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Sample records for pigment epithelium lesions

  1. Detachments of the retinal pigment epithelium at the posterior pole.

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    Noble, K G; Levitzky, M J; Carr, R E

    1976-08-01

    Multiple vitelliform cysts of the retina, a disorder of unknown cause in which there are multiple detachments of the retinal pigment epithelium at the posterior pole, occurred in five patients. In four patients all lesions were located outside the parafoveal area while one patient showed bilateral foveal elevations associated with more eccentric detachments. Several patients showed slow resolution of some of the detachments with mild disturbances of the pigment epithelium.

  2. Down-regulation of pigment epithelium-derived factor in uveitic lesion associates with focal vascular endothelial growth factor expression and breakdown of the blood-retinal barrier.

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    Deeg, Cornelia A; Altmann, Frank; Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Ueffing, Marius

    2007-05-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Identifying biological markers or pathways associated with this disease may allow the understanding of its pathogenesis at a molecular level. The vitreous is the body fluid closest to the disease-affected tissue and possibly also an effector of pathological processes relevant for ERU. Surgical removal of vitreous leads to cessation of relapses in spontaneous uveitis of both man and horse, therefore vitreous composites are likely to contribute to disease progression. Uveitic vitreous is likely to contain potential biomarkers in relatively undiluted quantities. With the goal to identify these markers, we systematically compared vitreous from healthy and disease-affected eyes by proteomic profiling. Nine differentially expressed proteins were identified, that are functionally related to immune response, inflammation, and maintenance of the blood-retinal barrier. One of these, pigment epithelium-derived factor, a protein involved in maintaining a proper blood-retina barrier as well as protecting from neoangiogenesis was additionally found to be down-regulated within uveitic retinal lesions whereas, conversely, vascular endothelial growth factor was found to be up-regulated at these sites. Together, these changes point to as of yet undiscovered biological pathways involved in the pathogenesis of this autoimmune disease.

  3. Comparison of antioxidation systems of retinal pigment epithelium of pigmented and albino animals

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    Sakina, N.L.; Dontsov, A.E.; Ostrovskiy, M.A.

    1985-01-01

    The effectiveness of the lipid peroxidation inhibition process by tissue homogenates of retinal pigment epithelium of pigmented rabbits is higher than that of albino rabbits. The superoxide dismutase and glutathione perioxidase activity is nearly the same in both tissues of the pigment epithelium, the ..cap alpha..-tocopherol content is higher in retinal pigment epithelium tissue of albino animals, and the oxidizability of the lipid fraction of pigment epithelium tissue is higher in pigmented animals than in albinos. It is concluded that the higher resistance of the pigment epithelium of pigmented animals to the effects of prooxidant systems is due to the presence of melanoprotein granules in the pigment epithelium.

  4. Neoplasia versus hyperplasia of the retinal pigment epithelium

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    Heegaard, Steffen; Larsen, J.N.B.; Fledelius, Hans C.

    2001-01-01

    ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography......ophthalmology, retinal pigment epithelium, adenoma, tumor-like hyperplasia, histology, immunohistochemistry, tumor, neoplasm, ultrasonography...

  5. Glucose metabolism in rat retinal pigment epithelium.

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    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  6. Culturing of retinal pigment epithelium cells.

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    Valtink, Monika; Engelmann, Katrin

    2009-01-01

    The retinal pigment epithelium (RPE) is a monolayer of cells adjacent to the photoreceptors of the retina. It plays a crucial role in maintaining photoreceptor health and survival. Degeneration or dysfunction of the RPE can lead to photoreceptor degeneration and as a consequence to visual impairment. The most common diseased state of the RPE becomes manifest in age-related macular degeneration, an increasing cause of blindness in the elderly. RPE cells are therefore of great interest to researchers working in the field of tissue engineering and cell transplantation. In fact, studies in animal models have proven that the transplantation of RPE cells can delay the course of photoreceptor degenerative diseases. Although first attempts to transplant RPE cells into the subretinal space in human individuals suffering from age-related macular degeneration were less successful, RPE cell transplantation is still favored as a future therapeutic option, and much work is done to develop and design cell transplants. Cell banking is a prerequisite to have well-differentiated and characterized cells at hand when needed for research purposes, but also for therapeutic approaches. In this chapter the authors will describe methods to isolate, culture and preserve adult human RPE cells for the purpose of RPE cell banking. Copyright 2009 S. Karger AG, Basel.

