y.

    2016-03-01

    Quantitative evaluation of optical properties of choroid and sclera are performed by multifunctional optical coherence tomography. Five normal eyes, five glaucoma eyes and one choroidal atrophy eye are examined. The refractive error was found to be correlated with choroidal birefringence, polarization uniformity, and flow in addition to scleral birefringence among normal eyes. The significant differences were observed between the normal and the glaucoma eyes, as for choroidal polarization uniformity, flow and scleral birefringence. An automatic segmentation algorithm of retinal pigment epithelium and chorioscleral interface based on multifunctional signals is also presented.

  16. Choroidal Coloboma in a Case of Tay-Sachs Disease

    PubMed Central

    Ahmed, Nasreen Raees; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated. PMID:25295204

  17. Prognostic factors of choroidal melanoma in Slovenia, 1986–2008

    PubMed Central

    Budihna, Marjan; Drnovsek-Olup, Brigita; Andrejcic, Katrina Novak; Zupancic, Irena Brovet; Pahor, Dusica

    2016-01-01

    Introduction Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. Patients and methods From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Results Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. Conclusions It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation. PMID:27069456

  18. Choroidal coloboma in a case of tay-sachs disease.

    PubMed

    Ahmed, Nasreen Raees; Tripathy, Koushik; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated. PMID:25295204

  19. Photochemical Thrombosis Of Retinal And Choroidal Vessels Using Rose Bengal

    NASA Astrophysics Data System (ADS)

    Lewis, Mary Lou; Winward, Kirk; Watson, Brant D.; Hernandez, Eleut

    1989-09-01

    Rose bengal is an effective photosensitizing agent which interacts with argon green light to induce photochemical thrombosis of irradiated vessels. We used focal, low energy irradiation to occlude retinal and choroidal vessels in both albino and pigmented rabbits. Immediately after intravenous injection of rose bengal at concentrations of 10 and 20 mg/kg, irradiation was performed via a slit lamp-delivered argon green laser (514.5 nm) with the aid of fundus contact lens. In 11 eyes, arteries were treated with 50-100 interrupted bursts of 75u spot size at 0.2 sec and 40-100 mW (9 choroidal vessels, serous elevation of the retina, and disc neovascularization. In eight eyes choroidal vessels were irradiated with 10-20 mW, 15-60 sec, 500u spot size (31 choroidal vessels. There was minimal damage to surrounding tissue. Control eyes in all three groups irradiated utilizing the same parameters, but without rose bengal, demonstrated no evidence of thermal injury.

  20. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    PubMed Central

    2012-01-01

    Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID:22676316

  1. Antiangiogenic Effects of Topically Administered Multiple Kinase Inhibitor, Motesanib (AMG 706), on Experimental Choroidal Neovascularization in Mice

    PubMed Central

    Rho, Chang Rae; Kang, Seungbum; Park, Ki Cheol; Yang, Keum-Jin; Choi, Hyunsu

    2015-01-01

    Abstract Purpose: To investigate the effect of topical motesanib, an inhibitor of receptor tyrosine kinase, on experimental choroidal neovascularization (CNV). Methods: CNV was induced in 46 nine-week-old male C57BL/6 mice using fundus laser photocoagulation. The right eye of each mouse was treated with motesanib eye drop (4 times daily) and the left eye with vehicle eye drop (4 times daily) for 14 days. To evaluate changes in the CNV lesions, fluorescein angiography, immunofluorescence staining with CD34, and histological examinations were performed 14 days after CNV induction. The expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) in choroidal tissues was determined using western blot analysis to demonstrate the inhibitory effect of topically administered motesanib on intracellular signaling pathways involved in CNV development. Results: Fluorescein angiography showed that fluorescence leakage in eyes treated with topical motesanib was significantly less than in mice treated with vehicle (P=0.01). On immunofluorescence staining, the CD34-labeled area was smaller in topical motesanib-treated eyes (P<0.001). The expression level of phosphorylated ERK1/2 relative to that of total ERK1/2 decreased in eyes treated with topical motesanib compared with eyes treated with vehicle. Conclusion: Topical motesanib significantly reduced laser-induced CNV in the experimental mouse model. PMID:25255037

  2. Focal choroidal excavation in patients with central serous chorioretinopathy

    PubMed Central

    Luk, F O J; Fok, A C T; Lee, A; Liu, A T W; Lai, T Y Y

    2015-01-01

    Purpose To evaluate the prevalence and clinical features of focal choroidal excavation (FCE) in patients presenting with central serous chorioretinopathy (CSC). Methods This is a retrospective consecutive case series of consecutive patients with CSC who were referred for spectral domain optical coherence tomography (SD-OCT) between January 2010 and December 2011. Medical records were reviewed and clinical features including presence of FCE in SD-OCT, fluorescence angiography (FA), and indocyanine green angiography (ICGA) were studied. Results Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%) patients. FCE was associated with subretinal fluid in six eyes of six patients and serous pigment epithelial detachment in three eyes of two patients. The mean central subfield retinal thickness of CSC eyes with FCE was 283.7 μm, compared with 377.5 μm for CSC eyes without FCE (Mann–Whitney U-test, P=0.020). Five FCE eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity of all 11 eyes with FCE remained stable or improved at the last follow-up. Conclusion FCE is not an uncommon feature in patients with CSC and might be associated with choroidal hemodynamic disturbances. PMID:25853402

  3. Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia.

    PubMed

    Marinescu, Ileana; Udriştoiu, I; Marinescu, D

    2013-01-01

    Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis. Neuroimaging shows that in patients with poor evolution, cognitive dysfunction and therapeutic resistance, the presence of choroid plexus calcification associated with hippocampal, frontal, temporoparietal and cerebellar atrophies. Antipsychotics with high capacity to block D2 dopamine receptors (haloperidol model) can aggravate apoptotic mechanisms of the brain areas involved in cognition and disrupts the functional integrity of the BBB due to decreased of choroid plexus blood flow because of the narrowing of cerebral small vessels. Choroid plexus calcification may be a predictive indicator of poor evolution or of a neurodegenerative type. PMID:23771083

  4. Successful Nonoperative Management of HAGL (Humeral Avulsion of Glenohumeral Ligament) Lesion With Concurrent Axillary Nerve Injury in an Active-Duty US Navy SEAL.

    PubMed

    Ernat, Justin J; Bottoni, Craig R; Rowles, Douglas J

    2016-01-01

    Humeral avulsion of the glenohumeral ligament (HAGL) is a lesion that has been recognized as a cause of recurrent shoulder instability. To our knowledge there are no reports of successful return to full function in young, competitive athletes or return to manual labor following nonoperative management of a HAGL lesion. A 26-year-old Navy SEAL was diagnosed with a HAGL injury, and associated traction injury of the axillary nerve as well as a partial tear of the rotator cuff. Operative intervention was recommended; however, due to issues with training and with inability to properly rehab with the axillary nerve injury, surgical plans were delayed. Interestingly, the patient demonstrated both clinical and radiographic magnetic resonance imaging healing of his lesion over an 18-month period. At 18 months the patient had returned to full active duty without pain or instability as a Navy SEAL. PMID:27552458

  5. A Method for Extracting Suspected Parotid Lesions in CT Images using Feature-based Segmentation and Active Contours based on Stationary Wavelet Transform

    NASA Astrophysics Data System (ADS)

    Wu, T. Y.; Lin, S. F.

    2013-10-01

    Automatic suspected lesion extraction is an important application in computer-aided diagnosis (CAD). In this paper, we propose a method to automatically extract the suspected parotid regions for clinical evaluation in head and neck CT images. The suspected lesion tissues in low contrast tissue regions can be localized with feature-based segmentation (FBS) based on local texture features, and can be delineated with accuracy by modified active contour models (ACM). At first, stationary wavelet transform (SWT) is introduced. The derived wavelet coefficients are applied to derive the local features for FBS, and to generate enhanced energy maps for ACM computation. Geometric shape features (GSFs) are proposed to analyze each soft tissue region segmented by FBS; the regions with higher similarity GSFs with the lesions are extracted and the information is also applied as the initial conditions for fine delineation computation. Consequently, the suspected lesions can be automatically localized and accurately delineated for aiding clinical diagnosis. The performance of the proposed method is evaluated by comparing with the results outlined by clinical experts. The experiments on 20 pathological CT data sets show that the true-positive (TP) rate on recognizing parotid lesions is about 94%, and the dimension accuracy of delineation results can also approach over 93%.

  6. Effect of cytokeratin 17 on retinal pigment epithelium degeneration and choroidal neovascularization

    PubMed Central

    Shen, Yi; Zhuang, Pei; Xiao, Tao; Chiou, George CY

    2016-01-01

    AIM To study the effects of cytokeratin 17 (CK17) on sodium iodate (NaIO3) induced rat retinal pigment epithelium (RPE) degeneration, laser induced rat choroidal neovascularization (CNV), and oxidative stress of human retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cell (HUVEC). METHODS Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups, 10 rats in control group treated with solvent alone; 10 rats in NaIO3 group treated with solvent and 35 mg/kg NaIO3 injection through hypoglossal vein and 10 rats in CK17+NaIO3 group treated with 1% CK17 eye drop 3 times a day for 1wk before and 4wk after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Another 20 rats were randomly divided into 2 groups. Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1% CK17 eye drop before same as above; 10 rats in control were received Nd:YAG and treated with solvent. The development of choroidal neovascularization (CNV) was determined by fundus fluorescein angiography (FFA) performed on 4wk after laser. Methylthiazoly tetrazolium (MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro. RESULTS Four weeks after NaIO3 injection, the c-wave amplitude of ERG was 0.393±0.02 V in the control group, 0.184±0.018 V in NaIO3 group and 0.3±0.01 V in CK17+NaIO3 group. There was a significant reversal of the c-wave by CK17 as compared to NaIO3 group (P<0.01). Four weeks after laser, the size of the CNV lesion was 2.57±0.27 mm2 in control group and 1.64±0.08 mm2 in CK17 group. The lesion size significantly diminished in CK17 group (P<0.01). The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 µg/mL and enhanced the injury in HUVECs at different concentrations. CONCLUSION CK17 can significantly protect RPE from NaIO3 induced degeneration in vivo and in vitro and

  7. Surgery for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration: Ophthalmic Findings

    PubMed Central

    2005-01-01

    Purpose To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). Design Randomized clinical trial. Participants Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). Methods Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. Main Outcome Measure A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. Results Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. Conclusions Submacular surgery, as performed in this

  8. Characterization of Lesion Formation and Bubble Activities during High Intensity Focused Ultrasound Ablation using Temperature-Derived Parameters

    PubMed Central

    Hsiao, Yi-Sing; Kumon, Ronald E.; Deng, Cheri X.

    2013-01-01

    Successful high-intensity focused ultrasound (HIFU) thermal tissue ablation relies on accurate information of the tissue temperature and tissue status. Often temperature measurements are used to predict and monitor the ablation process. In this study, we conducted HIFU ablation experiments with ex vivo porcine myocardium tissue specimens to identify changes in temperature associated with tissue coagulation and bubble/cavity formation. Using infrared (IR) thermography and synchronized bright-field imaging with HIFU applied near the tissue surface, parameters derived from the spatiotemporal evolution of temperature were correlated with HIFU-induced lesion formation and overheating, of which the latter typically results in cavity generation and/or tissue dehydration. Emissivity of porcine myocardium was first measured to be 0.857 ± 0.006 (n = 3). HIFU outcomes were classified into non-ablative, normal lesion, and overheated lesion. A marked increase in the rate of temperature change during HIFU application was observed with lesion formation. A criterion using the maximum normalized second time derivative of temperature change provided 99.1% accuracy for lesion identification with a 0.05 s−1 threshold. Asymmetric temperature distribution on the tissue surface was observed to correlate with overheating and/or bubble generation. A criterion using the maximum displacement of the spatial location of the peak temperature provided 90.9% accuracy to identify overheated lesion with a 0.16 mm threshold. Spatiotemporal evolution of temperature obtained using IR imaging allowed determination of the cumulative equivalent minutes at 43 °C (CEM43) for lesion formation to be 170 min. Similar temperature characteristics indicative of lesion formation and overheating were identified for subsurface HIFU ablation. These results suggest that parameters derived from temperature changes during HIFU application are associated with irreversible changes in tissue and may provide useful

  9. Characterization of Lesion Formation and Bubble Activities during High Intensity Focused Ultrasound Ablation using Temperature-Derived Parameters.

    PubMed

    Hsiao, Yi-Sing; Kumon, Ronald E; Deng, Cheri X

    2013-09-01

    Successful high-intensity focused ultrasound (HIFU) thermal tissue ablation relies on accurate information of the tissue temperature and tissue status. Often temperature measurements are used to predict and monitor the ablation process. In this study, we conducted HIFU ablation experiments with ex vivo porcine myocardium tissue specimens to identify changes in temperature associated with tissue coagulation and bubble/cavity formation. Using infrared (IR) thermography and synchronized bright-field imaging with HIFU applied near the tissue surface, parameters derived from the spatiotemporal evolution of temperature were correlated with HIFU-induced lesion formation and overheating, of which the latter typically results in cavity generation and/or tissue dehydration. Emissivity of porcine myocardium was first measured to be 0.857 ± 0.006 (n = 3). HIFU outcomes were classified into non-ablative, normal lesion, and overheated lesion. A marked increase in the rate of temperature change during HIFU application was observed with lesion formation. A criterion using the maximum normalized second time derivative of temperature change provided 99.1% accuracy for lesion identification with a 0.05 s(-1) threshold. Asymmetric temperature distribution on the tissue surface was observed to correlate with overheating and/or bubble generation. A criterion using the maximum displacement of the spatial location of the peak temperature provided 90.9% accuracy to identify overheated lesion with a 0.16 mm threshold. Spatiotemporal evolution of temperature obtained using IR imaging allowed determination of the cumulative equivalent minutes at 43 °C (CEM 43) for lesion formation to be 170 min. Similar temperature characteristics indicative of lesion formation and overheating were identified for subsurface HIFU ablation. These results suggest that parameters derived from temperature changes during HIFU application are associated with irreversible changes in tissue and may provide useful

  10. Characterization of lesion formation and bubble activities during high-intensity focused ultrasound ablation using temperature-derived parameters

    NASA Astrophysics Data System (ADS)

    Hsiao, Yi-Sing; Kumon, Ronald E.; Deng, Cheri X.

    2013-09-01

    Successful high-intensity focused ultrasound (HIFU) thermal tissue ablation relies on accurate information of the tissue temperature and tissue status. Often temperature measurements are used to predict and monitor the ablation process. In this study, we conducted HIFU ablation experiments with ex vivo porcine myocardium tissue specimens to identify changes in temperature associated with tissue coagulation and bubble/cavity formation. Using infrared (IR) thermography and synchronized bright-field imaging with HIFU applied near the tissue surface, parameters derived from the spatiotemporal evolution of temperature were correlated with HIFU-induced lesion formation and overheating, of which the latter typically results in cavity generation and/or tissue dehydration. Emissivity of porcine myocardium was first measured to be 0.857 ± 0.006 (n = 3). HIFU outcomes were classified into non-ablative, normal lesion, and overheated lesion. A marked increase in the rate of temperature change during HIFU application was observed with lesion formation. A criterion using the maximum normalized second time derivative of temperature change provided 99.1% accuracy for lesion identification with a 0.05 s-1 threshold. Asymmetric temperature distribution on the tissue surface was observed to correlate with overheating and/or bubble generation. A criterion using the maximum displacement of the spatial location of the peak temperature provided 90.9% accuracy to identify overheated lesion with a 0.16 mm threshold. Spatiotemporal evolution of temperature obtained using IR imaging allowed determination of the critical cumulative equivalent minutes at 43 °C (CEM43) for lesion formation to be 170 min. Similar temperature characteristics indicative of lesion formation and overheating were identified for subsurface HIFU ablation. These results suggest that parameters derived from temperature changes during HIFU application are associated with irreversible changes in tissue and may provide

  11. Effective Treatment with Intravitreal Injection of Bevacizumab for Exudative Retinal Detachment Secondary to Choroidal Metastasis of Non-Small Cell Lung Carcinoma

    PubMed Central

    Yasui, Hirotoshi; Sato, Kazuhide; Takeyama, Yoshihiro; Nishihara, Hiroaki; Maeda, Matsuyoshi; Gonda, Hideo; Suzuki, Ryujiro

    2015-01-01

    Patient: Male, 68 Final Diagnosis: Non-small cell lung cancer Symptoms: — Medication: — Clinical Procedure: TBLB • PET • OCT • fluorescence angiography Specialty: Oncology Objective: Challenging differential diagnosis Background: Visual disturbance caused by cancer metastasis from other organs is one of the largest challenges to cancer patients’ quality of life (QOL). Lung cancer is the most frequent primary site of choroidal metastasis in men, but improvement of visual disturbance has not always been emphasized in lung cancers. Recently intravitreal bevacizumab is a newer modality being tried for local control of choroidal metastases. Case Report: A 68-year-old man was admitted the hospital with complaint of visual disturbance in his left eye. He was diagnosed with lung adenocarcinoma cT2N0M1b (OSS, OTH) stage IV. The ophthalmologic evaluation showed exudative fluid, which caused retinal detachment under the retina. Fluorescence angiography showed granular hyperfluorescence with leakage consistent with a tumor. He received radiotherapy for bone metastasis and systematic chemotherapy with carboplatin, pemetrexed, and bevacizumab, as well as intravitreal injection of bevacizumab 1.25 mg to improve the visual disturbance. His visual symptom and retinal detachment improved until he died. An autopsy revealed that the metastatic lesion in his left eye was totally cured macroscopically and microscopically. Conclusions: We report a case of exudative retinal detachment secondary to a metastatic choroidal tumor from lung adenocarcinoma, which was treated with chemotherapy and intravitreal injection of bevacizumab. Although he finally died of lung cancer, he maintained his visual QOL and autopsy revealed complete cure of the choroidal metastasis. PMID:26460101

  12. Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion.

    PubMed

    Kavoussi, S K; Witz, C A; Binkley, P A; Nair, A S; Lebovic, D I

    2009-10-01

    The aim of this study was to investigate whether peroxisome proliferator-activated receptor (PPAR)-gamma activation has an effect on the attachment of endometrial cells to peritoneal mesothelial cells in a well-established in vitro model of the early endometriotic lesion. The endometrial epithelial cell line EM42 and mesothelial cell line LP9 were used for this study. EM42 cells, LP9 cells or both were treated with the PPAR-gamma agonist ciglitazone (CTZ) at varying concentrations (10, 20 and 40 microM) x 48 h with subsequent co-culture of EM42 and LP9 cells. The rate of EM42 attachment and invasion through LP9 cells was then assessed and compared with control (EM42 and LP9 cells co-cultured without prior treatment with CTZ). Next, attachment of CTZ-treated and untreated EM42 cells to hyaluronic acid (HA), a cell adhesion molecule (CAM) on peritoneal mesothelial cells, were assessed. Although there was no difference in EM42 attachment when LP9 cells alone were treated with CTZ, treatment of EM42 cells with 40 microM CTZ decreased EM42 attachment to LP9 cells by 27% (P < 0.01). Treatment of both EM42 and LP9 cells with 40 microM CTZ decreased EM42 attachment to LP9 by 37% (P < 0.01). Treatment of EM42 cells with 40 microM CTZ decreased attachment to HA by 66% (P = 0.056). CTZ did not decrease invasion of EM42 cells through the LP9 monolayer. CTZ may inhibit EM42 cell proliferation. In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. PMID:19643817

  13. Staged Radiosurgical Ablation for Choroid Melanoma: A Case Report with Emphasis on the Role of Patient Preparation, Treatment Planning, and Precision of Delivery

    PubMed Central

    Janiga, Piotr

    2016-01-01

    The aim of reporting this case of choroid melanoma of the left eye is to introduce the in-house-designed treatment planning protocol for fractionated radiosurgical ablation of an intraocular lesion. This is a clinical case with emphasis on treatment preparation and delivery using the Accuray CyberKnife Robotic Radiosurgery System (Accuray, Sunnyvale, CA, USA) for a patient immobilized with a head mask and our in-house-made eye fixation system. PMID:27335716

  14. [Foot lesions].