  7. The clinical spectrum of pigmented lesions.

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    Schaffer, J V; Bolognia, J L

    2000-07-01

    This article presents the clinical features of a spectrum of pigmented lesions. It begins with benign lesions that may be confused with melanocytic nevi, such as lentigines, seborrheic keratoses, and dermatofibromas. The next section focuses on the various types of melanocytic nevi, including congenital, blue, and Spitz nevi. A description of atypical nevi is provided, followed by an outline of the clinical characteristics of each subtype of cutaneous melanoma. The clinical characteristics of various pigmented lesions are illustrated.

  8. Functional annotation of the human retinal pigment epithelium transcriptome

    NARCIS (Netherlands)

    J.C. Booij (Judith); S. van Soest (Simone); S.M.A. Swagemakers (Sigrid); A.H.W. Essing (Anke); J.H.M. Verkerk (Annemieke); P.J. van der Spek (Peter); T.G.M.F. Gorgels (Theo); A.A.B. Bergen (Arthur)

    2009-01-01

    textabstractBackground: To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy

  9. Functional annotation of the human retinal pigment epithelium transcriptome

    NARCIS (Netherlands)

    Booij, J.C.; van Soest, S.; Swagemakers, S.M.A.; Essing, A.H.W.; Verkerk, A.J.M.H.; van der Spek, P.J.; Gorgels, T.G.M.F.; Bergen, A.A.B.

    2009-01-01

    ABSTRACT: BACKGROUND: To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE), the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy hu

  10. Developmental origin of the posterior pigmented epithelium of iris.

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    Wang, Xiaobing; Xiong, Kai; Lu, Lei; Gu, Dandan; Wang, Songtao; Chen, Jing; Xiao, Honglei; Zhou, Guomin

    2015-03-01

    Iris epithelium is a double-layered pigmented cuboidal epithelium. According to the current model, the neural retina and the posterior iris pigment epithelium (IPE) are derived from the inner wall of the optic cup, while the retinal pigment epithelium (RPE) and the anterior IPE are derived from the outer wall of the optic cup during development. Our current study shows evidence, contradicting this model of fetal iris development. We demonstrate that human fetal iris expression patterns of Otx2 and Mitf transcription factors are similar, while the expressions of Otx2 and Sox2 are complementary. Furthermore, IPE and RPE exhibit identical morphologic development during the early embryonic period. Our results suggest that the outer layer of the optic cup forms two layers of the iris epithelium, and the posterior IPE is the inward-curling anterior rim of the outer layer of the optic cup. These findings provide a reasonable explanation of how IPE cells can be used as an appropriate substitute for RPE cells.

  11. Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill

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    González, Alfredo; Crittenden, Elizabeth L; García, Dana M

    2004-01-01

    Background In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. Results The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl) carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Conclusions Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion. PMID:15251036

  12. Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegill

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    Crittenden Elizabeth L

    2004-07-01

    Full Text Available Abstract Background In fish, melanin pigment granules in the retinal pigment epithelium disperse into apical projections as part of the suite of responses the eye makes to bright light conditions. This pigment granule dispersion serves to reduce photobleaching and occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine may be involved in inducing light-adaptive pigment dispersion. Acetylcholine receptors are of two main types, nicotinic and muscarinic. Muscarinic receptors are in the G-protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. These receptors are coupled to adenylyl cyclase, calcium mobilization and ion channel activation. To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents. Results The general cholinergic agonist carbachol induces pigment granule dispersion in isolated retinal pigment epithelium. Carbachol-induced pigment granule dispersion is blocked by the muscarinic antagonist atropine, by the M1 antagonist pirenzepine, and by the M3 antagonist 4-DAMP. Pigment granule dispersion was also induced by the M1 agonist 4-[N-(4-chlorophenyl carbamoyloxy]-4-pent-2-ammonium iodide. In contrast the M2 antagonist AF-DX 116 and the M4 antagonist tropicamide failed to block carbachol-induced dispersion, and the M2 agonist arecaidine but-2-ynyl ester tosylate failed to elicit dispersion. Conclusions Our results suggest that carbachol-mediated pigment granule dispersion occurs through the activation of Modd muscarinic receptors, which in other systems couple to phosphoinositide hydrolysis and elevation of intracellular calcium. This conclusion must be corroborated by molecular studies, but suggests Ca2+-dependent pathways may be involved in light-adaptive pigment dispersion.