    PubMed

    Stelzner, C; Schellong, S; Wollina, U; Machetanz, J; Unger, L

    2013-11-01

    The foot is the target organ of a variety of internal diseases. Of upmost importance is the diabetic foot syndrome (DFS). Its complex pathophysiology is driven by the diabetic neuropathy, a vastly worsening effect is contributed by infection and ischemia. Seemingly localised lesions have the potential for phlegmone and septicaemia if not diagnosed and drained early. The acral lesions of peripheral artery occlusive disease (PAOD) have unique features as well. However, their life-threatening potential is lower than that of DFS even if the limb is critical. Notably, isolated foot lesions with a mere venous cause may arise from insufficient perforator veins; the accompanying areas of haemosiderosis will lead the diagnostic path. Cholesterol embolization (blue toe syndrome, trash foot) elicits a unique clinical picture and will become more frequent with increasing numbers of catheter-based procedures. Finally, descriptions are given of podagra and of foot mycosis as disease entities not linked to perfusion. The present review focuses on the depiction of disease and its diagnosis, leaving therapeutic considerations untouched. PMID:24114468

  15. Elevated thymidine phosphorylase activity in psoriatic lesions accounts for the apparent presence of an epidermal growth inhibitor, but is not in itself growth inhibitory

    SciTech Connect

    Hammerberg, C.; Fisher, G.J.; Voorhees, J.J.; Cooper, K.D. )

    1991-08-01

    An apparent tissue-specific growth inhibitor, or chalone, obtained from psoriatic lesions was tentatively identified in the 100-kDa fraction based upon inhibition of DNA synthesis, as measured by (3H)-thymidine uptake by a squamous cell carcinoma cell line, SCC 38. This fraction, however, failed to inhibit SCC 38 cell growth when assessed directly in a neutral red uptake assay. Characterization of the inhibitor of (3H)-thymidine uptake revealed it to have biochemical properties identical to thymidine phosphorylase: (1) molecular weight close to 100 kDa, (2) isoelectric point of 4.2, and (3) thymidine phosphorylase enzyme activity. Thus, the authors conclude that its ability to inhibit (3H)-thymidine uptake was due to thymidine catabolism rather than inhibition of DNA synthesis or growth inhibition. Examination of thymidine phosphorylase activity in keratome biopsies from psoriatic and normal skin demonstrated a twentyfold increase in activity in psoriatic lesions relative to non-lesional or normal skin. This increase in metabolism of thymidine was due to thymidine phosphorylase rather than uridine phosphorylase activity. The correlation between increased thymidine phosphorylase activity and increased keratinocyte proliferation in vitro (cultured) and in vivo (psoriasis), suggests that this enzyme may play a critical role in providing the thymidine necessary for keratinocyte proliferation.

  16. Retinal hemorrhagic lesions from femtosecond visible laser pulses

    NASA Astrophysics Data System (ADS)

    Stein, Cindy D.; Toth, Cynthia A.; Cain, Clarence P.; Noojin, Gary D.; Stolarski, David J.; Rockwell, Benjamin A.; Roach, William P.

    1994-08-01

    We present our clinical evaluation of hemorrhagic and non-hemorrhagic 90 fs single pulses in rabbits and primates. The rabbit and primate eye present unique in vivo models for evaluation of retinal and choroidal laser induced hemorrhages with distinct differences in their retinal anatomy. We found two different hemorrhagic events to occur in the posterior pole with delivery of 90 fs pulses. First, in the Dutch Belted rabbit, we found large amounts of energy per pulse (from 20 to 60 times ED50) were required for formation of subretinal hemorrhages. Second, in the Rhesus monkey, we found significant numbers of small intraretinal hemorrhages from relatively low energy 90 fs pulses. Both the Dutch Belted rabbit and the Rhesus monkey failed to consistently show subretinal hemorrhagic lesions form very high pulse energies. Our findings suggest more energy absorption at the level of the retinal circulation than the choroidal circulation with our pulse parameters. The effects of the laser on the retinal circulation may be due to the use of a wavelength of 580 nm. At this wavelength the oxyhemoglobin to melanin absorption ratio is nearly at its peak (approximately 0.40), perhaps allowing improved absorption in the retinal vasculature. One precaution with this finding, however, are the distinct differences between primate and non-primate ocular systems. Further studies are required to resolve the differences in damage at the level of the RPE and choroid between rabbits and primates.

  17. Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease

    PubMed Central

    Kur, Joanna; Newman, Eric A.; Chan-Ling, Tailoi

    2012-01-01

    We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored. PMID:22580107

  18. Automated three-dimensional choroidal vessel segmentation of 3D 1060 nm OCT retinal data

    PubMed Central

    Kajić, Vedran; Esmaeelpour, Marieh; Glittenberg, Carl; Kraus, Martin F.; Honegger, Joachim; Othara, Richu; Binder, Susanne; Fujimoto, James G.; Drexler, Wolfgang

    2012-01-01

    A fully automated, robust vessel segmentation algorithm has been developed for choroidal OCT, employing multiscale 3D edge filtering and projection of “probability cones” to determine the vessel “core”, even in the tomograms with low signal-to-noise ratio (SNR). Based on the ideal vessel response after registration and multiscale filtering, with computed depth related SNR, the vessel core estimate is dilated to quantify the full vessel diameter. As a consequence, various statistics can be computed using the 3D choroidal vessel information, such as ratios of inner (smaller) to outer (larger) choroidal vessels or the absolute/relative volume of choroid vessels. Choroidal vessel quantification can be displayed in various forms, focused and averaged within a special region of interest, or analyzed as the function of image depth. In this way, the proposed algorithm enables unique visualization of choroidal watershed zones, as well as the vessel size reduction when investigating the choroid from the sclera towards the retinal pigment epithelium (RPE). To the best of our knowledge, this is the first time that an automatic choroidal vessel segmentation algorithm is successfully applied to 1060 nm 3D OCT of healthy and diseased eyes. PMID:23304653

  19. Angiographic results of retinal-retinal anastomosis and retinal-choroidal anastomosis after treatments in eyes with retinal angiomatous proliferation

    PubMed Central

    Saito, Masaaki; Iida, Tomohiro; Kano, Mariko; Itagaki, Kanako

    2012-01-01

    Background The purpose of this study was to evaluate the angiographic results of retinal-retinal anastomosis (RRA) and retinal-choroidal anastomosis (RCA) for eyes with retinal angiomatous proliferation (RAP) after treatment with intravitreal bevacizumab injections as monotherapy or intravitreal bevacizumab combined with photodynamic therapy. Methods In this interventional, consecutive case series, we retrospectively reviewed five naïve eyes from four patients (mean age 80 years) treated with three consecutive monthly intravitreal bevacizumab (1.25 mg/0.05 mL) injections as initial treatment, and followed up for at least 3 months. In cases with over 3 months of follow-up and having recurrence of RAP or leakage by fluorescein angiography, retreatment was performed with a single intravitreal bevacizumab injection and photodynamic therapy. Results Indocyanine green angiography showed RRA in three eyes with subretinal neovascularization and RCA in two eyes with choroidal neovascularization at baseline. At 3 months after baseline (month 3), neither the RRA nor RCA was occluded in any eye on indocyanine green angiography. Retreatment with intravitreal bevacizumab plus photodynamic therapy was performed in three eyes at months 3 (persistent leakage on fluorescein angiography), 6, and 7 (recurrence of RAP lesion), which achieved obvious occlusion of the RRA and RCA. Mean best-corrected visual acuity improved from 0.13 to 0.21 at month 3 (P = 0.066). No complications or systemic adverse events were noted. Conclusion Although intravitreal bevacizumab for RAP was effective in improving visual acuity during short-term follow-up, intravitreal bevacizumab could not achieve complete occlusion of RRA and RCA, which could lead to recurrence of a RAP lesion and exudation. Retreatment with intravitreal bevacizumab plus photodynamic therapy ultimately achieved complete occlusion of the RRA and RCA. PMID:22969283

  20. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity.

    PubMed

    Azevedo, Michelle de C S; Rosa, Patricia S; Soares, Cleverson T; Fachin, Luciana R V; Baptista, Ida Maria F D; Woods, William J; Garlet, Gustavo P; Trombone, Ana Paula F; Belone, Andrea de F F

    2015-01-01

    Jorge Lobo's disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  1. Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

    PubMed Central

    Azevedo, Michelle de C. S.; Rosa, Patricia S.; Soares, Cleverson T.; Fachin, Luciana R. V.; Baptista, Ida Maria F. D.; Woods, William J.; Garlet, Gustavo P.

    2015-01-01

    Jorge Lobo’s disease (JLD) is a chronic infection that affects the skin and subcutaneous tissues. Its etiologic agent is the fungus Lacazia loboi. Lesions are classified as localized, multifocal, or disseminated, depending on their location. Early diagnosis and the surgical removal of lesions are the best therapeutic options currently available for JLD. The few studies that evaluate the immunological response of JLD patients show a predominance of Th2 response, as well as a high frequency of TGF-β and IL-10 positive cells in the lesions; however, the overall immunological status of the lesions in terms of their T cell phenotype has yet to be determined. Therefore, the objective of this study was to evaluate the pattern of Th1, Th2, Th17 and regulatory T cell (Treg) markers mRNA in JLD patients by means of real-time PCR. Biopsies of JLD lesions (N = 102) were classified according to their clinical and histopathological features and then analyzed using real-time PCR in order to determine the expression levels of TGF-β1, FoxP3, CTLA4, IKZF2, IL-10, T-bet, IFN-γ, GATA3, IL-4, IL-5, IL-13, IL-33, RORC, IL-17A, IL-17F, and IL-22 and to compare these levels to those of healthy control skin (N = 12). The results showed an increased expression of FoxP3, CTLA4, TGF-β1, IL-10, T-bet, IL-17F, and IL-17A in lesions, while GATA3 and IL-4 levels were found to be lower in diseased skin than in the control group. When the clinical forms were compared, TGF-β1 was found to be highly expressed in patients with a single localized lesion while IL-5 and IL-17A levels were higher in patients with multiple/disseminated lesions. These results demonstrate the occurrence of mixed T helper responses and suggest the dominance of regulatory T cell activity, which could inhibit Th-dependent protective responses to intracellular fungi such as L. loboi. Therefore, Tregs may play a key role in JLD pathogenesis. PMID:26700881

  2. Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

    PubMed Central

    2009-01-01

    Background Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection. Methods NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays. Results We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients. Conclusion Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression. PMID:19531227

  3. Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial

    PubMed Central

    Song, I-H; Hermann, KG; Haibel, H; Althoff, CE; Listing, J; Burmester, GR; Krause, A; Bohl-Bühler, M; Freundlich, B; Rudwaleit, M; Sieper, J

    2011-01-01

    Purpose To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years. Methods Patients were randomly assigned to etanercept (n=40) or sulfasalazine (n=36) treatment over 48 weeks. All patients showed active inflammatory lesions (bone marrow oedema) on MRI in either the sacroiliac joints or the spine. MRI was performed at weeks 0, 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists, blinded for treatment arm and MRI time point. Results In the etanercept group, the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly (p=0.02) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48. A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48, respectively (p=0.01). The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group (p=0.04 for difference). 50% of patients reached clinical remission in the etanercept group versus 19% in the sulfasalazine group at week 48. Conclusion In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients. This effect correlated with a good clinical response in the etanercept group. PMID:21372193

  4. In vivo retinal optical coherence tomography at 1040 nm - enhanced penetration into the choroid

    NASA Astrophysics Data System (ADS)

    Unterhuber, Angelika; Povazay, B.; Hermann, B.; Sattmann, H.; Chavez-Pirson, A.; Drexler, W.

    2005-05-01

    For the first time in vivo retinal imaging has been performed with a new compact, low noise Yb-based ASE source operating in the 1 μm range (NP Photonics, λc = 1040 nm, Δλ = 50 nm, Pout = 30 mW) at the dispersion minimum of water with ~7 μm axial resolution. OCT tomograms acquired at 800 nm are compared to those achieved at 1040 nm showing about 200 μm deeper penetration into the choroid below the retinal pigment epithelium. Retinal OCT at longer wavelengths significantly improves the visualization of the retinal pigment epithelium/choriocapillaris/choroids interface and superficial choroidal layers as well as reduces the scattering through turbid media and therefore might provide a better diagnosis tool for early stages of retinal pathologies such as age related macular degeneration which is accompanied by choroidal neovascularization, i.e., extensive growth of new blood vessels in the choroid and retina.

  5. Choroidal malignant melanoma with no extraocular extension presenting as orbital cellulitis.

    PubMed

    Nalcaci, Serhad; Palamar, Melis; Yaman, Banu; Akalin, Taner; Mentes, Jale

    2016-10-01

    This report describes a patient with choroidal malignant melanoma presenting as orbital cellulitis without extraocular tumor extension. It is an interventional case report with histopathologic correlation. A 68-year-old male presented with a 3-day history of painful hyperemia and swelling in the right eye. The examination showed edematous eyelids, mechanical ptosis and chemosis with conjunctival injection. B-scan ultrasonography showed a mass with medium level echogenicity that filled the vitreous cavity. Magnetic resonance imaging showed a solid choroidal mass with hemorrhagic and inflammatory changes with no obvious extraocular extension. Due to these suggestive findings of choroidal melanoma the right eye was enucleated. A spindle cell choroidal melanoma including intense pigmentation and necrosis was confirmed by histopathological examination. Although rare; choroidal melanoma may present as orbital cellulitis, particularly when the tumor is necrotic. PMID:27463451

  6. 99Tc-MDP treatment for the therapy of rheumatoid arthritis, choroidal neovascularisation and Graves' ophthalmopathy

    PubMed Central

    WU, QIAN; NI, YANG; YANG, QINGRUI; SUN, HONGSHENG

    2016-01-01

    Technetium 99 conjugated with methylene diphosphonate, which is an anti-inflammatory drug, can inhibit macrophage infiltration and downregulate a number of proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Recently, numerous studies have indicated that it could improve rheumatoid arthritis (RA) activity by upregulating the frequency of peripheral γδ T cells and cluster of differentiation CD4+CD25+Foxp3+ Tregs, affecting the serum cytokine environment, inhibiting osteoclast formation and reducing the concentrations of rheumatoid factor-immunoglobulin M (IgM)/IgG/IgA. As well, it may have a therapeutic role for choroidal neovascularisation (CNV) and Graves' ophthalmopathy (GO). Therefore, it will be a valuable choice in the treatment of RA, CNV and GO. PMID:27073620

  7. Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization

    PubMed Central

    Huang, Jiahn-Dar; Amaral, Juan; Lee, Jung Wha; Larrayoz, Ignacio M.; Rodriguez, Ignacio R.

    2012-01-01

    Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer’s disease and age-related macular degeneration. Sterculic acid demonstrated to be 5–10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration. PMID:22342272

  8. E-cadherin, N-cadherin Expression and Histologic Characterization of Canine Choroid Plexus Tumors.

    PubMed

    Reginato, A; Girolami, D; Menchetti, L; Foiani, G; Mandara, M T

    2016-07-01

    Choroid plexus tumors (CPTs) are reported with an increasing incidence in dogs, and they call for a reexamination of histologic features and criteria of classification corresponding to their biological behavior. In this study, the human World Health Organization classification was applied to 16 canine CPTs, and the expression of molecules involved in neoplastic cell adhesion (E-cadherin, N-cadherin), invasion (doublecortin), and proliferation (Ki-67) was investigated. Mitotic index was found to be the main criterion for grading CPTs. Cell density and multilayering of papillae were also statistically associated with histologic grade. Intraventricular spread and parenchymal invasion was observed for tumors showing histologic benign features. E-cadherin was expressed in all CPT grades, independent of tumor invasion. N-cadherin immunolabeling was more expressed in grade I than high-grade CPTs, whereas doublecortin expression was not detected in CPTs. An increasing proliferative activity was observed in relation with histologic grade. PMID:26792846

  9. Aging. Aging-induced type I interferon signaling at the choroid plexus negatively affects brain function

    PubMed Central

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M.; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2016-01-01

    Age-associated cognitive decline is affected by factors produced inside and outside the brain. We found in aged mice and humans, that the choroid plexus (CP), an epithelial interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent expression profile, often associated with anti-viral responses. This signature was induced by brain-derived signals present in the cerebrospinal fluid of aged mice. Blocking IFN-I signaling within the brain of cognitively-impaired aged mice, using IFN-I receptor neutralizing antibody, led to partial restoration of cognitive function and hippocampal neurogenesis, and reestablished IFN-II-dependent CP activity, lost in aging. Our data identify an aging-induced IFN-I signature at the CP, and demonstrate its negative influence on brain function, thereby suggesting a potential target for therapeutic intervention for age-related cognitive decline. PMID:25147279

  10. Cellular reactions of the choroid plexus induced by peripheral nerve injury.

    PubMed

    Joukal, Marek; Klusáková, Ilona; Solár, Peter; Kuklová, Adéla; Dubový, Petr

    2016-08-15

    The choroid plexus (CP) of brain ventricles forms the blood-cerebrospinal fluid (blood-CSF) barrier that is involved in many diseases affecting the central nervous system (CNS). We used ED1 and ED2 immunostaining to investigate epiplexus cell changes in rat CP after chronic constriction injury (CCI). In contrast to naïve CP, the CP of sham-operated rats showed an increase in the number of ED1+ cells of a similar magnitude during all periods of survival up to 3 weeks, while the number of ED2+ increased only at 3 days from operation. In comparison to naïve and sham-operated animals, the number of ED1+ and ED2+ cells in the epiplexus position increased with the duration of nerve compression. We detected no or negligible cell proliferation in the CP after sham- or CCI-operation. This suggests that increased number of ED1+ and ED2+ cells in the epiplexus position of the CP is derived from peripheral monocytes passing through altered blood-CSF barrier. The changes in epiplexus cells indicate that the CP reacts to tissue injury after the surgical approach itself and that the response to peripheral nerve lesion is greater. This suggests a role for an altered blood-CSF barrier allowing for propagation of signal molecules from damaged tissue and nerve to the CNS. PMID:27291457

  11. Bilateral Diffuse Uveal Melanocytic Proliferation Presenting as a Giant Unilateral Choroidal Nevus: A Case Report

    PubMed Central

    Menezes, Carlos; Carvalho, Rui; Neves-Martins, Joana; Teixeira, Carla

    2015-01-01

    Background/Aims The aim of our study was to report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) with a markedly asymmetric presentation and fundoscopic response to palliative chemotherapy. Case Report We report a 67-year-old Caucasian man who presented with vision loss in his right eye. The best-corrected visual acuities were 2/10 in the right eye and 10/10 in the left eye, and biomicroscopy revealed bilateral mild cataracts. Fundoscopy of the right eye showed a macular flat and pigmented lesion extending beyond the posterior pole with areas of giraffe-type pigmentation and an overlying exudative retinal detachment. Nothing remarkable was detected in the left eye apart from a small round hypopigmented area of retinal pigment epithelium atrophy in the papillomacular bundle. BDUMP was diagnosed, and the workup for systemic malignancy revealed a pulmonary adenocarcinoma. After chemotherapy, not only did the right eye's visual acuity improve and the serous detachment resolve, but also the pigmentation decreased. Conclusion BDUMP presentation can be markedly asymmetric and resemble a giant unilateral choroidal nevus. Response to chemotherapy was unique not only for the usual retinal detachment resolution, but also because of an evident regression of pigmentation. PMID:27171585

  12. Choroidal abnormalities and masquerade syndromes confounding the diagnosis of laser-induced eye injuries

    NASA Astrophysics Data System (ADS)

    Hacker, Henry D.; Zwick, Harry; Brown, Jeremiah, Jr.; Dicks, Ronald; Cheramie, Rachel; Stuck, Bruce E.

    2005-04-01

    The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.

  13. Targeting Platelet-Derived Growth Factor Receptor β(+) Scaffold Formation Inhibits Choroidal Neovascularization.

    PubMed

    Strittmatter, Karin; Pomeroy, Hayley; Marneros, Alexander G

    2016-07-01

    Neovascular age-related macular degeneration is among the most common causes of irreversible blindness and manifests with choroidal neovascularization (CNV). Anti-vascular endothelial growth factor-A therapies are only partially effective and their chronic administration may impair functions of the choriocapillaris and retina. Thus, novel therapeutic targets are needed urgently. We have observed in a laser-induced model of CNV that a platelet-derived growth factor receptor β positive (PDGFRβ(+)) scaffold is formed before infiltration of neovessels into this scaffold to form CNV lesions, and that this scaffold limits the extent of neovascularization. Based on these observations we hypothesized that ablation of proliferating PDGFRβ(+) cells to prevent the formation of this scaffold might inhibit CNV growth and present a novel therapeutic approach for neovascular age-related macular degeneration. To test this hypothesis we targeted proliferating PDGFRβ(+) cells through independent distinct approaches after laser injury: i) by using an inducible genetic model to inhibit specifically proliferating PDGFRβ(+) cells, ii) by treating mice with a neutralizing anti-PDGFRβ antibody, iii) by administering an anti-PDGF-AB/BB aptamer, and iv) by using small chemical inhibitor approaches. The results show that therapeutic targeting of proliferating PDGFRβ(+) cells potently inhibits the formation of the pericyte-like scaffold, with concomitant attenuation of CNV. Moreover, we show that early inhibition of PDGFRβ(+) cell proliferation before neovessel formation is sufficient to inhibit scaffold formation and neovascularization. PMID:27338108

  14. Are Articular Cartilage Lesions and Meniscus Tears Predictive of IKDC, KOOS, and Marx Activity Level Outcomes after ACL Reconstruction? A 6-Year Multicenter Cohort Study

    PubMed Central

    Cox, Charles L.; Huston, Laura J.; Dunn, Warren R.; Reinke, Emily K.; Nwosu, Samuel K.; Parker, Richard D.; Wright, Rick W.; Kaeding, Christopher C.; Marx, Robert G.; Amendola, Annunziata; McCarty, Eric C.; Wolf, Brian R.; Harrell, Frank E.; Spindler, Kurt P.

    2014-01-01

    Background Identifying risk factors for inferior outcomes after ACL reconstruction (ACLR) is important for prognosis and future treatment. The goal of this study was to determine whether articular cartilage and meniscal variables are predictive of 3 validated sports outcome instruments after ACLR. Hypothesis/Purpose We hypothesized that articular cartilage lesions and meniscus tears/treatment would be predictors of the IKDC, KOOS (all 5 subscales), and Marx activity level at 6 years following ACLR. Study Design Prospective cohort, Level 1 Methods Between 2002 and 2004, 1512 ACLR subjects were prospectively enrolled and followed longitudinally with the IKDC, KOOS, and Marx activity score completed at entry, 2, and 6 years. A logistic regression model was built incorporating variables from patient demographics, surgical technique, articular cartilage injuries, and meniscus tears/treatment to determine the predictors (risk factors) of IKDC, KOOS, and Marx at 6 years. Results We completed a minimum follow-up on 86% (1307/1512) of our cohort at 6 years. The cohort was 56% male, had a median age of 23 years at the time of enrollment, with 76% reporting a non-contact injury mechanism. Incidence of concomitant pathology at the time of surgery consisted of the following: articular cartilage (medial femoral condyle [MFC]-25%, lateral femoral condyle [LFC]-20%, medial tibial plateau [MTP]-6%, lateral tibial plateau [LTP]-12%, patella-20%, trochlear-9%) and meniscal (medial-38%, lateral-46%). Both articular cartilage lesions and meniscal tears were significant predictors of 6-year outcomes on IKDC and KOOS. Grade 3 or 4 articular cartilage lesions (excluding patella) significantly reduced IKDC and KOOS scores at 6 years. IKDC demonstrated worse outcomes with the presence of a grade 3-4 chondral lesion on the MFC, MTP, and LFC. Likewise, KOOS was negatively affected by cartilage injury. The sole significant predictor of reduced Marx activity was the presence of a grade 4 lesion

  15. Three-dimensional choroidal segmentation in spectral OCT volumes using optic disc prior information

    NASA Astrophysics Data System (ADS)

    Hu, Zhihong; Girkin, Christopher A.; Hariri, Amirhossein; Sadda, SriniVas R.

    2016-03-01

    Recently, much attention has been focused on determining the role of the peripapillary choroid - the layer between the outer retinal pigment epithelium (RPE)/Bruchs membrane (BM) and choroid-sclera (C-S) junction, whether primary or secondary in the pathogenesis of glaucoma. However, the automated choroidal segmentation in spectral-domain optical coherence tomography (SD-OCT) images of optic nerve head (ONH) has not been reported probably due to the fact that the presence of the BM opening (BMO, corresponding to the optic disc) can deflect the choroidal segmentation from its correct position. The purpose of this study is to develop a 3D graph-based approach to identify the 3D choroidal layer in ONH-centered SD-OCT images using the BMO prior information. More specifically, an initial 3D choroidal segmentation was first performed using the 3D graph search algorithm. Note that varying surface interaction constraints based on the choroidal morphological model were applied. To assist the choroidal segmentation, two other surfaces of internal limiting membrane and innerouter segment junction were also segmented. Based on the segmented layer between the RPE/BM and C-S junction, a 2D projection map was created. The BMO in the projection map was detected by a 2D graph search. The pre-defined BMO information was then incorporated into the surface interaction constraints of the 3D graph search to obtain more accurate choroidal segmentation. Twenty SD-OCT images from 20 healthy subjects were used. The mean differences of the choroidal borders between the algorithm and manual segmentation were at a sub-voxel level, indicating a high level segmentation accuracy.

  16. Maturation of Rb+ and PAH accumulation by rabbit anterior uvea and choroid plexus

    SciTech Connect

    Krupin, T.; Fritz, C.; Becker, B.

    1985-02-01

    In vitro accumulation of radioactive para-aminohippuric acid (/sup 3/H-PAH) and rubidium (/sup 86/Rb+) by the anterior uvea, ciliary processes, and the choroid plexus was evaluated in tissues from newborn and various aged rabbits. Accumulation of PAH was present in the anterior uvea at 1 day of age (tissue to media ratio, T/M, of 2.1 +/- 0.2) and remained at this level for the first 14 days of life. Accumulation did not rise to adult levels until 21 days of age (T/M 5.5 +/- 0.6). Rubidium accumulation in the anterior uvea, a measure of Na+, K+-pump activity, was higher than adult values 6 hr after birth (T/M25.2 +/- 0.9). Activity remained elevated through day 28 and did not fall to adult levels until day 60 (T/M 13.4 +/- 0.6). Accumulation studies on isolated ciliary processes were similar to those obtained from anterior uveal tissue. Daily subcutaneous injections of penicillin (300,000 units/kg/day) for 1 week had no effect on anterior uvea PAH accumulation (penicillin T/M was 1.7 +/- 0.1 and saline control T/M was 2.0 +/- 0.2). Accumulation of either /sup 3/H-PAH or /sup 86/Rb+ by the choroid plexus was present 1 day after birth in amounts that were similar to adult values and did not change during the 90 days of testing.

  17. The choroid plexus response to a repeated peripheral inflammatory stimulus

    PubMed Central

    2009-01-01

    Background Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid. Results In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection. Conclusion These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated. PMID:19922669

  18. Studies on the human choroid plexus in vitro.

    PubMed

    Redzic, Zoran B

    2013-01-01

    The role of human choroid plexus (CP) epithelium in the transport of solutes between the blood and the cerebrospinal fluid and/or in secretion processes may be studied by employing several experimental approaches. There are a number of in vitro techniques for human CP epithelium (CPE) and all have limitations that do not exclude them a priori, but that should be carefully taken into consideration. Developmental and morphological studies have been largely performed on human choroid plexus samples of either embryonic or post-mortem origin. Functional uptake studies may be performed on pathologically unaltered CP samples obtained during surgical removal of choroid plexus tumors. This approach can be used to explore transport processes mainly across the apical side of the CPE, but cannot be used to study vectorial transport across the CPE. Also, these samples have limited viability. A monolayer of CPE in culture, grown on permeable supports, provides the best available tool to study transport processes or polarized secretion by the CP, but thus far only limited attempts to culture these cells have been published and they mainly include data from neoplastic CPE. A study that used a human papilloma-derived cell line in culture showed that it forms a monolayer with barrier properties, although the cells express pleomorphic and neoplastic features and lack contact inhibition. Other cell cultures express some CPE markers but do not develop tight junctions/barrier properties. This article reviews the main characteristics and limitations of available in vitro methods to study human CPE, which could help researchers choose an appropriate experimental approach for a particular study. PMID:23391221

  19. Choriocapillaris and Choroidal Microvasculature Imaging with Ultrahigh Speed OCT Angiography

    PubMed Central

    Choi, WooJhon; Mohler, Kathrin J.; Potsaid, Benjamin; Lu, Chen D.; Liu, Jonathan J.; Jayaraman, Vijaysekhar; Cable, Alex E.; Duker, Jay S.; Huber, Robert; Fujimoto, James G.

    2013-01-01

    We demonstrate in vivo choriocapillaris and choroidal microvasculature imaging in normal human subjects using optical coherence tomography (OCT). An ultrahigh speed swept source OCT prototype at 1060 nm wavelengths with a 400 kHz A-scan rate is developed for three-dimensional ultrahigh speed imaging of the posterior eye. OCT angiography is used to image three-dimensional vascular structure without the need for exogenous fluorophores by detecting erythrocyte motion contrast between OCT intensity cross-sectional images acquired rapidly and repeatedly from the same location on the retina. En face OCT angiograms of the choriocapillaris and choroidal vasculature are visualized by acquiring cross-sectional OCT angiograms volumetrically via raster scanning and segmenting the three-dimensional angiographic data at multiple depths below the retinal pigment epithelium (RPE). Fine microvasculature of the choriocapillaris, as well as tightly packed networks of feeding arterioles and draining venules, can be visualized at different en face depths. Panoramic ultra-wide field stitched OCT angiograms of the choriocapillaris spanning ∼32 mm on the retina show distinct vascular structures at different fundus locations. Isolated smaller fields at the central fovea and ∼6 mm nasal to the fovea at the depths of the choriocapillaris and Sattler's layer show vasculature structures consistent with established architectural morphology from histological and electron micrograph corrosion casting studies. Choriocapillaris imaging was performed in eight healthy volunteers with OCT angiograms successfully acquired from all subjects. These results demonstrate the feasibility of ultrahigh speed OCT for in vivo dye-free choriocapillaris and choroidal vasculature imaging, in addition to conventional structural imaging. PMID:24349078

  20. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  1. Current and emerging treatment options for myopic choroidal neovascularization

    PubMed Central

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra

    2015-01-01

    Choroidal neovascularization (CNV) is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. PMID:25987831

  2. Current and emerging treatment options for myopic choroidal neovascularization.

    PubMed

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra

    2015-01-01

    Choroidal neovascularization (CNV) is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. PMID:25987831

  3. Automated choroidal neovascularization detection algorithm for optical coherence tomography angiography

    PubMed Central

    Liu, Li; Gao, Simon S.; Bailey, Steven T.; Huang, David; Li, Dengwang; Jia, Yali

    2015-01-01

    Optical coherence tomography angiography has recently been used to visualize choroidal neovascularization (CNV) in participants with age-related macular degeneration. Identification and quantification of CNV area is important clinically for disease assessment. An automated algorithm for CNV area detection is presented in this article. It relies on denoising and a saliency detection model to overcome issues such as projection artifacts and the heterogeneity of CNV. Qualitative and quantitative evaluations were performed on scans of 7 participants. Results from the algorithm agreed well with manual delineation of CNV area. PMID:26417524

  4. Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma

    PubMed Central

    Béliveau-Nadeau, Dominic; Callejo, Sonia

    2016-01-01

    Radiotherapy has a long history in the organ-sparing management of choroidal melanoma. Joining plaque radiotherapy and proton irradiation, stereotactic robotic photon irradiation is a new tool in the radiation oncologist’s armamentarium for ocular tumors. The non-coplanar fields with steep dose gradients are well suited to spare uninvolved retina, anterior chamber, and the optic nerve. In our practice, it is the preferred treatment for melanomas that are non-amenable to standard plaque brachytherapy. Since late 2010, we have treated more than 40 patients with our robotic linear accelerator. This case-based technical note outlines the technique used at the University of Montreal, Montreal, Canada. PMID:27226942

  5. Visual scoring of non-cavitated caries lesions and clinical trial efficiency, testing xylitol in caries active adults

    PubMed Central

    Brown, JP; Amaechi, BT; Bader, JD; Gilbert, GH; Makhija, SK; Lozano-Pineda, J; Leo, MC; Chuhe, C; Vollmer, WM

    2013-01-01

    Objectives To better understand the effectiveness of xylitol in caries prevention in adults, and to attempt improved clinical trial efficiency. Methods As part of the Xylitol for Adult Caries Trial (X-ACT), non-cavitated and cavitated caries lesions were assessed in subjects who were experiencing the disease. The trial was a test of the effectiveness of 5 grams/day of xylitol, consumed by dissolving in the mouth five 1 gram lozenges spaced across each day, compared with a sucralose placebo. For this analysis, seeking trial efficiency, 538 subjects aged 21–80, with complete data for four dental examinations were selected from the 691 randomized into the three year trial, conducted at three sites. Acceptable inter and intra examiner reliability before and during the trial was quantified using the kappa statistic. Results The mean annualized non-cavitated plus cavitated lesion transition scores in coronal and root surfaces, from sound to carious favoured xylitol over placebo, during the three cumulative periods of 12, 24, and 33 months, but these clinically and statistically non-significant differences declined in magnitude over time. Restricting the present assessment to those subjects with a higher baseline lifetime caries experience showed possible but inconsistent benefit. Conclusions There was no clear and clinically relevant preventive effect of xylitol on caries in adults with adequate fluoride exposure when non-cavitated plus cavitated lesions were assessed. This conformed to the X-ACT trial result assessing cavitated lesions. Including non-cavitated lesion assessment in this full scale, placebo controlled, multi site, randomized, double blinded clinical trial in adults experiencing dental caries, did not achieve added trial efficiency or demonstrate practical benefit of xylitol. Trial Registration ClinicalTrials.Gov NCT00393055 PMID:24205951

  6. Active Breathing Control in Combination With Ultrasound Imaging: A Feasibility Study of Image Guidance in Stereotactic Body Radiation Therapy of Liver Lesions

    SciTech Connect

    Bloemen-van Gurp, Esther; Meer, Skadi van der; Hendry, Janet; Buijsen, Jeroen; Visser, Peter; Fontanarosa, Davide; Lachaine, Martin; Lammering, Guido; Verhaegen, Frank

    2013-03-15

    Purpose: Accurate tumor positioning in stereotactic body radiation therapy (SBRT) of liver lesions is often hampered by motion and setup errors. We combined 3-dimensional ultrasound imaging (3DUS) and active breathing control (ABC) as an image guidance tool. Methods and Materials: We tested 3DUS image guidance in the SBRT treatment of liver lesions for 11 patients with 88 treatment fractions. In 5 patients, 3DUS imaging was combined with ABC. The uncertainties of US scanning and US image segmentation in liver lesions were determined with and without ABC. Results: In free breathing, the intraobserver variations were 1.4 mm in left-right (L-R), 1.6 mm in superior-inferior (S-I), and 1.3 mm anterior-posterior (A-P). and the interobserver variations were 1.6 mm (L-R), 2.8 mm (S-I), and 1.2 mm (A-P). The combined uncertainty of US scanning and matching (inter- and intraobserver) was 4 mm (1 SD). The combined uncertainty when ABC was used reduced by 1.7 mm in the S-I direction. For the L-R and A-P directions, no significant difference was observed. Conclusion: 3DUS imaging for IGRT of liver lesions is feasible, although using anatomic surrogates in the close vicinity of the lesion may be needed. ABC-based breath-hold in midventilation during 3DUS imaging can reduce the uncertainty of US-based 3D table shift correction.

  7. Two-year results of intravitreal ranibizumab for polypoidal choroidal vasculopathy with recurrent or residual exudation

    PubMed Central

    Saito, M; Iida, T; Kano, M; Itagaki, K

    2013-01-01

    Aim To clarify the 2-year efficacy of ranibizumab for patients with polypoidal choroidal vasculopathy (PCV) with recurrent or residual exudation from branching vascular networks after previous photodynamic therapy (PDT). Methods We retrospectively reviewed 26 eyes of 26 Japanese patients (22 men, 4 women) in this pilot study. All eyes had PCV with complete regression of polypoidal lesions resulting from PDT detected by indocyanine green angiography (ICGA), but recurrent or residual leakage from branching vascular networks on fluorescein angiography and evidence of persistent fluid on optical coherence tomography (OCT). Three consecutive intravitreal injections of ranibizumab (0.5 mg/0.05 ml) were administered to all eyes. Results The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) improved significantly from 0.55 at baseline to 0.35 at 12 months (P<0.0001) and 0.43 at 24 months (P=0.0012). The mean increases in the BCVA 12 and 24 months after baseline were 1.95 and 1.23 lines, respectively. The mean central retinal thickness significantly decreased from 295 μm at baseline to 189 μm at 12 months (P<0.0038) and 163 μm at 24 months (P<0.001). The mean numbers of intravitreal ranibizumab (IVR) injections at months 12 and 24, including the initial treatments, were 5.8 and 8.8, respectively. Five (19.2%) eyes had recurrent polypoidal lesions on ICGA at a mean of 15.7 months after baseline. At month 24, OCT showed no exudation in 17 (65.4%) of the 26 eyes. No adverse events developed. Conclusions IVR injections maintained or improved the VA and retinal thickness at 24 months in eyes with PCV with recurrent or residual exudation from branching vascular networks after previous PDT. PMID:23743532

  8. Surgical removal of subfoveal choroidal neovascularization in pathologic myopia: a 12-year follow-up study.

    PubMed

    Hera, R; Chiquet, C; Romanet, J P

    2013-12-01

    The purpose of this study was to review the 12-year visual outcomes of patients who underwent surgical removal for subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia. This retrospective study included 14 patients, with a mean age of 45.8 years, high myopia (>6 D) and classic subfoveal CNV. They were treated with pars plana vitrectomy and surgical removal of CNV. All patients were followed up every 3 months for 2 years, with visual acuity (VA), fundus examination, and fluorescein angiography and then every year for 5 years. Ten patients underwent a final visit with VA and fundus examination after a minimum 12-year follow-up. The main outcome measurement was VA and the secondary outcome measurement was the lesion size. After 12 years of follow-up, the mean VA did not significantly change over time, with a mean gain of 0.22 logMAR at 1 year, and 0.18, 0.12 and 0.05 at 2, 5 and 12 years, respectively. The anatomical evolution was characterized by a significant enlargement of the lesion size at 5 years. This study showed that final VA after surgical treatment with 12 years of follow-up was poor, due to the significant CNV scar enlargement over time. These results should prompt a prospective randomized study of other medical treatments, particularly anti-vascular endothelial growth factor therapy. PMID:23539478

  9. Esophageal Cancer Related Gene-4 Is a Choroid Plexus-Derived Injury Response Gene: Evidence for a Biphasic Response in Early and Late Brain Injury

    PubMed Central

    Podvin, Sonia; Gonzalez, Ana-Maria; Miller, Miles C.; Dang, Xitong; Botfield, Hannah; Donahue, John E.; Kurabi, Arwa; Boissaud-Cooke, Matthew; Rossi, Ryan; Leadbeater, Wendy E.; Johanson, Conrad E.; Coimbra, Raul; Stopa, Edward G.; Eliceiri, Brian P.; Baird, Andrew

    2011-01-01

    By virtue of its ability to regulate the composition of cerebrospinal fluid (CSF), the choroid plexus (CP) is ideally suited to instigate a rapid response to traumatic brain injury (TBI) by producing growth regulatory proteins. For example, Esophageal Cancer Related Gene-4 (Ecrg4) is a tumor suppressor gene that encodes a hormone-like peptide called augurin that is present in large concentrations in CP epithelia (CPe). Because augurin is thought to regulate senescence, neuroprogenitor cell growth and differentiation in the CNS, we evaluated the kinetics of Ecrg4 expression and augurin immunoreactivity in CPe after CNS injury. Adult rats were injured with a penetrating cortical lesion and alterations in augurin immunoreactivity were examined by immunohistochemistry. Ecrg4 gene expression was characterized by in situ hybridization. Cell surface augurin was identified histologically by confocal microscopy and biochemically by sub-cellular fractionation. Both Ecrg4 gene expression and augurin protein levels were decreased 24–72 hrs post-injury but restored to uninjured levels by day 7 post-injury. Protein staining in the supraoptic nucleus of the hypothalamus, used as a control brain region, did not show a decrease of auguin immunoreactivity. Ecrg4 gene expression localized to CPe cells, and augurin protein to the CPe ventricular face. Extracellular cell surface tethering of 14 kDa augurin was confirmed by cell surface fractionation of primary human CPe cells in vitro while a 6–8 kDa fragment of augurin was detected in conditioned media, indicating release from the cell surface by proteolytic processing. In rat CSF however, 14 kDa augurin was detected. We hypothesize the initial release and proteolytic processing of augurin participates in the activation phase of injury while sustained Ecrg4 down-regulation is dysinhibitory during the proliferative phase. Accordingly, augurin would play a constitutive inhibitory function in normal CNS while down regulation of Ecrg4

  10. Analysis of Normal Peripapillary Choroidal Thickness via Spectral Domain Optical Coherence Tomography

    PubMed Central

    Ho, Joseph; Branchini, Lauren; Regatieri, Caio; Krishnan, Chandrasekharan; Fujimoto, James G.; Duker, Jay S.

    2011-01-01

    PURPOSE To analyze the normal peripapillary choroidal thickness utilizing a commercial spectral domain optical coherence tomography (OCT) device and determine the inter-grader reproducibility of this method. DESIGN Retrospective, non-comparative, non-interventional case series. PARTICIPANTS Thirty-six eyes of 36 normal patients seen at the New England Eye Center between April and September 2010. METHODS All patients underwent high-definition scanning with the Cirrus HD-OCT. Two raster scans were obtained per eye, a horizontal and a vertical scan, both of which were centered at the optic nerve. Two independent graders individually measured the choroidal thickness. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500 μm intervals away from the optic nerve in the superior, inferior, nasal and temporal quadrants. Statistical analysis was conducted to compare mean choroidal thicknesses. Inter-grader reproducibility was assessed by intraclass correlation coefficient and Pearson’s correlation coefficient. Average choroidal thickness in each quadrant was compared to retinal nerve fiber layer (RNFL) thickness in their respective quadrants. MAIN OUTCOME MEASURES Peripapillary choroidal thickness, intraclass coefficient, Pearson’s correlation coefficient. RESULTS The peripapillary choroid in the inferior quadrant was significantly thinner compared to all other quadrants (p< 0.001). None of the other quadrants were significantly different from each other in terms of thickness. The inferior peripapillary choroid was significantly thinner compared to all other quadrants at all distances measured away from the optic nerve (p< 0.001). Generally, the peripapillary choroid increases in thickness the farther it was away from the optic nerve and eventually approaching a plateau. Intraclass correlation coefficient ranged from 0.62 to 0.93 and Pearson’s correlation coefficient ranged from 0.74 to 0.95 (p

  11. Decreased choroidal thickness in eyes with secondary angle closure glaucoma. An aetiological factor for deep retinal changes in glaucoma?