  13. Dermoscopic Features of Facial Pigmented Skin Lesions

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    Goncharova, Yana; Attia, Enas A. S.; Souid, Khawla; Vasilenko, Inna V.

    2013-01-01

    Four types of facial pigmented skin lesions (FPSLs) constitute diagnostic challenge to dermatologists; early seborrheic keratosis (SK), pigmented actinic keratosis (AK), lentigo maligna (LM), and solar lentigo (SL). A retrospective analysis of dermoscopic images of histopathologically diagnosed clinically-challenging 64 flat FPSLs was conducted to establish the dermoscopic findings corresponding to each of SK, pigmented AK, LM, and SL. Four main dermoscopic features were evaluated: sharp demarcation, pigment pattern, follicular/epidermal pattern, and vascular pattern. In SK, the most specific dermoscopic features are follicular/epidermal pattern (cerebriform pattern; 100% of lesions, milia-like cysts; 50%, and comedo-like openings; 37.50%), and sharp demarcation (54.17%). AK and LM showed a composite characteristic pattern named “strawberry pattern” in 41.18% and 25% of lesions respectively, characterized by a background erythema and red pseudo-network, associated with prominent follicular openings surrounded by a white halo. However, in LM “strawberry pattern” is widely covered by psewdonetwork (87.5%), homogenous structureless pigmentation (75%) and other vascular patterns. In SL, structureless homogenous pigmentation was recognized in all lesions (100%). From the above mentioned data, we developed an algorithm to guide in dermoscopic features of FPSLs. PMID:23431466

  14. [Macroadenoma of the non-pigmented ciliary epithelium].

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    Lara-Medina, J; Ispa Callén, C; González del Valle, F; Mate Valdezate, A

    2014-06-01

    We report the clinical features and surgery of a patient with an adenoma of the non-pigmented ciliary epithelium. The adenoma measured 5 × 7 mm. The patient underwent radical ocular surgery consisting of partial iridocyclectomy associated to lamellar sclerouvectomy. Adenomas of ciliary body can mimic clinically amelanotic melanomas. We present details of the patient's medical records and review the literature. Clinically, adenoma in ciliary body can mimic amelanotic melanomas. Conservative surgery of the eye allows diagnosis and treatment, maintaining visual function. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  15. Druse-Induced Morphology Evolution in Retinal Pigment Epithelium

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    Mazzitello, K I; Chrenek, M A; Family, F; Grossniklaus, H E; Nickerson, J M; Jiang, Y

    2016-01-01

    The retinal pigment epithelium (RPE) is a key site of pathogenesis for many retina diseases. The formation of drusen in the retina is characteristic of retinal degeneration. We investigate morphological changes in the RPE in the presence of soft drusen using an integrated experimental and modeling approach. We collect RPE flat mount images from donated human eyes and develop 1) statistical tools to quantify the images and 2) a cell-based model to simulate the morphology evolution. We compare three different mechanisms of RPE repair evolution, cell apoptosis, cell fusion, and expansion, and Simulations of our RPE morphogenesis model quantitatively reproduce deformations of human RPE morphology due to drusen, suggesting that a purse-string mechanism is sufficient to explain how RPE heals cell loss caused by drusen-damage. We found that drusen beneath tissue promote cell death in a number that far exceeds the cell numbers covering the drusen. Tissue deformations are studied using area distributions, Voronoi doma...

  16. Optical modulation of transgene expression in retinal pigment epithelium

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    Palanker, D.; Lavinsky, D.; Chalberg, T.; Mandel, Y.; Huie, P.; Dalal, R.; Marmor, M.

    2013-03-01

    Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a "biofactory" that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

  17. Zinc deficiency leads to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats.

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    Sylvie Julien

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. METHODOLOGY/PRINCIPAL FINDINGS: Adult Long Evans (LE rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE. The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. CONCLUSIONS/SIGNIFICANCE: In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.

  18. Functional annotation of the human retinal pigment epithelium transcriptome

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    Gorgels Theo GMF

    2009-04-01

    Full Text Available Abstract Background To determine level, variability and functional annotation of gene expression of the human retinal pigment epithelium (RPE, the key tissue involved in retinal diseases like age-related macular degeneration and retinitis pigmentosa. Macular RPE cells from six selected healthy human donor eyes (aged 63–78 years were laser dissected and used for 22k microarray studies (Agilent technologies. Data were analyzed with Rosetta Resolver, the web tool DAVID and Ingenuity software. Results In total, we identified 19,746 array entries with significant expression in the RPE. Gene expression was analyzed according to expression levels, interindividual variability and functionality. A group of highly (n = 2,194 expressed RPE genes showed an overrepresentation of genes of the oxidative phosphorylation, ATP synthesis and ribosome pathways. In the group of moderately expressed genes (n = 8,776 genes of the phosphatidylinositol signaling system and aminosugars metabolism were overrepresented. As expected, the top 10 percent (n = 2,194 of genes with the highest interindividual differences in expression showed functional overrepresentation of the complement cascade, essential in inflammation in age-related macular degeneration, and other signaling pathways. Surprisingly, this same category also includes the genes involved in Bruch's membrane (BM composition. Among the top 10 percent of genes with low interindividual differences, there was an overrepresentation of genes involved in local glycosaminoglycan turnover. Conclusion Our study expands current knowledge of the RPE transcriptome by assigning new genes, and adding data about expression level and interindividual variation. Functional annotation suggests that the RPE has high levels of protein synthesis, strong energy demands, and is exposed to high levels of oxidative stress and a variable degree of inflammation. Our data sheds new light on the molecular composition of BM, adjacent to the

  19. Laser therapy of pigmented lesions: pro and contra.

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    Bukvić Mokos, Zrinka; Lipozenčić, Jasna; Ceović, Romana; Stulhofer Buzina, Daška; Kostović, Krešimir

    2010-01-01

    Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory.

  20. Infection of Human Retinal Pigment Epithelium with Chlamydia trachomatis.

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    Ernest Boiko

    Full Text Available Little is known about the susceptibility of posterior segment tissues, particularly the human retinal pigment epithelium (hRPE, to Chlamydia trachomatis. The purpose of the study was to investigate the possibility of infecting the hRPE with Chlamydia trachomatis, and to examine the infectivity of different Chlamydia trachomatis clinical isolates for hRPE cells and the hRPE cell response to the infection.Cultured hRPE and McCoy cells were inoculated with eight Chlamydia trachomatis (serovar E clinical isolates at multiplicity of infection (MOI of 2.0 or 0.3. To detect Chlamydia trachomatis, samples were stained immunohistochemically with anti-major outer membrane protein antibodies at 24h, 48h, and 72h postinoculation (PI. The changes in the expression of signaling molecules and proteins of cytoskeleton and extracellular matrix in hRPE cells were examined immunohistochemically.All eight clinical isolates demonstrated ability to infect hRPE cells. At equal MOI of 0.3, the infectivity of Chlamydia trachomatis clinical isolates for RPE culture was found to be at least as high as that for McCoy cell culture. At 24h PI, the percentage of inclusion-containing cells varied from 1.5 ± 0.52 to 14.6 ± 3.3% in hRPE cell culture infected at MOI of 2.0 against 0.37 ± 0.34 to 8.9 ± 0.2% in McCoy cell culture infected at MOI of 0.3. Collagen type I, collagen type IV, basic fibroblast growth factor, transforming growth factor-beta and interleukin-8 expression at 48h PI were maximally increased, by 2.1-, 1.3-, 1.5-, 1.5- and 1.6-fold, respectively, in the Chlamydia trachomatis-infected compared with control hRPE cell culture specimens (P < 0.05.This study, for the first time, proved the possibility of infecting hRPE cultured cells with Chlamydia trachomatis, which leads to proproliferative and proinflammatory changes in the expression of signaling molecules and extracellular matrix components.