    PubMed Central

    Kubota, T.; Jonas, J. B.; Naumann, G. O.

    1993-01-01

    A decreased count of retinal photoreceptors all over the fundus and a loss of retinal pigment epithelium cells mainly in the parapapillary region have been reported to be associated with glaucoma. This study addressed the question whether this cell loss in the deep retinal layers may be connected with a change of the choroidal thickness in glaucomatous eyes. Histological sections of 12 eyes with secondary angle closure glaucoma due to a malignant melanoma of the ciliary body and 20 eyes with a malignant choroidal melanoma and normal intraocular pressure were histomorphometrically evaluated. Before enucleation the intraocular pressure was significantly higher in the glaucoma group compared with the control group. Thickness of the choroid was measured at 12 locations from the posterior pole to the fundus periphery. The choroid was significantly thinner in the glaucoma group than in the control group. The decreased choroidal thickness was mainly due to a diminished choroidal vessel diameter. The differences were more marked at the optic disc border than in the fundus periphery. The decreased choroidal thickness in the glaucomatous eyes suggests a reduced choroidal perfusion. It fits with the reported lack of autoregulation of the choroidal blood circulation. Considering the diminished choroidal thickness especially in the parapapillary region, it may be one among other factors explaining the changes of the deep retinal layers in eyes with glaucoma. It indicates that thinning of the choroid, besides the chorioretinal atrophy in the parapapillary region, should be added to the panoply of histological changes in glaucoma. Images PMID:8343472

  12. HTRA1 promoter variant differentiates polypoidal choroidal vasculopathy from exudative age-related macular degeneration

    PubMed Central

    Ng, Tsz Kin; Liang, Xiao Ying; Lai, Timothy Y. Y.; Ma, Li; Tam, Pancy O. S.; Wang, Jian Xiong; Chen, Li Jia; Chen, Haoyu; Pang, Chi Pui

    2016-01-01

    Exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) share similar abnormal choroidal vasculature, but responses to treatments are different. In this study, we sequenced the whole HTRA1 gene and its promoter by direct sequencing in a Hong Kong Chinese PCV cohort. We identified rs11200638, c.34delCinsTCCT, c.59C>T, rs1049331 and rs2293870 significantly associated with PCV. Notably, rs2672598 was significantly associated with exudative AMD (p = 1.31 × 10−4) than PCV (p = 0.11). Logistic regression indicated that rs2672598 (p = 2.27 × 10−3) remained significant after adjusting for rs11200638 in exudative AMD. Moreover, the rs11200638-rs2672598 joint genotype AA-CC conferred higher risk to exudative AMD (43.11 folds) than PCV (3.68 folds). Promoter analysis showed that rs2672598 C-allele showed higher luciferase expression than wildtype T-allele (p = 0.026), independent of rs11200638 genotype (p = 0.621). Coherently, vitreous humor HTRA1 expression with rs2672598 CC genotype was significantly higher than that with TT genotype by 2.56 folds (p = 0.02). Furthermore, rs2672598 C-allele was predicted to alter the transcription factor binding sites, but not rs11200638 A-allele. Our results revealed that HTRA1 rs2672598 is more significantly associated with exudative AMD than PCV in ARMS2/HTRA1 region, and it is responsible for elevated HTRA1 transcriptional activity and HTRA1 protein expression. PMID:27338780

  13. HTRA1 promoter variant differentiates polypoidal choroidal vasculopathy from exudative age-related macular degeneration.

    PubMed

    Ng, Tsz Kin; Liang, Xiao Ying; Lai, Timothy Y Y; Ma, Li; Tam, Pancy O S; Wang, Jian Xiong; Chen, Li Jia; Chen, Haoyu; Pang, Chi Pui

    2016-01-01

    Exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) share similar abnormal choroidal vasculature, but responses to treatments are different. In this study, we sequenced the whole HTRA1 gene and its promoter by direct sequencing in a Hong Kong Chinese PCV cohort. We identified rs11200638, c.34delCinsTCCT, c.59C>T, rs1049331 and rs2293870 significantly associated with PCV. Notably, rs2672598 was significantly associated with exudative AMD (p = 1.31 × 10(-4)) than PCV (p = 0.11). Logistic regression indicated that rs2672598 (p = 2.27 × 10(-3)) remained significant after adjusting for rs11200638 in exudative AMD. Moreover, the rs11200638-rs2672598 joint genotype AA-CC conferred higher risk to exudative AMD (43.11 folds) than PCV (3.68 folds). Promoter analysis showed that rs2672598 C-allele showed higher luciferase expression than wildtype T-allele (p = 0.026), independent of rs11200638 genotype (p = 0.621). Coherently, vitreous humor HTRA1 expression with rs2672598 CC genotype was significantly higher than that with TT genotype by 2.56 folds (p = 0.02). Furthermore, rs2672598 C-allele was predicted to alter the transcription factor binding sites, but not rs11200638 A-allele. Our results revealed that HTRA1 rs2672598 is more significantly associated with exudative AMD than PCV in ARMS2/HTRA1 region, and it is responsible for elevated HTRA1 transcriptional activity and HTRA1 protein expression. PMID:27338780

  14. Regulation of Tumor Angiogenesis and Choroidal Neovascularization by Endogenous Angioinhibitors

    PubMed Central

    Gunda, Venugopal; Sudhakar, Yakkanti A

    2014-01-01

    Angiogenesis is the process of neovascularization from parent blood vessels, which is a prerequisite for many physiological and pathological conditions and is regulated by a balance between endogenous angioinhibitors and angioactivators or angiogenic factors. Imbalance between angioinhibitors and angioactivators is associated with neovascularization capacity during progression of tumor development and Choroidal Neovascularization (CNV). Normalization of pathological angiogenesis is considered as an alternative strategy to prevent the tumor growth in cancer progression or retinal damage in CNV. Various angioinhibitors are being identified and evaluated for their pathological angiogenesis regulation, of which endogenous angioinhibitors are one class derived either from extra cellular matrix or from non-extra cellular matrix of human origin. Endogenous angioinhibitors are gaining much significance as they interact with proliferating endothelial cells by binding to distinct integrins and non-integrin receptors, regulating different intracellular signaling mechanisms leading to inhibition of choroidal neovascularization and tumor growth. This review will focus on endogenous angioinhibitors and their receptor(s) mediated angioinhibitory signaling, which are of major concern in angiogenesis and their clinical and pharmaceutical implications. PMID:25258675

  15. An Angiogenic Role for Adrenomedullin in Choroidal Neovascularization

    PubMed Central

    Sakimoto, Susumu; Kidoya, Hiroyasu; Kamei, Motohiro; Naito, Hisamichi; Yamakawa, Daishi; Sakaguchi, Hirokazu; Wakabayashi, Taku; Nishida, Kohji; Takakura, Nobuyuki

    2013-01-01

    Purpose Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45− endothelial cells (ECs) than CD31−CD45− non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22–52). Intravitreous injection of ADM (22–52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. PMID:23520487

  16. Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA

    PubMed Central

    Kamisah, Yusof; Chua, Kien Hui; Qodriyah, Hj Mohd Saad

    2013-01-01

    The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20 mg/kg) or tocotrienol (60 mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2 content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA. PMID:23970937

  17. Subjects with Higher Physical Activity Levels Have More Severe Focal Knee lesions diagnosed with 3T MRI: Analysis of a Non Symptomatic Cohort of the Osteoarthritis Initiative

    PubMed Central

    Stehling, Christoph; Lane, Nancy E.; Nevitt, Michael C.; Lynch, John; McCulloch, Charles E.; Link, Thomas M.

    2016-01-01

    Purpose To study the prevalence of focal knee abnormalities using 3 Tesla (T) MR studies in relation to physical activity levels in asymptomatic, middle-aged subjects from the Osteoarthritis Initiative (OAI). Material and Methods We analyzed baseline data from 236 45–55 years old individuals (136 women, 100 men) without knee pain (based on WOMAC scores) and a BMI of 19–27 kg/m2. Physical activity levels were determined in all subjects using the Physical Activity Scale for the Elderly (PASE). MRI at 3T was performed using coronal intermediate-weighted (IW) 2D fast spin-echo (FSE), sagittal 3D dual-echo in steady state (DESS) and 2D IW fat-suppressed (fs) FSE sequences of the right knee. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous and other knee abnormalities using the WORMS MRI OA scoring method. Statistical significances between subjects with different activity levels were determined using one-way analysis of variance (ANOVA), chi-square tests and a multivariate regression model adjusted for gender, age, BMI, KL-Score and OA risk factors. Results Meniscal lesions were found in 47% of the 236 subjects, cartilage lesions in 74.6%, bone marrow edema pattern (BMEP) in 40.3% and ligament lesions in 17%. Stratification of subjects by physical activity resulted in an increasing incidence of cartilage, meniscus and ligament abnormalities, BMEP and joint effusion according to activity levels (PASE). The severity grade of cartilage lesions was also associated with PASE levels and presence of other knee abnormalities was also significantly associated with cartilage defects. Conclusion Asymptomatic middle-aged individuals from the OAI incidence cohort had a high prevalence of knee abnormalities; more physically active individuals had significantly more and more severe knee abnormalities independently of gender, age, BMI, KL-Score and OA risk factors. This data therefore also suggests that subjects

  18. Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia

    PubMed Central

    Chen, Wei; Guan, Yubo; He, Guanghui; Li, Zhiwei; Song, Hui; Xie, Shiyong; Han, Quanhong

    2015-01-01

    Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV). Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography. Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P < 0.001) and control (P < 0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P < 0.001) group. A statistically significant difference (P = 0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P = 0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups. Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV. PMID:26491554

  19. The p75 neurotrophin receptor localization in blood-CSF barrier: expression in choroid plexus epithelium

    PubMed Central

    2011-01-01

    Background The presence of neurotrophins and their receptors Trk family has been reported in the choroid plexus. High levels of Nerve Growth Factor (NGF), Neurotrophin-4 (NT-4) and TrkB receptor were detected, while nothing was know about p75 neurotrophin receptor (p75NTR) in the choroid plexus epithelial cells. In neurons, p75NTR receptor has a dual function: promoting survival together with TrkA in response to NGF, and inducing apoptotic signaling through p75NTR. We postulated that p75NTR may also affect the survival pathways in the choroid plexus and also undergoes regulated proteolysis with metalloproteases. Results Here, we demonstrated the presence of p75NTR receptor in the choroid plexus epithelial cells. The p75NTR receptor would be involved in cell death mechanisms and in the damaged induced by amyloid beta (Aβ) in the choroid plexus and finally, we propose an essential role of p75NTR in the Aβ transcytosis through out choroid plexus barrier. Conclusions The presence analysis reveals the new localization of p75NTR in the choroid plexus and, the distribution mainly in the cytoplasm and cerebrospinal fluid (CSF) side of the epithelial cells. We propose that p75NTR receptor plays a role in the survival pathways and Aβ-induced cell death. These data suggest that p75NTR dysfunction play an important role in the pathogenesis of brain diseases. The importance and novelty of this expression expands a new role of p75NTR. PMID:21569322

  20. CHOROIDAL THICKNESS IN PATIENTS WITH DIABETIC RETINOPATHY ANALYZED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY

    PubMed Central

    REGATIERI, CAIO V.; BRANCHINI, LAUREN; CARMODY, JILL; FUJIMOTO, JAMES G.; DUKER, JAY S.

    2012-01-01

    Purpose This study was designed to examine choroidal thickness in patients with diabetes using spectral-domain optical coherence tomography. Methods Forty-nine patients (49 eyes) with diabetes and 24 age-matched normal subjects underwent high-definition raster scanning using spectral-domain optical coherence tomography with frame enhancement software. Patients with diabetes were classified into 3 groups: 11 patients with mild or moderate nonproliferative diabetic retinopathy and no macular edema, 18 patients with nonproliferative diabetic retinopathy and diabetic macular edema, and 20 patients with treated proliferative diabetic retinopathy and no diabetic macular edema (treated proliferative diabetic retinopathy). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-μm intervals up to 2,500 μm temporal and nasal to the fovea. Results Reliable measurements of choroidal thickness were obtainable in 75.3% of eyes examined. Mean choroidal thickness showed a pattern of thinnest choroid nasally, thickening in the subfoveal region, and thinning again temporally in normal subjects and patients with diabetes. Mean subfoveal choroidal thickness was thinner in patients with diabetic macular edema (63.3 μm, 27.2%, P < 0.05) or treated proliferative diabetic retinopathy (69.6 μm, 30.0%, P < 0.01), compared with normal subjects. There was no difference between nonproliferative diabetic retinopathy and normal subjects. Conclusion Choroidal thickness is altered in diabetes and may be related to the severity of retinopathy. Presence of diabetic macular edema is associated with a significant decrease in the choroidal thickness. PMID:22374157

  1. Novel method using 3-dimensional segmentation in spectral domain-optical coherence tomography imaging in the chick reveals defocus-induced regional and time-sensitive asymmetries in the choroidal thickness.

    PubMed

    Nava, Diane R; Antony, Bhavna; Zhang, L I; Abràmoff, Michael D; Wildsoet, Christine F

    2016-01-01

    Studies into the mechanisms underlying the active emmetropization process by which neonatal refractive errors are corrected, have described rapid, compensatory changes in the thickness of the choroidal layer in response to imposed optical defocus. While high frequency A-scan ultrasonography, as traditionally used to characterize such changes, offers good resolution of central (on-axis) changes, evidence of local retinal control mechanisms make it imperative that more peripheral, off-axis changes also be tracked. In this study, we used in vivo high resolution spectral domain-optical coherence tomography (SD-OCT) imaging in combination with the Iowa Reference Algorithms for 3-dimensional segmentation, to more fully characterize these changes, both spatially and temporally, in young, 7-day old chicks (n = 15), which were fitted with monocular +15 D defocusing lenses to induce choroidal thickening. With these tools, we were also able to localize the retinal area centralis, which was used as a landmark along with the ocular pectin in standardizing the location of scans and aligning them for subsequent analyses of choroidal thickness (CT) changes across time and between eyes. Values were derived for each of four quadrants, centered on the area centralis, and global CT values were also derived for all eyes. Data were compared with on-axis changes measured using ultrasonography. There were significant on-axis choroidal thickening that was detected after just one day of lens wear (∼190 µm), and regional (quadrant-related) differences in choroidal responses were also found, as well as global thickness changes 1 day after treatment. The ratio of global to on-axis choroidal thicknesses, used as an index of regional variability in responses, was also found to change significantly, reflecting the significant central changes. In summary, we demonstrated in vivo high resolution SD-OCT imaging, used in combination with segmentation algorithms, to be a viable and informative

  2. Photodynamic therapy for diffuse choroidal hemangioma in a child with Sturge-Weber syndrome.

    PubMed

    Nugent, Ryan; Lee, Lawrence; Kwan, Anthony

    2015-04-01

    Sturge-Weber syndrome is a rare neurocutaneous disorder involving the leptomeninges, skin of the face, and, in 40% of cases, diffuse choroidal hemangioma. We report the case of a 6-year-old girl with Sturge-Weber syndrome and a large diffuse choroidal hemangioma with retinal detachment involving the majority of the retina. The patient underwent photodynamic therapy. The retinal detachment resolved completely within 3 months of treatment. This case represents the youngest patient in the literature to undergo successful treatment with photodynamic therapy for Sturge-Weber syndrome-associated diffuse choroidal hemangioma. PMID:25828818

  3. Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus

    SciTech Connect

    Muccioli, G.; Guardabassi, A.; Pattono, P. )

    1990-03-01

    The occurrence of prolactin binding sites in some brain structures (telencephalon, ventral hypothalamus, myelencephalon, hypophysis, and choroid plexus) from Xenopus laevis (anuran amphibian) was studied by the in vitro biochemical technique. The higher binding values were obtained at the level of the choroid plexus and above all of the hypothalamus. On the bases of hormonal specificity and high affinity, these binding sites are very similar to those of prolactin receptors of classical target tissues as well as of those described by us in other structures from Xenopus. To our knowledge, the present results provide the first demonstration of the occurrence of prolactin specific binding sites in Xenopus laevis choroid plexus cells.

  4. [The use of aflibercept (Eylea) in the treatment of polypoidal choroidal vasculopathy--case report].

    PubMed

    Glasner, Paulina; Raczyńska, Dorota; Glasner, Leopold

    2015-01-01

    The paper presents a case of a 25-year-old woman referred to the Outpatient Clinic at the Department of Ophthalmology, University Clinical Centre in Gdansk, with sudden vision impairment in her right eye. Clinical manifestation and diagnostic tests gave a basis for the preliminary diagnosis of polypoidal choroidal vasculopathy. Polypoidal choroidal vasculopathy is a type of choroidal neovascularisation, frequently confused with age-related macular degeneration. Standard treatment includes photodynamic therapy and intravitreal injections of anti-vascular endothelial growth factor agents. 2.0 miligrams of aflibercept was administered as an intravitreal injection, causing a rapid, significant improvement of visual function and proper anatomical relationships within the retina. PMID:26999944

  5. Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

    PubMed

    Wing, Ana Cristina; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Sacramento, Priscila M; Andrade, Regis M; Camargo, Solange; Rueda, Fernanda; Alves-Leon, Soniza V; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-02-01

    Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis. PMID:26781085

  6. IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment.

    PubMed

    Gaddipati, Subhash; Lu, Qingxian; Kasetti, Ramesh Babu; Miller, M Clarke; Lu, Qingjun; Trent, John O; Kaplan, Henry J; Li, Qiutang

    2015-01-01

    The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 ¼m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retrobulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR) tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of TPCA-1 delivered

  7. Evaluation of anti-ulcer activity of Samanea saman (Jacq) merr bark on ethanol and stress induced gastric lesions in albino rats

    PubMed Central

    Arumugam, Suresh; Selvaraj, Senthil Velan; Velayutham, Suresh; Natesan, Senthil Kumar; Palaniswamy, Karthikeyan

    2011-01-01

    Objective: To evaluate the antiulcer activity of Samanea saman (Jacq) Merr bark on ethanol and stress induced gastric lesions in albino rats. Materials and Methods: Gastric lesions were induced in rats by oral administration of absolute ethanol (5 ml/kg) and stress induced by water immersion. The antiulcer activity of methanolic extract of Samanea saman (Jacq) Merr bark (100 mg/kg, 200 mg/kg, 400 mg/kg) was compared with standard drugs. The parameters studied were ulcer index, gastric juice volume, pH, free acidity and total acidity. Result: Samanea saman (Jacq) Merr showed a dose dependent curative ratio compared to ulcer control groups. The extract at 400 mg/kg showed significant anti ulcer activity which is almost equal to that of the standard drug in both models. The volume of acid secretion, total and free acidity was decreased and pH of the gastric juice was increased compared to ulcer control group. Conclusions: The present study indicates that Samanea saman (Jacq) Merr bark extracts have potential anti ulcer activity. PMID:22022006

  8. Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.

    PubMed

    Lee, Bang-Ning; Follen, Michele; Shen, De-Yu; Malpica, Anais; Adler-Storthz, Karen; Shearer, William T; Reuben, James M

    2004-03-01

    Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells. PMID:15013969

  9. Effect of glatiramer acetate three-times weekly on the evolution of new, active multiple sclerosis lesions into T1-hypointense "black holes": a post hoc magnetic resonance imaging analysis.

    PubMed

    Zivadinov, Robert; Dwyer, Michael; Barkay, Hadas; Steinerman, Joshua R; Knappertz, Volker; Khan, Omar

    2015-03-01

    Conversion of active lesions to black holes has been associated with disability progression in subjects with relapsing-remitting multiple sclerosis (RRMS) and represents a complementary approach to evaluating clinical efficacy. The objective of this study was to assess the conversion of new active magnetic resonance imaging (MRI) lesions, identified 6 months after initiating treatment with glatiramer acetate 40 mg/mL three-times weekly (GA40) or placebo, to T1-hypointense black holes in subjects with RRMS. Subjects received GA40 (n = 943) or placebo (n = 461) for 12 months. MRI was obtained at baseline and Months 6 and 12. New lesions were defined as either gadolinium-enhancing T1 or new T2 lesions at Month 6 that were not present at baseline. The adjusted mean numbers of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a negative binomial model; adjusted proportions of new active lesions at Month 6 converting to black holes at Month 12 were analyzed using a logistic regression model. Of 1,292 subjects with complete MRI data, 433 (50.3 %) GA-treated and 247 (57.2 %) placebo-treated subjects developed new lesions at Month 6. Compared with placebo, GA40 significantly reduced the mean number (0.31 versus 0.45; P = .0258) and proportion (15.8 versus 19.6 %; P = .006) of new lesions converting to black holes. GA significantly reduced conversion of new active lesions to black holes, highlighting the ability of GA40 to prevent tissue damage in RRMS. PMID:25542295

  10. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  11. Radiotherapy for choroidal melanoma. An 18-year experience with radon

    SciTech Connect

    Davidorf, F.H.; Pajka, J.T.; Makley, T.A. Jr.; Kartha, M.K.

    1987-03-01

    Twenty-three patients were treated with radon therapy for choroidal melanoma at the Ohio State University Hospitals, Columbus, between 1968 and 1976. We present an 18-year experience, including follow-up of at least eight years, in all those receiving therapy. Three patients (13%) died of metastatic disease. Four patients (17.4%) died of other causes. Sixteen patients (69.6%) were alive, with no signs of metastatic disease. Eight patients subsequently required enucleation due to inadequate tumor response. Of the 15 patients who demonstrated successful tumor destruction and retained their eyes, 13 (86.7%) developed substantial irradiation-induced retinopathy, including hard exudates, telangiectasias, neovascularization, microaneurysms, intraretinal and vitreous hemorrhages, secondary glaucoma, and irradiation-induced cataract. Our long-term results indicate a high incidence of both vascular complications and decreased visual acuity.

  12. Choroidal Neovascularization Secondary to Myopia, Infection and Inflammation.

    PubMed

    Weber, Marissa L; Heier, Jeffrey S

    2016-01-01

    Choroidal neovascularization (CNV) is a significant cause of vision loss in all age groups. The most common cause of CNV is age-related macular degeneration (AMD). However, CNV can also occur as a secondary manifestation of various inherited and acquired conditions, including pathologic myopia, presumed ocular histoplasmosis syndrome, angioid streaks, and various hereditary, traumatic or inflammatory disorders. Fluorescein angiography and optical coherence tomography are useful tools in the diagnosis and evaluation of CNV. Treatment options are similar to those for CNV secondary to AMD, specifically anti-angiogenic therapy, but including laser photocoagulation, photodynamic therapy and surgery. Anti-angiogenic therapy has been associated with better visual outcomes than other treatment modalities and is now advocated as the first-line therapy for CNV secondary to myopia, infection and inflammation. PMID:26501802

  13. Nonsurgical management of periapical lesions

    PubMed Central

    Fernandes, Marina; de Ataide, Ida

    2010-01-01

    Periapical lesions develop as sequelae to pulp disease. They often occur without any episode of acute pain and are discovered on routine radiographic examination. The incidence of cysts within periapical lesions varies between 6 and 55%. The occurrence of periapical granulomas ranges between 9.3 and 87.1%, and of abscesses between 28.7 and 70.07%. It is accepted that all inflammatory periapical lesions should be initially treated with conservative nonsurgical procedures. Studies have reported a success rate of up to 85% after endodontic treatment of teeth with periapical lesions. A review of literature was performed by using electronic and hand searching methods for the nonsurgical management of periapical lesions. Various methods can be used in the nonsurgical management of periapical lesions: the conservative root canal treatment, decompression technique, active nonsurgical decompression technique, aspiration-irrigation technique, method using calcium hydroxide, Lesion Sterilization and Repair Therapy, and the Apexum procedure. Monitoring the healing of periapical lesions is essential through periodic follow-up examinations. PMID:21217952

  14. IKK2 Inhibition Attenuates Laser-Induced Choroidal Neovascularization

    PubMed Central

    Lu, Huayi; Lu, Qingxian; Gaddipati, Subhash; Kasetti, Ramesh Babu; Wang, Wei; Pasparakis, Manolis; Kaplan, Henry J.; Li, Qiutang

    2014-01-01

    Choroidal neovascularization (CNV) is aberrant angiogenesis associated with exudative age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Inflammation has been suggested as a risk factor for AMD. The IKK2/NF-κB pathway plays a key role in the inflammatory response through regulation of the transcription of cytokines, chemokines, growth factors and angiogenic factors. We investigated the functional role of IKK2 in development of the laser-induced CNV using either Ikk2 conditional knockout mice or an IKK2 inhibitor. The retinal neuronal tissue and RPE deletion of IKK2 was generated by breeding Ikk2−/flox mice with Nestin-Cre mice. Deletion of Ikk2 in the retina caused no obvious defect in retinal development or function, but resulted in a significant reduction in laser-induced CNV. In addition, intravitreal or retrobulbar injection of an IKK2 specific chemical inhibitor, TPCA-1, also showed similar inhibition of CNV. Furthermore, in vitro inhibition of IKK2 in ARPE-19 cells significantly reduced heat shock-induced expression of NFKBIA, IL1B, CCL2, VEGFA, PDGFA, HIF1A, and MMP-2, suggesting that IKK2 may regulate multiple molecular pathways involved in laser-induced CNV. The in vivo laser-induced expression of VEGFA, and HIF1A in RPE and choroidal tissue was also blocked by TPCA-1 treatment. Thus, IKK2/NF-κB signaling appears responsible for production of pro-inflammatory and pro-angiogenic factors in laser-induced CNV, suggesting that this intracellular pathway may serve as an important therapeutic target for aberrant angiogenesis in exudative AMD. PMID:24489934

  15. Evaluation of choroidal thickness changes after phacoemulsification surgery

    PubMed Central

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Muhafiz, Ersin; Kırboğa, Kadir; Gürdal, Canan

    2016-01-01

    Purpose The aim of the study was to analyze the effects of uneventful phacoemulsification surgery on choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT). Methods In this prospective study, 38 eyes of 38 patients having phacoemulsification surgery were included. All patients underwent detailed ophthalmologic examination, including preoperative axial length (AXL) measurement with optical biometry and intraocular pressure (IOP) measurement preoperatively and 1 month postoperatively. The CT was measured perpendicularly at the fovea and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal using SD-OCT preoperatively and 1 month postoperatively. Changes in the CT after surgery and correlation of this change with age, AXL, preoperative IOP, and IOP change were evaluated. Results There was a statistically significant increase in the CT at all regions evaluated. This increment was more prominent in the nasal and subfoveal regions. The IOP decreased significantly 1 month after surgery (16.14±4.94 mmHg vs 13.91±4.86 mmHg; P<0.001). The change in IOP was correlated with the CT changes at all regions, whereas age, AXL, and preoperative IOP had no significant correlations with the changes in CT. Conclusion Phacoemulsification surgery may cause significant increase in CT, which is correlated with surgery-induced IOP change in the short term. Long-term follow-up of eyes having phacoemulsification surgery may provide further insight into the effects of cataract surgery on the choroid. PMID:27307699

  16. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia

    PubMed Central

    Al-Zahrani, Yahya A.; Al-Dhibi, Hassan A.; Al-Abdullah, Abdulelah A.

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  17. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia.

    PubMed

    Al-Zahrani, Yahya A; Al-Dhibi, Hassan A; Al-Abdullah, Abdulelah A

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid. PMID:26957857

  18. Identification of RALDH2 as a Visually Regulated Retinoic Acid Synthesizing Enzyme in the Chick Choroid

    PubMed Central

    Hollaway, Lindsey R.; Lam, Wengtse; Li, Nan; Napoli, Joseph L.

    2012-01-01

    Purpose. All-trans-retinoic acid (atRA) has been implicated in the local regulation of scleral proteoglycan synthesis in vivo. The purpose of the present study was to identify the enzymes involved in the synthesis of atRA during visually guided ocular growth, the cells involved in modulation of atRA biosynthesis in the choroid, and the effect of choroid-derived atRA on scleral proteoglycan synthesis. Methods. Myopia was induced in White leghorn chicks by form deprivation for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of atRA synthesizing enzymes was evaluated by semiquantitative qRT-PCR, in situ hybridization, and immunohistochemistry. atRA synthesis was measured in organ cultures of isolated choroids using LC-tandem MS quantification. Scleral proteoglycan synthesis was measured in vitro by the incorporation of 35SO4 in CPC-precipitable glycosaminoglycans. Results. RALDH2 was the predominant RALDH transcript in the choroid (>100-fold that of RALDH3). RALDH2 mRNA was elevated after 12 and 24 hours of recovery (60% and 188%, respectively; P < 0.01). The atRA concentration was significantly higher in cultures of choroids from 24-hour to 15-day recovering eyes than in paired controls (∼195%; P < 0.01). Choroid conditioned medium from recovering choroids inhibited proteoglycan synthesis to 43% of controls (P < 0.02, paired t-test; n = 16) and produced a relative inhibition corresponding to a RA concentration of 7.20 × 10−8 M. Conclusions. The results of this study suggest that RALDH2 is the major retinal dehydrogenase in the chick choroid and is responsible for increased atRA synthesis in response to myopic defocus. PMID:22323456

  19. Localized choroidal thickness variation and pigment epithelial detachment in dome-shaped macula with subretinal fluid.

    PubMed

    Deobhakta, Avnish; Ross, Adam H; Helal, John; Maia, André; Freund, K Bailey

    2015-03-01

    The objective of this report is to demonstrate that individuals with dome-shaped macula can develop persistent subretinal fluid due to abrupt changes in the thickness of the choroid, making it unlikely to be reported. Additionally, these patients often have pigment epithelial detachments, suggestive of possible choroidal neo-vascularization. These two qualities can often lead to persistent subretinal fluid that is refractory to treatment. PMID:25835309

  20. Association between choroidal thickness and anterior chamber segment in eyes with narrow or open-angle

    PubMed Central

    Li, Song-Feng; Wu, Ge-Wei; Chen, Chang-Xi; Shen, Ling; Zhang, Zhi-Bao; Gao, Fei; Wang, Ning-Li

    2016-01-01

    AIM To investigate the relationship between choroidal thickness and anterior chamber segment in subjects with eyes with narrow or open-angle. METHODS The subfoveal choroidal thickness was measured with enhanced depth-imaging optical coherence tomography and anterior chamber parameters were measured with ultrasound biomicroscopy in one eye of 23 subjects with open-angle eyes and 38 subjects with narrow-angle eyes. The mean age was 59.52±7.04y for narrow-angle subjects and 60.76±7.23y for open-angle subjects (P=0.514). Multivariate linear regression analysis was performed to assess the association between choroidal thickness and narrow-angle parameters. RESULTS There were no differences in subfoveal choroidal thickness between open- and narrow-angle subjects (P=0.231). Anterior chamber parameters, including central anterior chamber depth, trabecular iris angle, iris thickness 500 µm from the scleral spur (IT500), and ciliary body thickness at 1 mm and 2 mm from the scleral spur (CBT1, CBT2) showed significant differences between the two groups (P<0.05). Subfoveal choroidal thickness showed negative correlation (β=-0.496, P=0.016) only with anterior chamber depth in the open-angle group and with age (β=-0.442, P=0.003) and IT500 (β=-0.399, P=0.008) in the narrow-angle group. However, subfoveal choroidal thickness was not correlated with trabecular iris angle, anterior chamber depth, ciliary body thickness, or central corneal thickness in the narrow-angle group. CONCLUSION Choroidal thickness does not differ in the two groups and has not correlated with anterior chamber parameters in narrow-angle subjects, suggesting a lack of relationship between choroidal thickness and primary angle-closure glaucoma. PMID:27588269

  1. The Phosphoenolpyruvate Phosphotransferase System in Group A Streptococcus Acts To Reduce Streptolysin S Activity and Lesion Severity during Soft Tissue Infection

    PubMed Central

    Gera, Kanika; Le, Tuquynh; Jamin, Rebecca; Eichenbaum, Zehava

    2014-01-01

    Obtaining essential nutrients, such as carbohydrates, is an important process for bacterial pathogens to successfully colonize host tissues. The phosphoenolpyruvate phosphotransferase system (PTS) is the primary mechanism by which bacteria transport sugars and sense the carbon state of the cell. The group A streptococcus (GAS) is a fastidious microorganism that has adapted to a variety of niches in the human body to elicit a wide array of diseases. A ΔptsI mutant (enzyme I [EI] deficient) generated in three different strains of M1T1 GAS was unable to grow on multiple carbon sources (PTS and non-PTS). Complementation with ptsI expressed under its native promoter in single copy was able to rescue the growth defect of the mutant. In a mouse model of GAS soft tissue infection, all ΔptsI mutants exhibited a significantly larger and more severe ulcerative lesion than mice infected with the wild type. Increased transcript levels of sagA and streptolysin S (SLS) activity during exponential-phase growth was observed. We hypothesized that early onset of SLS activity would correlate with the severity of the lesions induced by the ΔptsI mutant. In fact, infection of mice with a ΔptsI sagB double mutant resulted in a lesion comparable to that of either the wild type or a sagB mutant alone. Therefore, a functional PTS is not required for subcutaneous skin infection in mice; however, it does play a role in coordinating virulence factor expression and disease progression. PMID:24379283

  2. Expression of connexin 43 and E-cadherin in choroidal melanoma

    PubMed Central

    Mou, Ying-Ying; Zhao, Gui-Qiu; Lin, Jin-Yong; Zhao, Jie; Lin, Hong; Hu, Li-Ting; Xu, Qiang; Wang 1, Qing; Sun, Wei-Rong

    2011-01-01

    AIM To investigate the expression of connexin 43 and epithelial cadherin (E-cadherin) in choroidal melanoma, to explore the clinical and pathological implications of expression of these proteins, and to determine their relations with malignant features. METHODS The expression of connexin 43 and E-cadherin in choroidal melanoma were detected by immunohistochemistry and correlated with clinicopathological features. RESULTS Positive rates of connexin 43 in choroidal melanomas and benign pigmented nevus tissues were 75% and 40% respectively with significant differences between the two groups (χ2=5.607, P=0.009). Positive rates of E-cadherin in choroidal melanomas and benign pigmented nevus tissues were 40% and 75% respectively with significant differences between the two groups (χ2=5.214, P=0.010). Significant overexpression of connexin 43 and reduction of E-cadherin expression was associated with the invasion to the sclera, and there were respectively significant differences between without and with scleral invasion groups (χ2=2.880, P=0.040; χ2=2.778, P=0.046). Overexpression of connexin 43 were correlated with tumor cell types and the expression of connexin 43 and E-cadherin may be correlated with each other. CONCLUSION The increased expression of connexin 43 and the decreased expression of E-cadherin may be involved in the process of invasion of choroidal melanoma. The overepression of connexin 43 and reduction of E-cadherin may contribute to the development of choroidal melanoma. PMID:22553632

  3. Investigating the choriocapillaris and choroidal vasculature with new optical coherence tomography technologies.

    PubMed

    Ferrara, Daniela; Waheed, Nadia K; Duker, Jay S

    2016-05-01

    The body of knowledge of in vivo investigation of the choroid has been markedly enhanced by recent technological advances in optical coherence tomography (OCT). New insights elucidating the morphological features of the choriocapillaris and choroidal vasculature, in both physiological and pathological conditions, indicate that the choroid plays a pivotal role in many posterior segment diseases. In this article, a review of the histological characteristics of the choroid, which must be considered for the proper interpretation of in vivo imaging, is followed by a comprehensive discussion of fundamental principles of the current state-of-the-art in OCT, including cross-sectional OCT, en face OCT, and OCT angiography using both spectral domain OCT and swept source OCT technologies. A detailed review of the tomographic features of the choroid in the normal eye is followed by relevant findings in prevalent chorioretinal diseases, focusing on major causes of vision loss such as typical early and advanced age-related macular degeneration, polypoidal choroidal vasculopathy, central serous chorioretinopathy, pachychoroid spectrum disorders, diabetic choroidopathy, and myopia. PMID:26478514

  4. Evaluation of Choroidal Thickness in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

    PubMed Central

    Ozec, Ayse Vural; Dogan, Oznur; Dursun, Feyza Gulac; Toker, Mustafa Ilker; Topalkara, Aysen; Arici, Mustafa Kemal; Erdogan, Haydar

    2016-01-01

    Purpose. To compare the macular and peripapillary choroidal thickness in eyes with pseudoexfoliation (PEX) syndrome and PEX glaucoma with the normal eyes of healthy controls. Materials and Methods. In this prospective study, 30 eyes of 30 patients with PEX syndrome, 28 eyes of 28 patients with PEX glaucoma, and 30 eyes of 30 age-matched healthy subjects were enrolled. Choroidal thicknesses in the macular and peripapillary areas were measured by using spectral domain optical coherence tomography. Results. Gender, age, and axial length did not significantly differ between the groups (all, p > 0.05). The mean values of choroidal thickness in the macular and peripapillary areas (except the superior quadrant) in the patients with PEX syndrome and PEX glaucoma were lower compared with controls (all p < 0.05). The mean values of the macular and peripapillary choroidal thickness in the PEX glaucoma group were lower compared with PEX syndrome group; however this difference was not significant. Conclusions. The findings of this study revealed that macular and peripapillary choroidal thicknesses were decreased in PEX syndrome and PEX glaucoma cases. The role of choroid in the development of glaucomatous damage in patients with PEX syndrome remains unclear. PMID:27403338

  5. Defining the proteome of human iris, ciliary body, retinal pigment epithelium, and choroid.

    PubMed

    Zhang, Pingbo; Kirby, David; Dufresne, Craig; Chen, Yan; Turner, Randi; Ferri, Sara; Edward, Deepak P; Van Eyk, Jennifer E; Semba, Richard D

    2016-04-01

    The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2959, 2867, and 2755 nonredundant proteins with peptide and protein false-positive rates of <0.1% and <1%, respectively. Forty-three unambiguous protein isoforms were identified in iris, ciliary body, and RPE/choroid. Four "missing proteins" were identified in ciliary body based on ≥2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194. PMID:26834087

  6. Automatic Segmentation of Polypoidal Choroidal Vasculopathy from Indocyanine Green Angiography Using Spatial and Temporal Patterns

    PubMed Central

    Lin, Wei-Yang; Yang, Sheng-Chang; Chen, Shih-Jen; Tsai, Chia-Ling; Du, Shuo-Zhao; Lim, Tock-Han

    2015-01-01

    Purpose To develop a computer-aided diagnostic tool for automated detection and quantification of polypoidal regions in indocyanine green angiography (ICGA) images. Methods The ICGA sequences of 59 polypoidal choroidal vasculopathy (PCV) treatment–naïve patients from five Asian countries (Hong Kong, Singapore, South Korea, Taiwan, and Thailand) were provided by the EVEREST study. The ground truth was provided by the reading center for the presence of polypoidal regions. The proposed detection algorithm used both temporal and spatial features to characterize the severity of polypoidal lesions in ICGA sequences. Leave-one-out cross validation was carried out so that each patient was used once as the validation sample. For each patient, a fixed detection threshold of 0.5 on the severity was applied to obtain sensitivity, specificity, and balanced accuracy with respect to the ground truth. Results Our system achieved an average accuracy of 0.9126 (sensitivity = 0.9125, specificity = 0.9127) for detection of polyps in the 59 ICGA sequences. Among the total of 222 features extracted from ICGA sequence, the spatial variances exhibited best discriminative power in distinguishing between polyp and nonpolyp regions. The results also indicated the importance of combining spatial and temporal features to further improve detection accuracy. Conclusions The developed software provided a means of detecting and quantifying polypoidal regions in ICGA images for the first time. Translational Relevance This preliminary study demonstrated a computer-aided diagnostic tool, which enables objective evaluation of PCV and its progression. Ophthalmologists can easily visualize the polypoidal regions and obtain quantitative information about polyps by using the proposed system. PMID:25806144

  7. Case series of choroid plexus papilloma in children at uncommon locations and review of the literature

    PubMed Central

    Prasad, G. Lakshmi; Mahapatra, Ashok Kumar

    2015-01-01

    Background: Choroid plexus papillomas (CPPs) comprise around 1% of intracranial neoplasms. The most common location is atrium of the lateral ventricle in children and fourth ventricle in adults. Other rare locations include third ventricle, cerebellopontine (CP) angle and cerebral parenchyma, with only a few cases reported. Authors report three cases of CPP at uncommon locations in pediatric patients. The rarity of these locations, diagnostic dilemma and management aspects are discussed along with an extensive review of the literature. Methods: Retrospective institutional data analysis of histopathologically confirmed pediatric CPPs from 2010 to 2014. Results: Authors noted three cases of CPP in children in uncommon locations-one each in the posterior third ventricle, fourth ventricle, and CP angle. All were males in the first decade. Two cases presented with features of obstructive hydrocephalus while the latter presented with compressive effects. Complete excision was achieved in two cases while subtotal removal was performed in one case (fourth ventricular) because of excess blood loss. Mean follow-up duration was 24.6 months (range 20–30 months). One case (of subtotal removal) had fair recovery while other two had excellent outcomes. Conclusions: Posterior third ventricle, fourth ventricle, and CP angle are uncommon locations for these tumors in children. Complete surgical removal is the treatment of choice and approach needs to be tailored according to the site and size of the lesion. Blood loss is a major concern in young children as they are highly vascular tumors. Complete removal leads to excellent long-term survival rates. Adjuvant treatment is not required. PMID:26500797

  8. Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis

    PubMed Central

    Liu, Ke; Chen, Li Jia; Hou, Ping; Chen, Weiqi; Pang, Chi Pui

    2012-01-01

    Purpose To investigate the genetic associations of polypoidal choroidal vasculopathy (PCV), the genetic difference between PCV and age-related macular degeneration (AMD), and the genotype-phenotype correlation of PCV. Methods A systematic review and meta-analysis were performed. Published articles about genetic associations of PCV identified from a literature search were reviewed. The following data from individual studies were extracted and analyzed: 1) comparison of genetic polymorphisms between PCV and controls; 2) comparison of genetic polymorphisms between PCV and AMD; and 3) comparison of phenotypes between different genotype groups. Results A total of 33 articles fulfilled the inclusion criteria. With meta-analyses, variants in four genes were found to be significantly associated with PCV: LOC387715 rs10490924 (n=9, allelic odds ratio [OR]=2.27, p<0.00001), HTRA1 rs11200638 (n=4, OR=2.72, p<0.00001), CFH rs1061170 (n=4, OR=1.72, p<0.00001), CFH rs800292 (n=5, OR=2.10, p<0.00001), and C2 rs547154 (n=3, OR=0.56, p=0.01). LOC387715 rs10490924 was the only variant showing a significant difference between PCV and wet AMD (n=5, OR=0.66, p<0.00001). The risk genotypes of rs10490924 were associated with larger lesion size, greater chance of vitreous hemorrhage, and worse therapeutic response in PCV. Conclusions LOC387715 rs10490924 was associated with PCV and its clinical manifestations, and showed a discrepant distribution between PCV and AMD. Variants in HTRA1, CFH, and C2 were also associated with PCV. PMID:22509112