  1. Pathological, Ultrastructural and Immunohistochemical Observations of Adenoma of Retinal Pigment Epithelium

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    Ping Zhang; Guanguang Feng; Tao Yue; Jianxian Lin; Yuzhen Yi; Youjian Pang

    2001-01-01

    Purpose: To Study the clinical, pathological, ultrastructural and immunohistchemicalcharacters of adenoma of the retinal pigment epithelium in order to offer evidence todiagnose this tumor.Methods: Routine paraffin slices HE stain, histochemistry PAS and VG stain,transmission electron microscopy, and immunohistochemistry for S-100 and vimentinwith LSAB method were used.Results: The tumor cells were oval and cuboidal in shape. Part of the tumor had atubular arrangement. Around the sheets of tumors cells there was a large amount ofuniform red stick-like substances. The above matter represented positive in PAS stain.Most of the above matter was yellow, while less of the matter showed red in VG stain.Transmission electron microscopy showed that there were tight junctions between tumorcells. Immunohistochemistry showed positive for S-100, negative for vimentin.Conclusions: The ultrastructural and immunohistochemical characters of the adenoma ofretinal pigment epithelium are consistent with the retinal pigment epithelium.

  2. Surgical treatment in combined hamartoma of the retina and retinal pigment epithelium.

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    Sánchez-Vicente, J L; Rueda-Rueda, T; Llerena-Manzorro, L; Molina-Socola, F E; Contreras-Díaz, M; Szewc, M; Vital-Berral, C; Alfaro-Juárez, A; Medina-Tapia, A; López-Herrero, F; González-García, L; Muñoz-Morales, A

    2017-03-01

    The case is presented of a 39 year-old man with a combined hamartoma of the retina and retinal pigment epithelium, who experienced progressive visual loss and worsening of metamorphopsia. The patient underwent vitrectomy and epiretinal component peeling, with improvement in visual acuity, metamorphopsia, and retinal architecture, assessed by optical coherence tomography. Selected patients with combined hamartomas of the retina and retinal pigment epithelium may benefit from surgical management. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

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    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  4. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  5. Retinal Pigment Epithelium Cell Alignment on Nanostructured Collagen Matrices

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    Ulbrich, Stefan; Friedrichs, Jens; Valtink, Monika; Murovski, Simo; Franz, Clemens M.; Müller, Daniel J.; Richard H. W. Funk; Engelmann, Katrin

    2014-01-01

    We investigated attachment and migration of human retinal pigment epithelial cells (primary, SV40-transfected and ARPE-19) on nanoscopically defined, two-dimensional matrices composed of parallel-aligned collagen type I fibrils. These matrices were used non-cross-linked (native) or after riboflavin/UV-A cross-linking to study cell attachment and migration by time-lapse video microscopy. Expression of collagen type I and IV, MMP-2 and of the collagen-binding integrin subunit α2 were examined b...

  6. Predictive value of exfoliative cytology in pigmented conjunctival lesions.

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    Keijser, Sander; van Luijk, Chantal M; Missotten, Guy S; Veselic-Charvat, Maud; de Wolff-Rouendaal, Didi; de Keizer, Rob J W

    2006-04-01

    Pigmented lesions of the conjunctiva are often difficult to classify clinically. Exfoliative cytology may be helpful, but reliable data regarding the sensitivity and specificity of this test are currently lacking. We determined the value of exfoliative cytology with regard to pigmented conjunctival lesions. A total of 294 smears from 182 patients were screened for malignancy within 6 months of exfoliative cytology. Smears were classified according to the following categories: grade 0 = insufficient material for diagnosis; grade 1 = normal conjunctival cells; grade 2 = melanocytes with mild atypia; grade 3 = melanocytes with moderate atypia, and grade 4 = melanocytes with severe atypia. The sensitivity, specificity, positive predictive value and negative predictive value of exfoliative cytology were 85%, 78%, 59% and 93%, respectively. Exfoliative cytology is a fast, easy and non-invasive technique that may be used in the evaluation of patients with a pigmented conjunctival lesion.