  9. Roles of NFκB-miR-29s-MMP-2 circuitry in experimental choroidal neovascularization

    PubMed Central

    2014-01-01

    Background Previous reports have indicated that matrix metallopeptidase-2 (MMP-2) regulates angiogenic processes, which are involved in choroidal neovascularization (CNV). However, the regulation of MMP-2 in CNV has not been well-characterized. To gain more information about the regulation of MMP-2 in CNV, we analyzed the circuitry associated with MMP-2 regulation in a CNV model and in cell cultures, focusing on NFκB and the microRNA-29 family (miR-29s). Methods The CNV model was established by subjecting C57BL/6 mice to fundus photocoagulation with a krypton red laser. In choroidal-retinal pigment epithelial (RPE) tissues of the model, immunohistochemistry was used to evaluate the angiogenesis and MMP-2 expression; reverse-transcription quantitative PCR (RT-qPCR) was used to determine the levels of miR-29s; and western blot was used to analyze the protein levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitor, IκBα, and its phosphorylated form, phospho-IκBα. At the cellular level, RT-qPCR was used to examine the levels of miR-29s following NFκB activation by tumor necrosis factor alpha (TNFα); and western blot and luciferase assay were used to determine the regulation of MMP-2 by miR-29s in a human RPE cell line (ARPE-19) and in an umbilical vein endothelial cell line (EA hy926). Results MMP-2 staining was increased in the choroidal neovascular membrane of laser-treated retina. Also, the NFκB pathway was induced in choroid-RPE tissue, as evidenced by a lower protein level of IκBα and a higher level of phospho-IκBα in the tissue homogenates than in those from non-treated eyes. During the period when the NFκB pathway was induced, reduced miR-29s were detected in the choroidal-RPE tissue of the laser-treated eyes. In cultured ARPE-19 cells, TNFα decreased miR-29a, b, and c, and the effects were rescued by NFκB decoy. In ARPE-19 and EA hy926, miR-29s mimics reduced the contents of secreted MMP-2 in the culture media

  10. Nerve lesioning with direct current

    NASA Astrophysics Data System (ADS)

    Ravid, E. Natalie; Shi Gan, Liu; Todd, Kathryn; Prochazka, Arthur

    2011-02-01

    Spastic hypertonus (muscle over-activity due to exaggerated stretch reflexes) often develops in people with stroke, cerebral palsy, multiple sclerosis and spinal cord injury. Lesioning of nerves, e.g. with phenol or botulinum toxin is widely performed to reduce spastic hypertonus. We have explored the use of direct electrical current (DC) to lesion peripheral nerves. In a series of animal experiments, DC reduced muscle force by controlled amounts and the reduction could last several months. We conclude that in some cases controlled DC lesioning may provide an effective alternative to the less controllable molecular treatments available today.

  11. The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study

    PubMed Central

    Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B.L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

    2009-01-01

    Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we use an event-related design, which allowed us to isolate trial related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single-subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. PMID:19819000

  12. Correlation of Aging and Segmental Choroidal Thickness Measurement using Swept Source Optical Coherence Tomography in Healthy Eyes

    PubMed Central

    Wakatsuki, Yu; Shinojima, Ari; Kawamura, Akiyuki; Yuzawa, Mitsuko

    2015-01-01

    Purpose To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattler's (CS) layer and/or the large vessel layer in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm. Methods We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan. Results Total choroidal thicknesses at each of the five sites were related to subject age (P<0.0001). The choroid was thinnest at the nasal site, followed by the temporal, inferior, superior and finally the subfoveal site itself. The total choroidal thickness at the nasal site was significantly less than those at the other four sites (p<0.05). The CS layer showed thinning which correlated with age (P<0.0001). The thickness of the choroidal large vessel layer also decreased with age (p = 0.02). Subfoveal choroidal thickness was calculated as follows: 443.89–2.98×age (μm) (P<0.0001). Conclusion Subfoveal choroidal thickness decreases by 2.98 μm each year. Total choroidal thickness diminishes with age. The CS and large vessel layers of the choroid at the subfovea showed significant decreases, though only the former correlated strongly with age. PMID:26632821

  13. Gyrate atrophy of the choroid and retina with hyperornithinemia: characterization of mutant liver L-ornithine:2-oxoacid aminotransferase kinetics.

    PubMed

    Sipilä, I; Simell, O; O'Donnell, J J

    1981-06-01

    Deficient activity of L-ornithine:2-oxoacid aminotransferase is associated with gyrate atrophy of the choroid and retina with hyperornithinemia, an autosomal recessive disease leading to blindness. Liver tissue from two patients contained trace activity of the enzyme. The Michaelis (Km) value of the mutant enzyme for ornithine was 200 mM, 50-fold higher than normal, but increasing the concentrations of alpha-oxoglutarate and pyridoxal 5'-phosphate to 10 times those giving maximal activity of the normal enzyme had no effect on the mutant enzyme. Substrate inhibition of the mutant could not be demonstrated at 1,000 mM ornithine concentration, whereas ornithine concentrations above 70 mM inhibited the normal enzyme. The data suggest that the abnormal L-ornithine:2-oxoacid aminotransferase in the two patients studied has an altered binding site for ornithine. PMID:7240420

  14. Age-Dependent Morphologic Alterations in the Outer Retinal and Choroidal Thicknesses Using Swept Source Optical Coherence Tomography

    PubMed Central

    2016-01-01

    Purpose To evaluate the age-dependent morphologic alterations in the outer retina and choroid at the macula using swept-source optical coherence tomography (OCT). Methods Thirty eyes (30 normal subjects; average age, 49 years) were examined; five (age range, third-eighth decades of life) had refractive errors of ±2 diopters or less and no fundus abnormalities. An Early Treatment Diabetic Retinopathy Study (ETDRS) map of the outer retinal and choroidal thickness was constructed using swept-source OCT. The outer retinal and choroidal segmentation lines were drawn automatically, partially manually, within 6 millimeters of the macula. Results The mean outer retinal and choroidal thicknesses in the 6-millimeter-diameter circle were 145±13 and 236±68 microns, respectively. The choroidal thickness and age were negatively (r = -0.66, P<0.01) correlated; the outer retinal thickness and age were not correlated (r = -0.16, P = 0.39). The outer retinal and choroidal thicknesses in the ETDRS map were not correlated (r = -0.13, P = 0.49) within 1 millimeter but correlated (r = 0.32, P<0.01) within 6 millimeters. Conclusions The choroid thins with aging. The outer retina remains stable. Outer retina and choroid are correlated in the entire macula except for the center. ETDRS map can be useful for evaluation of the morphologic relationship between the outer retina and choroid. PMID:27467879

  15. Structural Changes of Inner and Outer Choroid in Central Serous Chorioretinopathy Determined by Optical Coherence Tomography

    PubMed Central

    Sonoda, Shozo; Sakamoto, Taiji; Kuroiwa, Nobuhiro; Arimura, Noboru; Kawano, Hiroki; Yoshihara, Naoya; Yamashita, Takehiro; Uchino, Eisuke; Kinoshita, Takamasa; Mitamura, Yoshinori

    2016-01-01

    Purpose To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT). Methods A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas. Results In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P<0.01 vs control for both, Wilcoxon signed-rank test). In the outer choroid, the hyporeflective area was significantly larger in the CSC eyes (446,549±121,214 μm2) than the control eyes (235,680±97,352 μm2, P<0.01). The average ratio of the hyporeflective area to the total choroidal area was smaller in the CSC eyes (67.0%) than the fellow eyes (76.5%) and the control eyes (76.7%) in the inner choroid (P<0.01, both). However, the ratio was larger in the CSC eyes (75.2%) and fellow eyes (71.7%) than in the control eyes (64.7%) in the outer choroid (P<0.01, both). Conclusions The larger hyperreflective area in the inner choroid is related to the inflammation and edema of the stroma of the choroid in the acute stage of CSC. The larger hyporeflective areas in the outer choroid is due to a dilatation of the vascular lumens of the larger blood vessels. These are the essential characteristics of eyes with CSC regardless of the onset. PMID:27305042

  16. Gastroprotective Activity of Polygonum chinense Aqueous Leaf Extract on Ethanol-Induced Hemorrhagic Mucosal Lesions in Rats

    PubMed Central

    Ismail, Iza Farhana; Abdul Majid, Nazia; Kadir, Farkaad A.; Al-Bayaty, Fouad; Awang, Khalijah

    2012-01-01

    Polygonum chinense is a Malaysian ethnic plant with various healing effects. This study was to determine preventive effect of aqueous leaf extract of P. chinense against ethanol-induced gastric mucosal injury in rats. Sprague Dawley rats were divided into seven groups. The normal and ulcer control groups were orally administered with distilled water. The reference group was orally administered with 20 mg/kg omeprazole. The experimental groups received the extracts 62.5, 125, 250, and 500 mg/kg, accordingly. After sixty minutes, distilled water and absolute ethanol were given (5 mL/kg) to the normal control and the others, respectively. In addition to histology, immunohistochemical and periodic acid schiff (PAS) stains, levels of lipid peroxidation, malondialdehyde (MDA), antioxidant enzymes, and superoxide dismutase (SOD) were measured. The ulcer group exhibited severe mucosal damages. The experimental groups significantly reduced gastric lesions and MDA levels and increased SOD level. Immunohistochemistry of the experimental groups showed upregulation and downregulation of Hsp70 and Bax proteins, respectively. PAS staining in these groups exhibited intense staining as compared to the ulcer group. Acute toxicity study revealed the nontoxic nature of the extract. Our data provide first evidence that P. chinense extract could significantly prevent gastric ulcer. PMID:23365597

  17. [Ocular fundus lesions in systemic lupus erythematosus model mice].

    PubMed

    Nakamura, A; Yokoyama, T; Kodera, S; Zhang, D; Hirose, S

    1998-01-01

    To evaluate spontaneous development of the ocular fundus abnormalities associated with collagen disease, we investigated the ocular fundus lesions in systemic lupus erythematosus (SLE) models. (NZW x BXSB) F1 mice were employed as SLE models with antiphospholipid syndrome. The abnormal findings in the ocular fundus were recorded with a fundus camera for small animals (KOWA Co., Ltd.), and the chorioretinal lesions were studied histopathologically. As in the systemic symptoms of SLE, the incidence of ocular fundus abnormalities in these (NZW x BXSB) F1 mice was significantly higher in males than in females, suggesting the influence of the Yaa (Y chromosome-linked autoimmune acceleration) gene. Lesions in the fundus appeared in the form of white spots, which increased in number along with the course of the disease. The lesion developed into retinal detachment in some animals. Dilatation of veins and narrowing of arteries were marked. These lesions were very similar to multifocal posterior pigment epitheliopathy (MPPE) in humans in that white spots appear first and then develop into exudative retinal detachment caused by retinal pigment epithelial disorder. Histopathological findings included 1. structural destruction of the photoreceptor cell layer, 2. degeneration and loss of the retinal pigment epithelium, and 3. narrowing and occlusion of the choriocapillaris associated with thrombus formation, cellular infiltration into the surrounding tissues, and wall thickening of the choroidal arterioles. The study of these SLE mouse may contribute to the elucidation of abnormalities in the fundus associated with collagen diseases, including the relationship between thrombus formation and antiphospholipid syndrome. PMID:9489364

  18. Effect of charred Radix et Rhizoma Rhei in a laser-induced choroidal neovascularization murine model.

    PubMed

    Han, Dongmei; Yao, Yuan; Sun, Yong; Gong, Yuanyuan; Wu, Xingwei

    2015-04-01

    A pharmaceutical composition (patent no. WO2012079419) exhibited favorable outcomes in a clinical trial of wet age‑related macular degeneration. The aims of the present study were to explore the effects of one composition component, charred Radix et Rhizoma Rhei (CRRR), in a laser‑induced choroidal neovascularization (CNV) murine model. A total of 30 eight‑week‑old C57BL/6 mice were subjected to diode laser treatment, and CNV was induced by rupturing the Bruch's membrane. The mice were then randomly divided into two groups: the CRRR‑treated group that was administered CRRR water extract (concentration, 0.6 g/100 ml; dose, 1 ml/0.1 kg twice a day for 21 days); and the control group that was treated with saline (dose, 1 ml/0.1 kg twice a day for 21 days). The retinal tissue was subjected to quantitative polymerase chain reaction (qPCR) and western blot analysis to determine the expression levels of interleukin‑10 (IL‑10) and vascular epithelial growth factor (VEGF) at day seven following laser treatment. At weeks 2 and 3 after laser treatment, fundus fluorescein angiography was performed and graded to assess the severity of lesion leakage. Retinal flat mounts were prepared for three‑dimensional confocal microscopy at day 22 after laser treatment. At days 14 and 21 after laser treatment, no statistically significant differences were observed between the clinically relevant lesions of the CRRR‑treated and control mice. CNV volumes were not found to be significantly different between the CRRR‑treated and control mice. The expression levels of IL‑10 were significantly increased in the CRRR‑treated mice (P<0.05). However, no statistically significant differences were observed between the VEGF expression levels of the CRRR‑treated and control mice. In conclusion, CRRR did not appear to significantly inhibit CNV in this murine model. The function of CRRR in the pharmaceutical composition may be due to the effects of IL‑10 and a synergistic effect

  19. Choroid plexus of the fourth ventricle: Review and anatomic study highlighting anatomical variations.

    PubMed

    Tubbs, R Shane; Shoja, Mohammadali M; Aggarwal, Anjali; Gupta, Tulika; Loukas, Marios; Sahni, Daisy; Ansari, Shaheryar F; Cohen-Gadol, Aaron A

    2016-04-01

    Relatively few studies have been performed that analyze the morphology of the choroid plexus of the fourth ventricle. Due to the importance of this tissue as a landmark on imaging and during surgical intervention of the fourth ventricle, the authors performed a cadaveric study to better characterize this important structure. The choroid plexus of the fourth ventricle of 60 formalin fixed adult human brains was examined and measured. The horizontal distance from the midline to the lateral most point of the protruding tip of the horizontal limbs was measured. In the majority of the 60 brain specimens, right and left horizontal limbs of the choroid plexus were seen extending from the midline and protruding out of their respective lateral apertures of the fourth ventricle and into the subarachnoid space. However, on 3.3% of sides, there was absence of an extension into the foramen of Luschka and in one specimen, this lack of extension into the foramen of Luschka was bilateral. On two sides, there was discontinuity between the midline choroid plexus and the tuft of choroid just outside the foramen of Luschka. For specimens in which the choroid plexus did protrude through the foramen of Luschka (96.7%), these tufts were located anterior to the flocculus and inferolateral to the facial/vestibulocochlear nerve complex and posterosuperior to the glossopharyngeal/vagal/accessory complex. A thorough understanding of the normal and variant anatomy of the fourth ventricular choroid plexus is necessary for those who operate in, or interpret imaging of, this region. PMID:26675624

  20. Blood Flow Velocity in the Choroid in Punctate Inner Choroidopathy and Vogt-Koyanagi Disease:. and Multifractal Analysis of Choroidal Blood Flow in Age-Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Yoshida, K.; Saito, W.; Fujii, H.; Yakubo, K.

    2007-07-01

    Recently, the important role of the choroidal circulation has been recognized in various fundus diseases, such as punctate inner choroidopathy (PIC), Vogt-Koyanagi-Harada (VKH) disease, and age-related macular degeneration (AMD). An apparatus based on the laser speckle phenomenon, which we call laser speckle flowgraphy (LSFG) has been used to measure the blood flow velocity in the retina and choroid with the diode laser. PIC presents in myopic women who complain of decreased visual acuity. VKH disease is a bilateral, granulomatous chorioretinitis. The composite map of the LSFG represent that blood flow velocity in the choroid was decreased in PIC and VKH. After the treatment, blood flow velocity in this area was increased in both disease and visual acuity recovered. LSFG appears to be a safe and sensitive means to evaluate these disease progression and response to therapy. A multifractal analysis has been performed for blood flow data in the composite map of the LSFG. In consequence, multifractality becomes clearly worse for the AMD patient compared to normal choroidal blood flows. The multifractal analysis of LSFG data represents an additional useful method to detect the early stage of AMD.

  1. Novel repair activities of AlkA (3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid

    PubMed Central

    Terato, Hiroaki; Masaoka, Aya; Asagoshi, Kenjiro; Honsho, Akiko; Ohyama, Yoshihiko; Suzuki, Toshinori; Yamada, Masaki; Makino, Keisuke; Yamamoto, Kazuo; Ide, Hiroshi

    2002-01-01

    Nitrosation of guanine in DNA by nitrogen oxides such as nitric oxide (NO) and nitrous acid leads to formation of xanthine (Xan) and oxanine (Oxa), potentially cytotoxic and mutagenic lesions. In the present study, we have examined the repair capacity of DNA N-glycosylases from Escherichia coli for Xan and Oxa. The nicking assay with the defined substrates containing Xan and Oxa revealed that AlkA [in combination with endonuclease (Endo) IV] and Endo VIII recognized Xan in the tested enzymes. The activity (Vmax/Km) of AlkA for Xan was 5-fold lower than that for 7-methylguanine, and that of Endo VIII was 50-fold lower than that for thymine glycol. The activity of AlkA and Endo VIII for Xan was further substantiated by the release of [3H]Xan from the substrate. The treatment of E.coli with N-methyl-N′-nitro-N-nitrosoguanidine increased the Xan-excising activity in the cell extract from alkA+ but not alkA– strains. The alkA and nei (the Endo VIII gene) double mutant, but not the single mutants, exhibited increased sensitivity to nitrous acid relative to the wild type strain. AlkA and Endo VIII also exhibited excision activity for Oxa, but the activity was much lower than that for Xan. PMID:12434002

  2. Choroidal thickness profiles in myopic eyes of young adults in the Correction of Myopia Evaluation Trial cohort

    PubMed Central

    Harb, Elise; Hyman, Leslie; Gwiazda, Jane; Marsh-Tootle, Wendy; Zhang, Qinghua; Hou, Wei; Norton, Thomas T; Weise, Katherine; Dirkes, Keri; Zangwill, Linda M

    2015-01-01

    Purpose To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. Design Cross-sectional, multi-center, study Methods In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid (RTVue) in both eyes at their last visit (14 years after baseline). Using digital calipers, two independent readers measured choroidal thickness in the right eye (left eye if poor quality; n=37) at seven locations: fovea and 750, 1500, 2250μm nasal (N) and temporal (T) to the fovea. Results Choroidal thickness measurements were available from 294/346 (85%) of imaged participants (mean age: 24.3±1.4 years; 44.9% male) with mean myopia of -5.3±2.0D and mean AL of 25.5±1.0mm. Overall, choroidal thickness varied by location (p<0.0001) and was thickest at the fovea (273.8±70.9 μm) and thinnest nasally (N2250,191.5±69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (p≤0.001) and presence of peri-papillary crescent at all locations except T1500 and T2250 (p≤0.0001). Choroidal thickness varied by ethnicity at N2250 (p<0.0001), with Asians having the thinnest and African Americans the thickest choroids. Conclusion Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically. PMID:25896460

  3. Myopic choroidal neovascularisation: current concepts and update on clinical management

    PubMed Central

    Wong, Tien Y; Ohno-Matsui, Kyoko; Leveziel, Nicolas; Holz, Frank G; Lai, Timothy Y; Yu, Hyeong Gon; Lanzetta, Paolo; Chen, Youxin; Tufail, Adnan

    2015-01-01

    Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm. PMID:24990871

  4. Evaluation of Subfoveal Choroidal Thickness in Internal Carotid Artery Stenosis

    PubMed Central

    Akçay, Betül İlkay Sezgin; Kardeş, Esra; Maçin, Sultan; Ünlü, Cihan; Özgürhan, Engin Bilge; Maçin, Aydın; Bozkurt, Tahir Kansu; Ergin, Ahmet; Surmeli, Reyhan

    2016-01-01

    Purpose. To evaluate the relationship between internal carotid artery (ICA) stenosis and subfoveal choroidal thickness (SFCT) in the elderly population. Methods. A total of 42 eyes of 21 patients with more than 70% ICA stenosis (Group 1) on one side and less than 70% stenosis (Group 2) on the other side were recruited for this study. ICA stenosis was diagnosed using both the B-mode and Doppler ultrasound. The two groups were compared in terms of the percentage of stenosis, SFCT measurements, intraocular pressure, ocular perfusion pressure, refractive error, and peak systolic velocity. Eyes were examined with the RTVue-100 OCT device by the EDI-OCT technique. Results. The mean age of the patients was 71.9 ± 10.8 years. The mean percentage of ICA stenosis was 74 ± 4.9% in Group 1 and 47.5 ± 7.7% in Group 2. The mean SFCT was 231.9 ± 44.6 μm in Group 1 and 216.2 ± 46.8 μm in Group 2, which was significantly lower (P = 0.028). A statistically significant positive correlation was found between the percentage of internal carotid artery stenosis and SFCT (r = 0896, P = 0.001). Conclusions. Compensatory SFCT increase can be seen in ipsilateral internal carotid artery stenosis greater than 70%. PMID:26989500