  7. Spectrophotometric intracutaneous analysis for differential diagnosis of pigmented skin lesions

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    Е. V. Filonenko

    2013-01-01

    Full Text Available The non-invasive diagnosis of pigmented skin lesions by spectrophotometric intracutaneous analysis (SIA-scopy using device for dermatoscopy (SIAscope V by Astron Clinica, Ltd was approved in P.A.Herzen Moscow Cancer Research Institute. The method is based on analysis of light interaction with wavelength of 440–960 nm anf human skin, which is recorded by change of image on scan. The comparative analysis of SIA-scopy and histological data in 327 pigmented skin lesions in 147 patients showed, that SIA had high diagnostic efficiency for cutaneous melanoma: the sensitivity was 96%, specifity – 94%, diagnostic accuracy – 94%. For study of malignant potential of pigmented lesions by SIA-scopy the most informative capacity was obtained for assessment of melanin in papillary dermis, status of blood vessels and collagen fibres (SIA-scans 3, 4, 5.

  8. Standard guidelines of care: Lasers for tattoos and pigmented lesions

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    Aurangabadkar Sanjeev

    2009-08-01

    Full Text Available Introduction: Lasers have revolutionized the treatment of pigmentary disorders and have become the mainstay of therapy for many of them. Machines: Though different laser machines are used, Quality-switched (QS lasers are considered as the gold standard for treatment of pigmented lesions. Proper knowledge of the physics of laser machine, methodology, dosage schedules, etc., is mandatory. Physician Qualification: Laser may be administered by a dermatologist, who has received adequate background training in lasers during postgraduation or later at a center that provides education and training in lasers, or in focused workshops which provide such trainings. He should have adequate knowledge of the machines, parameters, cooling systems, and aftercare. Facility: The procedure may be performed in the physician′s minor procedure room. Indications: Epidermal lesions: Cafι au lait macules (CALM, lentigines, freckles, solar lentigo, nevus spilus, pigmented seborrheic keratosis, dermatosis papulosa nigra (DPN. Dermal lesions: Nevus of Ota, Blue nevus, Hori′s nevus (acquired bilateral nevus of Ota-like macules. Tattoos: Amateur, professional, cosmetic, medicinal, and traumatic. Mixed epidermal and dermal lesions: Postinflammatory hyperpigmentation (PIH, nevus spilus, periorbital and perioral pigmentation, acquired melanocytic nevi (moles, melasma and Becker′s Nevus. Contraindications: Absolute: Active local infection, photo-aggravated skin diseases and medical conditions, tattoo granuloma, allergic reactions to tattoo pigment, unstable vitiligo and psoriasis. Relative: Keloid and keloidal tendencies, patient on isotretinoin, history of herpes simplex, patient who is not co-operative or has unrealistic expectation. Patient selection: Proper patient selection is important. Investigations to identify any underlying cause for pigmentation are important; concurrent topical and systemic drug therapy may be needed. History of scarring, response to previous

  9. In vitro differentiation of retinal pigment epithelium from adult retinal stem cells.

    Science.gov (United States)

    Aruta, Claudia; Giordano, Francesca; De Marzo, Anna; Comitato, Antonella; Raposo, Graça; Nandrot, Emeline F; Marigo, Valeria

    2011-02-01

    One of the limitations in molecular and functional studies of the retinal pigment epithelium (RPE) has been the lack of an in vitro system retaining all the features of in vivo RPE cells. Retinal pigment epithelium cell lines do not show characteristics typical of a functional RPE, such as pigmentation and expression of specific markers. The present study was aimed at the development of culture conditions to differentiate, in vitro, retinal stem cells (RSC), derived from the adult ciliary body, into a functional RPE. Retinal stem cells were purified from murine eyes, grown as pigmented neurospheres and induced to differentiate into RPE on an extracellular matrix substrate using specific culture conditions. After 7-15 days of culture, pigmented cells with an epithelial morphology showed a polarized organization and a capacity for phagocytosis. We detected different stages of melanogenesis in cells at 7 days of differentiation, whereas RPE at 15 days contained only mature melanosomes. These data suggest that our protocol to differentiate RPE in vitro can provide a useful model for molecular and functional studies.