  5. Myopic choroidal neovascularisation: current concepts and update on clinical management.

    PubMed

    Wong, Tien Y; Ohno-Matsui, Kyoko; Leveziel, Nicolas; Holz, Frank G; Lai, Timothy Y; Yu, Hyeong Gon; Lanzetta, Paolo; Chen, Youxin; Tufail, Adnan

    2015-03-01

    Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm. PMID:24990871

  6. Change in subfoveal choroidal thickness after argon laser panretinal photocoagulation

    PubMed Central

    Cho, Ga Eun; Cho, Hee Yun; Kim, Yun Taek

    2013-01-01

    AIM To evaluate changes in subfoveal choroidal thickness (SFCT) and macular thickness as measured by enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) after argon laser panretinal photocoagulation (PRP) in patients with severe diabetic retinopathy. METHODS This prospective, comparative case series included 21 patients (28 eyes) with severe diabetic retinopathy. All patients underwent three sessions of PRP. The SFCT and macular thickness were measured using EDI-OCT at baseline and one week after completion of 3 sessions of PRP. RESULTS SFCT before PRP was (318.1±96.5)µm and increased to (349.9±108.3)µm (P=0.001) after PRP. Macular thickness significantly increased at one week after PRP (from 273.1±23.9µm at baseline vs 295.8±25.3µm at one week; P<0.001). No significant relationship between the changes in macular thickness and SFCT was observed (r=-0.13, P=0.52). CONCLUSION PRP induced increases in both SFCT and macular thickness. Changes in SFCT did not correlate with changes in macular thickness. PMID:23991387

  7. Inhibition of Elastin Peptide-Mediated Angiogenic Signaling Mechanism(s) in Choroidal Endothelial Cells by the α6(IV)NC1 Collagen Fragment

    PubMed Central

    Gunda, Venugopal; Verma, Raj Kumar; Sudhakar, Yakkanti Akul

    2013-01-01

    Purpose. The inhibitory effects and mechanism(s) of type IV collagen α-6 chain–derived noncollagenous domain (α6[IV]NC1 or hexastatin) on elastin-derived peptide (EDP)–activated choroidal endothelial cell migration, kinase signaling, and membrane type 1 metalloproteinase (MT1-MMP) activation are explored. Methods. Mouse choroidal endothelial cells (MCECs) were incubated in media with soluble EDPs (kappa elastin, mouse elastin, and Val-Gly-Val-Ala-Pro-Gly [VGVAPG] hexapeptide) for different time intervals with or without α6(IV)NC1. The MCECs proliferation, migration, tube formation, MT1-MMP expression, and angiogenic signaling were analyzed in cells subjected to EDP and α6(IV)NC1 treatments. The MCECs also were subjected to EDPs, and specific inhibitors for evaluation of focal adhesion kinase (FAK) and protein kinase B (Akt) phosphorylation. Results. Kappa elastin, mouse elastin, and VGVAPG enhanced the migration, without affecting the proliferation of MCECs. The α6(IV)NC1 inhibited survival and EDP-activated migration of MCECs. The EDP-activated MCEC tube formation on matrigel also was inhibited by α6(IV)NC1. Further, EDP-activated MT1-MMP expression and FAK/phosphoinositide-3-kinase (PI-3K)/mammalian target of rapamycin (mToR)/Akt phosphorylation in MCECs, were reduced by α6(IV)NC1. The EDP-induced FAK and Akt phosphorylation was blocked by FAK- and Akt-specific inhibitors. Conclusions. The EDPs and α6(IV)NC1 are identified to exhibit opposing effects on MCEC angiogenic behavior and signaling. The α6(IV)NC1 inhibited cell survival, EDP-mediated migration, MT1-MMP expression and, FAK/PI-3K/mToR/Akt phosphorylation in MCECs. This work demonstrates α6(IV)NC1 as a prospective endogenous molecule for the treatment of diseases involving choroidal neovascularization in the eye. PMID:24194191

  8. Clinical and radiographical evaluation of the healing of large periapical lesions using triple antibiotic paste, photo activated disinfection and calcium hydroxide when used as root canal disinfectant

    PubMed Central

    Varughese, Jolly M.; Thomas, Kunjamma; Abraham, Aby; James, Elizabeth P.; Maroli, Ramesh K.

    2014-01-01

    Objectives: To evaluate clinically and radio graphically, the healing following nonsurgical treatment of periapical lesions when Photo Activated Disinfection(PAD), triple antibiotic paste and calcium hydroxide was used as root canal disinfectant. Material and Methods: Sixty patients (20 for PAD, 20 for triple antibiotic paste, 20 for calcium hydroxide) with periapical lesions in the maxillary and mandibular anterior region were selected from the outpatient section of the Department of Conservative Dentistry & Endodontics, Govt. Dental College, Kozhikode to participate in this study. The patients were selected with a preoperative score of 4 or 5. There were no significant differences for the PAI Scores between the three groups at the start of the experiment .Intracanal disinfection was done in the three groups followed by obturation. The patients recalled at 3,6,12,18 months interval. Results: At 18 months follow up 15 % of cases failed in calcium hydroxide group,5% in triple antibiotic paste and no failure cases were seen in PAD group. Success criteria were divided into strict and loose, while the former had statistically significant p value the latter did not. Kruskal-Wallis Test showed an increased mean value for PDT and a significant change in p value. Bonferroni post hoc test was done to compare if there is any significant change between groups. Only significant change was found between calcium hydroxide and photoactivated disinfection . Conclusion: PAD was more effective intracanal disinfectant at 6,12 and 18 months. Key words:Calcium, hydroxide, photo activated disinfection, triple antibiotic paste, root canal disinfection PMID:25136422

  9. Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

    PubMed

    Abedalthagafi, Malak S; Wu, Michael P; Merrill, Parker H; Du, Ziming; Woo, Terri; Sheu, Shu-Hsien; Hurwitz, Shelley; Ligon, Keith L; Santagata, Sandro

    2016-03-01

    Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690880

  10. Choroidal atrophy in a patient with paraneoplastic retinopathy and anti-TRPM1 antibody.

    PubMed

    Ueno, Shinji; Ito, Yasuki; Maruko, Ruka; Kondo, Mineo; Terasaki, Hiroko

    2014-01-01

    The purpose of this paper is to report choroidal atrophy in a patient with cancer-associated retinopathy who had autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1). A 69-year-old man visited our clinic in July 2010 with complaints of blurred vision and night blindness in both eyes. The full-field electroretinograms were negative type, indicating ON bipolar cell dysfunction. General physical examination revealed small cell carcinoma of the lung, and Western blot of the patient's serum showed autoantibodies against TRPM1. We diagnosed this patient with cancer-associated retinopathy and retinal ON bipolar dysfunction due to anti-TRPM1 autoantibody. We followed him for more than 2 years from the initial visit and his symptoms have not changed. However, consistent with the choroidal hypopigmentation of the fundus, spectral domain optical coherence tomography showed a decrease in choroidal thickness of about one third over a 2-year follow-up period. We suggest that this case of gradually progressive choroidal atrophy was caused by the autoantibody against TRPM1 directly, because TRPM1 is expressed not only on ON bipolar cells but also on melanocytes. These findings indicate that we should be aware of choroidal thickness in patients with paraneoplastic retinopathy who have retinal ON bipolar dysfunction with the anti-TRPM1 antibody. PMID:24523577

  11. Decreased prevalence of asymptomatic choroidal metastasis in disseminated breast and lung cancer: argument against screening

    PubMed Central

    Barak, A; Neudorfer, M; Heilweil, G; Merimsky, O; Lowenstein, A; Inbar, M; Yaal‐Hahoshen, N

    2007-01-01

    Aim To determine the frequency of visually asymptomatic choroidal metastases in patients with disseminated breast and lung carcinomas in order to establish optimal patient management policies. Methods All patients with confirmed metastatic disease treated in our institution between January 2002 and December 2003 were invited to undergo a funduscopic examination and a B‐scan ultrasound evaluation. Results Of the 169 study participants, 77 had breast cancer (64 with metastases in one organ and 13 with multiple‐organ involvement) and 92 had lung cancer (85 with metastases in one organ and 7 with multiple‐organ involvement). No patient with metastatic breast cancer and two patients with metastatic lung disease (each with multiple‐organ involvement) were found to have choroidal metastases. The choroidal metastases were detected by both the funduscopic and ultrasound examinations. Conclusions The 2.17% incidence of choroidal metastasis in disseminated lung cancer and the 0% incidence in disseminated breast cancer speaks against the practicality of screening for early detection of choroidal metastasis among these patients, even though it would lead to early implementation of appropriate, often vision saving, therapeutic management. Its low incidence probably testifies to progress achieved by enhanced systemic oncological treatment policies that have been introduced into routine patient management over the past few years. PMID:16943227

  12. Retinal Vessel Caliber, Choroidal Thickness and Ocular Pulse Amplitude Measurements in Essential Thrombocythemia

    PubMed Central

    Pekel, Gökhan; Doğu, Mehmet Hilmi; Sarı, Hakan Ismail; Acer, Semra; Kasikci, Alper; Yagci, Ramazan; Çetin, Ebru Nevin

    2016-01-01

    Purpose: The choroid and retina receive most of the blood that enter to the eye, and this uptake may be affected by essential thrombocythemia (ET) in which thrombosis and hemorrhage is common. This study compares choroidal thickness, retinal vascular caliber, and ocular pulse amplitude (OPA) measurements between patients with ET and healthy adults. Materials and Methods: Thirty-seven patients with ET and 37 age-sex-matched healthy adults were recruited in this cross-sectional and comparative study. Spectral-domain optical coherence tomography was used to measure the subfoveal choroidal thickness (SFCT) and retinal vascular caliber measurements. The Pascal dynamic contour tonometer was used for OPA and intraocular pressure (IOP) measurements. The independent samples t-test was used for comparison of measurements between the groups. Pearson's correlation coefficient analysis was used to detect correlations between the variables. A P < 0.05 was statistically significant. Results: SFCT, OPA, and IOP measurements were not statistically significant differences between the study group and the control group (P > 0.05, all comparisons). Blood platelet counts were not associated with choroidal thickness, OPA, and IOP (P > 0.05). Retinal arteriolar and venular calibers were statistically, significantly thicker in healthy controls when compared to the study group (P < 0.05). Conclusions: Our results indicate that choroidal thickness and pulsatile blood flow are not significantly affected in ET and under high blood platelet counts. Retinal arteriolar and venular calibers are thinner in ET when compared to age-sex matched healthy controls. PMID:26957845

  13. Choroid plexus implants rescue Alzheimer's disease-like pathologies by modulating amyloid-β degradation.

    PubMed

    Bolos, Marta; Antequera, Desireé; Aldudo, Jesús; Kristen, Henrike; Bullido, María Jesús; Carro, Eva

    2014-08-01

    The choroid plexuses (CP) release numerous biologically active enzymes and neurotrophic factors, and contain a subpopulation of neural progenitor cells providing the capacity to proliferate and differentiate into other types of cells. These characteristics make CP epithelial cells (CPECs) excellent candidates for cell therapy aiming at restoring brain tissue in neurodegenerative illnesses, including Alzheimer's disease (AD). In the present study, using in vitro approaches, we demonstrated that CP were able to diminish amyloid-β (Aβ) levels in cell cultures, reducing Aβ-induced neurotoxicity. For in vivo studies, CPECs were transplanted into the brain of the APP/PS1 murine model of AD that exhibits advanced Aβ accumulation and memory impairment. Brain examination after cell implantation revealed a significant reduction in brain Aβ deposits, hyperphosphorylation of tau, and astrocytic reactivity. Remarkably, the transplantation of CPECs was accompanied by a total behavioral recovery in APP/PS1 mice, improving spatial and non-spatial memory. These findings reinforce the neuroprotective potential of CPECs and the use of cell therapies as useful tools in AD. PMID:24343520

  14. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    PubMed Central

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

  15. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA

    PubMed Central

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 108 dm3 mol−1 s−1 and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10–1000 μmol dm−3) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid. PMID:25212600

  16. [Active forms of oxygen: cytotoxic effects and methodological approaches to laboratory control of liver lesions (literature review)].

    PubMed

    Matiushin, B N; Loginov, A S

    1996-01-01

    The injurious effects of active oxygen forms (AOF) on the cell caused by destruction of its membranous structures and impairment of their functional characteristics are discussed. Disorders of the processes of formation and inactivation of AOF in hepatocytes may be the metabolic mechanisms mediating the status and development of the pathological process in the liver. The problem of prospective approaches to assessing chronic diseases of the liver at the level of "free-radical pathology" is discussed. PMID:8963562

  17. Sex differences in the activity of signalling pathways and expression of G-protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model of schizophrenia

    PubMed Central

    Bychkov, Evgeny; Ahmed, M. Rafiuddin; Gurevich, Eugenia V.

    2010-01-01

    Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered responsiveness to stress and various drugs reminiscent of that in schizophrenia. Post-pubertal onset of abnormalities suggests the possibility of sex differences in NVHL effects that may model sex differences in schizophrenia. Here we demonstrate that novelty- and MK-801-induced hyperactivity is evident in both male and female NVHL rats, whereas only NVHL males were hyperactive in response to apomorphine. Next, we examined the sex- and NVHL-dependent differences in the activity of the ERK and Akt pathways. The basal activity of both pathways was higher in females than in males. NVHL reduces the level of phosphorylation of ERK1/2, Akt, and GSK-3 in both sexes, although males show more consistent downregulation. Females had higher levels of G-protein-coupled kinases [G-protein-coupled receptor kinase (GRK)] 3 and 5, whereas the concentrations of other GRKs and arrestins were the same. In the nucleus accumbens, the concentration of GRK5 in females was elevated by NVHL to the male level. The data demonstrate profound sex differences in the expression and activity of signalling molecules that may underlie differential susceptibility to schizophrenia. PMID:20158934

  18. Characterization of Choroidal Layers in Normal Aging Eyes Using Enface Swept-Source Optical Coherence Tomography

    PubMed Central

    Mullins, Robert F.; Baumal, Caroline R.; Mohler, Kathrin J.; Kraus, Martin F.; Liu, Jonathan; Badaro, Emmerson; Alasil, Tarek; Hornegger, Joachim; Fujimoto, James G.; Duker, Jay S.; Waheed, Nadia K.

    2015-01-01

    Purpose To characterize qualitative and quantitative features of the choroid in normal eyes using enface swept-source optical coherence tomography (SS-OCT). Methods Fifty-two eyes of 26 consecutive normal subjects were prospectively recruited to obtain multiple three-dimensional 12x12mm volumetric scans using a long-wavelength high-speed SS-OCT prototype. A motion-correction algorithm merged multiple SS-OCT volumes to improve signal. Retinal pigment epithelium (RPE) was segmented as the reference and enface images were extracted at varying depths every 4.13μm intervals. Systematic analysis of the choroid at different depths was performed to qualitatively assess the morphology of the choroid and quantify the absolute thicknesses as well as the relative thicknesses of the choroidal vascular layers including the choroidal microvasculature (choriocapillaris, terminal arterioles and venules; CC) and choroidal vessels (CV) with respect to the subfoveal total choroidal thickness (TC). Subjects were divided into two age groups: younger (<40 years) and older (≥40 years). Results Mean age of subjects was 41.92 (24-66) years. Enface images at the level of the RPE, CC, CV, and choroidal-scleral interface were used to assess specific qualitative features. In the younger age group, the mean absolute thicknesses were: TC 379.4μm (SD±75.7μm), CC 81.3μm (SD±21.2μm) and CV 298.1μm (SD±63.7μm). In the older group, the mean absolute thicknesses were: TC 305.0μm (SD±50.9μm), CC 56.4μm (SD±12.1μm) and CV 248.6μm (SD±49.7μm). In the younger group, the relative thicknesses of the individual choroidal layers were: CC 21.5% (SD±4.0%) and CV 78.4% (SD±4.0%). In the older group, the relative thicknesses were: CC 18.9% (SD±4.5%) and CV 81.1% (SD±4.5%). The absolute thicknesses were smaller in the older age group for all choroidal layers (TC p=0.006, CC p=0.0003, CV p=0.03) while the relative thickness was smaller only for the CC (p=0.04). Conclusions Enface SS-OCT at

  19. Effect of timolol on sub-foveal choroidal blood flow using laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Palanisamy, Nithiyanantham; Rovati, Luigi; Cellini, Mauro; Gizzi, Corrado; Strobbe, Ernesto; Campos, Emilio; Riva, Charles E.

    2011-03-01

    Laser Doppler flowmetry (LDF) is a technique used to measure relative average velocity, number and flux (number times velocity) of red blood cells in vessels or capillaries. In this study, the effect of topical timolol on the choroidal circulation was investigated in 12 healthy subjects. Maximum velocity of red blood cells and volumetric blood flow rate in sub-foveal choroids are determined in each eye just before instillation of drops and then every 30 min upto 2 hours. Average intraocular pressure (IOP) decreased significantly in the timolol-treated eyes compared to that of placebo-treated eyes. Nevertheless no significant differences in choroidal blood hemodynamic between timolol and placebo-treated eyes were observed.

  20. Film dosimetry analyses on the effect of gold shielding for Iodine-125 eye plaque therapy for choroidal melanoma

    SciTech Connect

    Wu, A. ); Krasin, F. )

    1990-09-01

    One of the methods currently being used to treat choroidal melanoma employs an episcleral plaque containing I-125 radioactive seeds. However, comprehensive dosimetry studies on the plaque are scarce and controversial. For this work, we use film to study the dosimetry outside the lip of the gold shield of the eye plaque. This lip around the gold shield was made to protect the critical structures behind and adjacent to the lesion. Since the changes of energy spectrum of I-125 in tissue are negligible, film dosimetry seems to be a logical choice because of high spatial resolution required around the lip of the gold plaque. For this study, we first established an H and D curve with dose expressed in a unit of specific dose rate constant. This avoids absolute dose measurements. All film density measurements are made with a 1-mm aperture scan, normalized to the density at the prescription point for tumor of 3--5-mm apical height, i.e., 5 mm from the interior surface of sclera, and converted to percentage isodose curves. With a gold shield, it is found that when the plaque is placed against the optical nerve, the optical disk and macula, located at 2 mm outside the lip, on the exterior surface of sclera, may receive 85% of the prescription dose for a 12-mm plaque and 58% for a 16-mm plaque. For tumors of 8-mm apical height, the optical nerve would receive more than the prescription dose.

  1. 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease.

    PubMed

    Zamagni, E; Nanni, C; Gay, F; Pezzi, A; Patriarca, F; Bellò, M; Rambaldi, I; Tacchetti, P; Hillengass, J; Gamberi, B; Pantani, L; Magarotto, V; Versari, A; Offidani, M; Zannetti, B; Carobolante, F; Balma, M; Musto, P; Rensi, M; Mancuso, K; Dimitrakopoulou-Strauss, A; Chauviè, S; Rocchi, S; Fard, N; Marzocchi, G; Storto, G; Ghedini, P; Palumbo, A; Fanti, S; Cavo, M

    2016-02-01

    Identification of patient sub-groups with smoldering multiple myeloma (SMM) at high risk of progression to active disease (MM) is an important goal. 18F-FDG PET/CT (positron emission tomography (PET) integrated with computed tomography (PET/CT) using glucose labelled with the positron-emitting radionuclide (18)F) allows for assessing early skeletal involvement. Identification of osteolytic lesions by this technique has recently been incorporated into the updated International Myeloma Working Group criteria for MM diagnosis. However, no data are available regarding the impact of focal lesions (FLs) without underlying osteolysis on time to progression (TTP) to MM. We hence prospectively studied a cohort of 120 SMM patients with PET/CT. PET/CT was positive in 16% of patients (1 FL: 8, 2 FLs: 3, >3 FLs: 6, diffuse bone marrow involvement: 2). With a median follow-up of 2.2 years, 38% of patients progressed to MM, in a median time of 4 years, including 21% with skeletal involvement. The risk of progression of those with positive PET/CT was 3.00 (95% confidence interval 1.58-5.69, P=0.001), with a median TTP of 1.1 versus 4.5 years for PET/CT-negative patients. The probability of progression within 2 years was 58% for positive versus 33% for negative patients. In conclusion, PET/CT positivity significantly increased the risk of progression of SMM to MM. PET/CT could become a new tool to define high-risk SMM. PMID:26490489

  2. Inhibition of development of laser-induced choroidal neovascularization with suppression of infiltration of macrophages in Smad3-null mice.

    PubMed

    Iwanishi, Hiroki; Fujita, Norihito; Tomoyose, Katsuo; Okada, Yuka; Yamanaka, Osamu; Flanders, Kathleen C; Saika, Shizuya

    2016-06-01

    We evaluated the effects of the loss of Smad3 on the development of experimental argon laser-induced choroidal neovascularization (CNV) in mice. An in vitro angiogenesis model was also used to examine the role of transforming growth factor-β1 (TGFβ1)/Smad3 signaling in vessel-like tube formation by human umbilical vein endothelial cells (HUVECs). CNV was induced in eyes of 8-12-week-old B6.129-background Smad3-deficient (KO) mice (n=47) and wild-type (WT) mice (n=47) by argon laser irradiation. Results showed that the size of the CNV induced was significantly smaller in KO mice as compared with WT mice at day 14 as revealed by high-resolution angiography with fluorescein isothiocyanate-dextran. Immunohistochemistry and real-time reverse transcription-polymerase chain reaction of RNA extracted from laser-irradiated choroidal tissues were conducted on specimens at specific timepoints. Invasion of macrophages (F4/80+), but not neutrophils (myeloperoxidase+), and appearance of myofibroblasts (α-smooth muscle actin+) were suppressed in laser-irradiated KO tissues. mRNA expression of inflammation-related factors, that is, vascular endothelial growth factor (VEGF), macrophage-chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and TGFβ1 in choroidal tissues was suppressed by the loss of Smad3. We then examined the effects of adding a Smad3 inhibitor, SIS3, or an ALK5 inhibitor, SB431542, on tube formation promoted by TGFβ1 or VEGF in HUVECs cocultured with fibroblast feeder. Further addition of SIS3 or SB431542 augmented vessel-like tube formation by HUVECs in the presence of TGFβ1 or VEGF. In conclusion, lack of Smad3 attenuated the growth of laser-induced CNV with suppression of inflammation by macrophages in mice. Because blocking TGFβ1/Smad3 signal stimulated the activity of angiogenesis of HUVECs in vitro, the reduction of CNV in vivo in KO mice is attributed to a decrease in growth factor levels in the tissue by the loss of Smad3. PMID:26950486

  3. Morphological patterns of indirect choroidal rupture on spectral domain optical coherence tomography

    PubMed Central

    Nair, Unnikrishnan; Soman, Manoj; Ganekal, Sunil; Batmanabane, Vaishnavi; Nair, KGR

    2013-01-01

    Purpose To evaluate the morphological types of indirect choroidal rupture (ICR) using spectral domain optical coherence tomography (SD-OCT). Methods This was a prospective interventional study of 18 eyes of 18 patients who presented with a history of blunt ocular trauma resulting in choroidal rupture. All patients underwent detailed ophthalmic evaluation and SD-OCT examination. Results Mean age of the patients was 32±9.6 years. Morphologically, two types of choroidal rupture were seen on SD-OCT. The first type seen (Type 1 ICR) was a forward protrusion of the retinal pigment epithelium-choriocapillaris (RPE-CC) layer with an acutely angled pyramid or dome shape. This was associated with either a small loss of continuity of the retinal pigment epithelium layer or elevated RPE-CC projection accompanied by a significant quantity of subretinal hemorrhage. The second type observed (Type 2 ICR) was a larger area of disruption of the RPE-CC layer, photoreceptor inner segment/outer segment junction, and external limiting membrane, with a posteriorly directed concave contour depression at that area and downward sliding of tissues into the defect. At presentation, ten eyes were observed to have Type 1 ICR and eight to have Type 2 ICR. Of the 18 eyes, one with Type 1 ICR and two with Type 2 ICR developed choroidal neovascularization (16.6%). Conclusion Two distinct tomographic patterns of choroidal ruptures were identified on SD-OCT, which may allow ruptures to be classified into two morphological types. There are morphometric and clinical differences between the two types, which may help to prognosticate visual outcome and anticipate complications following choroidal ruptures. PMID:23901259

  4. Choroidal Vascularity Index (CVI) - A Novel Optical Coherence Tomography Parameter for Monitoring Patients with Panuveitis?

    PubMed Central

    Agrawal, Rupesh; Salman, Mohammed; Tan, Kara-Anne; Karampelas, Michael; Sim, Dawn A.; Keane, Pearse A.; Pavesio, Carlos

    2016-01-01

    Purpose To compute choroidal vascularity index (CVI) using an image binarization tool on enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans as a non-invasive optical tool to monitor progression in panuveitis and to investigate the utility of volumetric data from EDI-OCT scans using custom image analysis software. Materials and Methods In this retrospective cohort study, segmented EDI-OCT scans of both eyes in 19 patients with panuveitis were taken at baseline and at 3-month follow-up and were compared with EDI-OCT scans of normal eyes. Subfoveal choroidal area was segmented into luminal (LA) and stromal interstitial area (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to the total circumscribed subfoveal choroidal area (TCA). Results The mean choroidal thickness was 265.5±100.1μm at baseline and 278.4±102.6μm at 3 months follow up (p = 0.06). There was no statistically significant difference in TCA between study and control eyes (p = 0.08). CVI in the control group was 66.9±1.5% at baseline and 66.4±1.5% at follow up. CVI was 74.1±4.7% at baseline and 69.4±4.8% at 3 months follow up for uveitic eyes (p<0.001). The % change in CVI was 6.2 ±3.8 (4.3 to 8.0) for uveitic eyes, which was significantly higher from % change in CVI for control eyes (0.7±1.1, 0.2 to 1.3, p<0.001). Conclusion The study reports composite OCT-derived parameters and CVI as a possible novel tool in monitoring progression in panuveitis. CVI may be further validated in larger studies as a novel optical tool to quantify choroidal vascular status. PMID:26751702

  5. Response of choroidal blood flow to carbogen breathing in smokers and non-smokers

    PubMed Central

    Wimpissinger, B; Resch, H; Berisha, F; Weigert, G; Schmetterer, L; Polak, K

    2004-01-01

    Aim: To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers. Methods: 25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO2 and 95% O2) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters. Results: At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p<0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing. Conclusion: The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised. PMID:15148211

  6. Stimulation of prostanoid IP and EP(2) receptors dilates retinal arterioles and increases retinal and choroidal blood flow in rats.

    PubMed

    Mori, Asami; Saito, Maki; Sakamoto, Kenji; Narita, Masami; Nakahara, Tsutomu; Ishii, Kunio

    2007-09-10

    We examined the effects of vasodilatory prostaglandins (prostacyclin and prostaglandin E(2)) and selective agonists for prostanoid EP(2) and EP(4) receptor on the diameters of retinal blood vessels and fundus (retinal/choroidal) blood flow in rats. Male Wistar rats (8- to 10-week-old) were treated with tetrodotoxin (50 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye and infused with a mixture solution of norepinephrine and epinephrine (1:9) to maintain adequate systemic circulation under artificial ventilation. Fundus images were captured with a digital camera that was equipped with the special objective lens for small animals, and the diameters of retinal arterioles and venules were measured on a personal computer. Fundus blood flow was estimated using a laser Doppler flowmetry. Intravenous infusions of prostacyclin and prostaglandin E(2) dilated retinal blood vessels, increased fundus blood flow and decreased systemic blood pressure in a dose-dependent manner. The effects of vasodilatory prostaglandins on retinal arterioles were greater than those on retinal venules. Similarly, a prostanoid EP(2) receptor agonist (ONO-AE1-259-01) dilated retinal blood vessels, and increased fundus blood flow and decreased systemic blood pressure. However, a prostanoid EP(4) receptor agonist (ONO-AE1-329) failed to increase fundus blood flow, despite its comparable depressor response with those to vasodilatory prostaglandins and the prostanoid EP(2) receptor agonist. The responses to forskolin, an activator of adenylyl cyclase, were very similar to those to prostacyclin and the prostanoid EP(2) receptor agonist. These results suggest that prostacyclin and prostaglandin E(2) act as vasodilators in retinal and choroidal circulation, and prostanoid IP and EP(2) receptors play an important role in the regulation of ocular hemodynamics in rats. PMID:17628525

  7. Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

    PubMed Central

    Liu, Jian; Copland, David A.; Theodoropoulou, Sofia; Chiu, Hsi An Amy; Barba, Miriam Durazo; Mak, Ka Wang; Mack, Matthias; Nicholson, Lindsay B.; Dick, Andrew D.

    2016-01-01

    Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2+ monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development. PMID:26847702

  8. The Small Breathing Amplitude at the Upper Lobes Favors the Attraction of Polymorphonuclear Neutrophils to Mycobacterium tuberculosis Lesions and Helps to Understand the Evolution toward Active Disease in An Individual-Based Model

    PubMed Central

    Cardona, Pere-Joan; Prats, Clara

    2016-01-01

    Infection with Mycobacterium tuberculosis (Mtb) can induce two kinds of lesions, namely proliferative and exudative. The former are based on the presence of macrophages with controlled induction of intragranulomatous necrosis, and are even able to stop its physical progression, thus avoiding the induction of active tuberculosis (TB). In contrast, the most significant characteristic of exudative lesions is their massive infiltration with polymorphonuclear neutrophils (PMNs), which favor enlargement of the lesions and extracellular growth of the bacilli. We have built an individual-based model (IBM) (known as “TBPATCH”) using the NetLogo interface to better understand the progression from Mtb infection to TB. We have tested four main factors previously identified as being able to favor the infiltration of Mtb-infected lesions with PMNs, namely the tolerability of infected macrophages to the bacillary load; the capacity to modulate the Th17 response; the breathing amplitude (BAM) (large or small in the lower and upper lobes respectively), which influences bacillary drainage at the alveoli; and the encapsulation of Mtb-infected lesions by the interlobular septae that structure the pulmonary parenchyma into secondary lobes. Overall, although all the factors analyzed play some role, the small BAM is the major factor determining whether Mtb-infected lesions become exudative, and thus induce TB, thereby helping to understand why this usually takes place in the upper lobes. This information will be very useful for the design of future prophylactic and therapeutic approaches against TB. PMID:27065951

  9. [Collar-button choroidal melanoma. Anatomo-radiologic correlations].

    PubMed

    Berges, O; Cerezal, L; Sterkers, M; Mimoun, G; Piekarski, J D

    1994-03-01

    Malignant melanomas of the choroid are the most frequent symptomatic eye tumours in adults. They often have a pathognomonic appearance, being collar-button or mushroom shaped due to rupture of Bruch's membrane by the tumoral mass. The ultrasonographic image of collar-button melanoma is well known: the head of the tumour is hyperechogenic and its base hypoechogenic. According to some authors, this is caused by difference in blood supply between the two parts. At MRI strongly pigmented melanomas emit a high-intensity signal on T1-weighted sequences and a low-intensity signal on T2-weighted sequences, but these characteristic features are inconstant. We present a case of collar-button melanoma explored by ultrasonography, colour Doppler Flow Imaging (CDFI) ultrasound and MRI, then enucleated. Flows and signals were different in front of, or behind the rupture of Bruch's membrane: ultrasounds showed a hyperechogenic image at the head and a hypoechogenic image at the base; on T2-weighted MRI sections intensity was greater in the head than in the base (head: 69 ms, base 180 ms) on CDFI, no flow was detectable in the head and very high flows were seen in the base of the tumour. Comparisons of these images with pathological findings, where there was no difference between head and base in melanin concentration and in cellular type (mixed or mainly epithelioid), led us to believe that the differences observed in images were essentially due to differences in blood supply between the two parts of the tumour constricted by the sides of the ruptured Bruch's membrane. PMID:8169614

  10. Homeostatic capabilities of the choroid plexus epithelium in Alzheimer's disease

    PubMed Central

    Johanson, Conrad; McMillan, Paul; Tavares, Rosemarie; Spangenberger, Anthony; Duncan, John; Silverberg, Gerald; Stopa, Edward

    2004-01-01

    As the secretory source of vitamins, peptides and hormones for neurons, the choroid plexus (CP) epithelium critically provides substances for brain homeostasis. This distributive process of cerebrospinal fluid (CSF) volume transmission reaches many cellular targets in the CNS. In ageing and ageing-related dementias, the CP-CSF system is less able to regulate brain interstitial fluid. CP primarily generates CSF bulk flow, and so its malfunctioning exacerbates Alzheimers disease (AD). Considerable attention has been devoted to the blood-brain barrier in AD, but more insight is needed on regulatory systems at the human blood-CSF barrier in order to improve epithelial function in severe disease. Using autopsied CP specimens from AD patients, we immunocytochemically examined expression of heat shock proteins (HSP90 and GRP94), fibroblast growth factor receptors (FGFr) and a fluid-regulatory protein (NaK2Cl cotransporter isoform 1 or NKCC1). CP upregulated HSP90, FGFr and NKCC1, even in end-stage AD. These CP adjustments involve growth factors and neuropeptides that help to buffer perturbations in CNS water balance and metabolism. They shed light on CP-CSF system responses to ventriculomegaly and the altered intracranial pressure that occurs in AD and normal pressure hydrocephalus. The ability of injured CP to express key regulatory proteins even at Braak stage V/VI, points to plasticity and function that may be boosted by drug treatment to expedite CSF dynamics. The enhanced expression of human CP 'homeostatic proteins' in AD dementia is discussed in relation to brain deficits and pharmacology. PMID:15679944

  11. Successful treatment of melanocytoma associated choroidal neovascular membrane with intravitreal bevacizumab.

    PubMed

    Al-Halafi, Ali M

    2013-04-01

    Melanocytoma of the optic disc is a benign melanocytic tumour that rarely causes visual impairment. We report a rare case of choroidal neovascularization (CNV) in association with optic disc melanocytoma and its response to intravitreal injection of the anti-vascular endothelial growth factor (VEGF), bevacizumab. The choroidal neovascular membrane regressed following a single intravitreal bevacizumab injection with formation of a scar. CNV associated with optic disc melanocytoma is rare. Intravitreal anti-VEGF treatment may be an effective treatment for CNV associated with optic disc melanocytoma. PMID:24227972

  12. Example based lesion segmentation

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; He, Qing; Carass, Aaron; Jog, Amod; Cuzzocreo, Jennifer L.; Reich, Daniel S.; Prince, Jerry; Pham, Dzung

    2014-03-01

    Automatic and accurate detection of white matter lesions is a significant step toward understanding the progression of many diseases, like Alzheimer's disease or multiple sclerosis. Multi-modal MR images are often used to segment T2 white matter lesions that can represent regions of demyelination or ischemia. Some automated lesion segmentation methods describe the lesion intensities using generative models, and then classify the lesions with some combination of heuristics and cost minimization. In contrast, we propose a patch-based method, in which lesions are found using examples from an atlas containing multi-modal MR images and corresponding manual delineations of lesions. Patches from subject MR images are matched to patches from the atlas and lesion memberships are found based on patch similarity weights. We experiment on 43 subjects with MS, whose scans show various levels of lesion-load. We demonstrate significant improvement in Dice coefficient and total lesion volume compared to a state of the art model-based lesion segmentation method, indicating more accurate delineation of lesions.

  13. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents.

    PubMed

    Olatunji, Opeyemi J; Chen, Hongxia; Zhou, Yifeng

    2015-01-01

    The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers. PMID:26694339

  14. Peripherally administered tetrahydrobiopterin increases in vivo tryptophan hydroxylase activity in the striatum after transplantation of fetal ventral mesencephalon in six hydroxydopamine lesioned rats.

    PubMed

    Ishida, Y; Todaka, K; Kuwahara, I; Hashiguchi, H; Ishizuka, Y; Nakane, H; Mitsuyama, Y

    1998-08-28

    The intraperitoneal administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4), a natural cofactor for tyrosine hydroxylase and tryptophan hydroxylase (TRH), dose-dependently increased the extracellular concentration of 6R-BH4 itself in rat striatum. The concentration was investigated by in vivo microdialysis and measured simultaneously with 5-hydroxytryptophan (5-HTP), a precursor of serotonin, by high performance liquid chromatography with electrochemical detection. The 6R-BH4 (50 mg/kg, i.p.) administration increased the accumulation of 5-HTP as an index of in vivo TRH activity under the inhibition of aromatic L-amino acid decarboxylase by NSD-1015 in the striatum of both normal control and 6-hydroxydopamine lesioned rats with intrastriatal transplants of fetal ventral mesencephalon (VM). The results suggest that TRH in the striatum of both control and VM-grafted rats is activated by 6R-BH4 penetrating into the brain from the blood. PMID:9754801

  15. Activity of citrus canker lesions on leaves, shoots and fruit of grapefruit in a Florida orchard from June 2010 to January 2011

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lesions of citrus canker, caused by Xanthomonas citri subsp. citri (Xcc), on citrus fruit preclude export to certain markets. Characterizing the population dynamics of bacteria in canker lesions in commercial orchards can help gauge risk associated with diseased fruit entering fresh markets. The aim...

  16. Increased HIV-1 activity in anal high-grade squamous intraepithelial lesions compared with unaffected anal mucosa in men who have sex with men.

    PubMed

    Pollakis, Georgios; Richel, Olivier; Vis, Joost D; Prins, Jan M; Paxton, William A; de Vries, Henry J C

    2014-06-01

    We studied 3 patients with focal intra-anal tissue high-grade squamous intraepithelial lesions (HSILs). All had increased human immunodeficiency virus type 1 (HIV-1) RNA and DNA in lesions compared with that in healthy mucosa. HIV-1 RNA and HIV-1 episomal DNA were indicative of ongoing viral replication, more so in anal HSILs. PMID:24604897

  17. Histopathology and ultrastructure of ocular lesions associated with gas bubble disease in salmonids.

    PubMed

    Speare, D J

    1990-11-01

    Ocular lesions associated with natural and experimental outbreaks of gas bubble disease (GBD) in commercial salmonids were assessed histologically and by scanning electron microscopy. Small gas emboli were first detected in the choroid gland of the posterior uvea. In subacute and chronic cases, bubble size increased markedly and localization in retrobulbar and periocular sites was favoured. During the acute phase of GBD, ocular lesions were limited to anatomical displacement of tissue and local degeneration of compressed tissues around the perimeter of bubbles. Subacute sequelae included the formation of anterior synechia, lens cataract, and suppurative panophthalmitis. During chronic stages, when large retrobulbar bubbles had caused severe exophthalmia, there was stretching of the optic nerve and of retinal blood vessels and severe distortion of the posterior aspects of the globe. The sequential development, pathogenesis and persistence of ocular lesions associated with GBD in fish are discussed. PMID:2079557

  18. Multiple isoforms of the tumor protein p73 are expressed in the adult human telencephalon and choroid plexus and present in the cerebrospinal fluid.

    PubMed

    Cabrera-Socorro, Alfredo; Pueyo Morlans, Mercedes; Suarez Sola, Maria Luisa; Gonzalez Delgado, Francisco J; Castañeyra-Perdomo, Agustin; Marin, Maria C; Meyer, Gundela

    2006-04-01

    p73, a homolog of the p53 tumor suppressor, codes for full-length transactivating (TA) and N-terminally truncated (DeltaN) isoforms, with pro- and anti-apoptotic activities, respectively. We examined the expression of the main p73 isoforms in adult human and mouse telencephalon and choroid plexus by immunohistochemistry on paraffin sections, and immunoblotting (IB) of tissue extracts and cerebrospinal fluid (CSF), using antibodies against different protein domains. Cortical neurons expressed TAp73 predominantly in the cytoplasm and DeltaNp73 mainly in the nucleus, with partial overlap in the cytoplasm. Highest expression was found in the hippocampus. IB showed an array of TAp73 variants in adult human cortex and hippocampus. IB of human choroid plexus and CSF using TAp73-specific antibodies revealed the presence of a approximately 90-kDa protein whose molecular weight was reduced after N-deglycosylation, suggesting that glycosylated TAp73 is exported into the CSF. In the mouse, high expression of TAp73 was also detected in the subcommissural organ (SCO), an ependymal gland absent in adult humans. TAp73 colocalized with anti-fibra-Reissner-antibody (AFRU), which is a marker of Reissner's fiber, the secreted SCO product. p73-deficient mice had generalized cortical hypoplasia and hydrocephalus; in addition, we observed a dramatic size reduction of the choroid plexus. However, the SCOs were apparently unaltered and continued to secrete Reissner's fiber. Our findings point to complex and widespread p73 activities in the maintenance of adult cortical neurons and in brain homeostasis. TAp73 in the CSF may play important roles in the maintenance of the adult ventricular wall as well as in the development of the proliferating neuroepithelium. PMID:16630058

  19. Histopathology of diode and argon laser lesions in rabbit retina. A comparative study

    SciTech Connect

    Brancato, R.; Pratesi, R.; Leoni, G.; Trabucchi, G.; Vanni, U.

    1989-07-01

    Argon lasers are the most frequently used laser source for retinal photocoagulation. These are expensive, bulky and low-efficiency devices. In contrast, diode semiconductor lasers have a number of characteristics that make them attractive for medical application: compact size, high electrical-to-optical efficiency, and long operating lifetime. Comparable irradiance lesions (about 120 Wcm2), ophthalmoscopically similar to those obtained therapeutically in humans, were obtained by a diode and an argon laser. Twenty-four hours after the treatment, a study of these lesions was made by light and electron microscopy. Argon irradiations resulted in damage to both the inner and the outer retinal layers, while the diode laser radiation produced damage to the outer retina and choroid. A sufficient diode laser light passed into the choroid to induce small vessel occlusions and/or edema. The histological characteristics of the lesions produced by the two lasers suggest the use of the diode lasers, as well as argon lasers, in the treatment of retinal and subretinal pathologies.