  10. Retinoic acid from retinal pigment epithelium induces T regulatory cells.

    Science.gov (United States)

    Kawazoe, Yuko; Sugita, Sunao; Keino, Hiroshi; Yamada, Yukiko; Imai, Ayano; Horie, Shintaro; Mochizuki, Manabu

    2012-01-01

    Primary cultured retinal pigment epithelial (RPE) cells can convert T cells into T regulatory cells (Tregs) through inhibitory factor(s) including transforming growth factor β (TGFβ) in vitro. Retinoic acid (RA) enhances induction of CD4(+) Tregs in the presence of TGFβ. We investigated whether RA produced by RPE cells can promote generation of Tregs. We found that in vitro, RA-treated T cells expressed high levels of Foxp3 in the presence of recombinant TGFβ. In GeneChip analysis, cultured RPE cells constitutively expressed RA-associated molecules such as RA-binding proteins, enzymes, and receptors. RPE from normal mice, but not vitamin A-deficient mice, contained significant levels of TGFβ. RPE-induced Tregs from vitamin A-deficient mice failed to suppress activation of target T cells. Only a few Foxp3(+) T cells were found in intraocular cells from vitamin A-deficient experimental autoimmune uveitis (EAU) mice, whereas expression was higher in cells from normal EAU mice. RA receptor antagonist-pretreated or RA-binding protein-siRNA-transfected RPE cells failed to convert CD4(+) T cells into Tregs. Our data support the hypothesis that RPE cells produce RA, thereby enabling bystander T cells to be converted into Tregs through TGFβ promotion, which can then participate in the establishment of immune tolerance in the eye.

  11. The retinal pigment epithelium utilizes fatty acids for ketogenesis.

    Science.gov (United States)

    Adijanto, Jeffrey; Du, Jianhai; Moffat, Cynthia; Seifert, Erin L; Hurle, James B; Philp, Nancy J

    2014-07-25

    Every day, shortly after light onset, photoreceptor cells shed approximately a tenth of their outer segment. The adjacent retinal pigment epithelial (RPE) cells phagocytize and digest shed photoreceptor outer segment, which provides a rich source of fatty acids that could be utilized as an energy substrate. From a microarray analysis, we found that RPE cells express particularly high levels of the mitochondrial HMG-CoA synthase 2 (Hmgcs2) compared with all other tissues (except the liver and colon), leading to the hypothesis that RPE cells, like hepatocytes, can produce β-hydroxybutyrate (β-HB) from fatty acids. Using primary human fetal RPE (hfRPE) cells cultured on Transwell filters with separate apical and basal chambers, we demonstrate that hfRPE cells can metabolize palmitate, a saturated fatty acid that constitutes .15% of all lipids in the photoreceptor outer segment, to produce β-HB. Importantly, we found that hfRPE cells preferentially release β-HB into the apical chamber and that this process is mediated primarily by monocarboxylate transporter isoform 1 (MCT1). Using a GC-MS analysis of (13)C-labeled metabolites, we showed that retinal cells can take up and metabolize (13)C-labeled β-HB into various TCA cycle intermediates and amino acids. Collectively, our data support a novel mechanism of RPE-retina metabolic coupling in which RPE cells metabolize fatty acids to produce β-HB, which is transported to the retina for use as a metabolic substrate.

  12. Retinal pigment epithelium cell alignment on nanostructured collagen matrices.

    Science.gov (United States)

    Ulbrich, Stefan; Friedrichs, Jens; Valtink, Monika; Murovski, Simo; Franz, Clemens M; Müller, Daniel J; Funk, Richard H W; Engelmann, Katrin

    2011-01-01

    We investigated attachment and migration of human retinal pigment epithelial cells (primary, SV40-transfected and ARPE-19) on nanoscopically defined, two-dimensional matrices composed of parallel-aligned collagen type I fibrils. These matrices were used non-cross-linked (native) or after riboflavin/UV-A cross-linking to study cell attachment and migration by time-lapse video microscopy. Expression of collagen type I and IV, MMP-2 and of the collagen-binding integrin subunit α(2) were examined by immunofluorescence and Western blotting. SV40-RPE cells quickly attached to the nanostructured collagen matrices and aligned along the collagen fibrils. However, they disrupted both native and cross-linked collagen matrices within 5 h. Primary RPE cells aligned more slowly without destroying either native or cross-linked substrates. Compared to primary RPE cells, ARPE-19 cells showed reduced alignment but partially disrupted the matrices within 20 h after seeding. Expression of the collagen type I-binding integrin subunit α(2) was highest in SV40-RPE cells, lower in primary RPE cells and almost undetectable in ARPE-19 cells. Thus, integrin α(2) expression levels directly correlated with the degree of cell alignment in all examined RPE cell types. Specific integrin subunit α(2)-mediated matrix binding was verified by preincubation with an α(2)-function-blocking antibody, which impaired cell adhesion and alignment to varying degrees in primary and SV40-RPE cells. Since native matrices supported extended and directed primary RPE cell growth, optimizing the matrix production procedure may in the future yield nanostructured collagen matrices serving as transferable cell sheet carriers.

  13. Controlled exosome release from the retinal pigment epithelium in situ.

    Science.gov (United States)

    Locke, Christina J; Congrove, Nicole R; Dismuke, W Michael; Bowen, Trent J; Stamer, W Daniel; McKay, Brian S

    2014-12-01

    Retinal Pigment Epithelial cells (RPE) express both GPR143 and myocilin, which interact in a signal transduction-dependent manner. In heterologous systems, activation of GPR143 with ligand causes transient recruitment of myocilin to internalized receptors, which appears to be the entry point of myocilin to the endocytic pathway. In some but not all cells, myocilin also traffics through the multivesicular body (MVB) and is released on the surface of exosomes in a signal transduction-dependent fashion. Little is known regarding the role of exosomes in RPE, but they likely serve as a mode of communication between the RPE and the outer retina. In this study, we used posterior poles with retina removed from fresh human donor eyes as a model to test the relationship between GPR143, myocilin, and exosomes in an endogenous system. We isolated exosomes released by RPE using differential centrifugation of media conditioned by the RPE for 25 min, and then characterized the exosomes using nanoparticle tracking to determine the number and size of the exosomes. Next, we tested whether ligand stimulation of GPR143 using l-DOPA altered RPE exosome release. Finally, we investigated whether myocilin was present on the exosomes released by RPE and whether l-DOPA stimulation of GPR143 caused recruitment of myocilin to the endocytic pathway, as we have previously observed using cultured cells. Activation of GPR143 halted RPE exosome release, while simultaneously recruiting myocilin to the endocytic compartment. Together, our results indicate that GPR143 and myocilin function in a signal transduction system that can control exosome release from RPE.

  14. Influence of pigment epithelium-derived factor on outcome after striatal cerebral ischemia in the mouse.

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    Marietta Zille

    Full Text Available We here suggest that pigment epithelium-derived factor (PEDF does not have an effect on lesion size, behavioral outcome, cell proliferation, or cell death after striatal ischemia in the mouse. PEDF is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. It influences self-renewal of neural stem cells and proliferation of microglia. We investigated whether intraventricular infusion of PEDF reduces infarct size and cell death, ameliorates behavioral outcome, and influences cell proliferation in the one-hour middle cerebral artery occlusion (MCAO mouse model of focal cerebral ischemia. C57Bl6/N mice were implanted with PEDF or artificial cerebrospinal fluid (control osmotic pumps and subjected to 60-minute MCAO 48 hours after pump implantation. They received daily BrdU injections for 7 days after MCAO in order to investigate cell proliferation. Infarct volumes were determined 24 hours after reperfusion using magnetic resonance imaging. We removed the pumps on day 5 and performed behavioral testing between day 7 and 21. Immunohistochemical staining was performed to determine the effect of PEDF on cell proliferation and cell death. Our model produced an ischemic injury confined solely to striatal damage. We detected no reduction in infarct sizes and cell death in PEDF- vs. CSF-infused MCAO mice. Behavioral outcome and cell proliferation did not differ between the groups. However, we cannot exclude that PEDF might work under different conditions in stroke. Further studies will elucidate the effect of PEDF treatment on cell proliferation and behavioral outcome in moderate to severe ischemic injury in the brain.

  15. [Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes].

    Science.gov (United States)

    Echevarría, L; Villena, O; Nievas, T; Bellido, R

    2015-02-01

    A 58 year-old female was diagnosed with a juxtapapillary combined hamartoma of the retina and retinal pigment epithelium (CHR-RPE) in her left eye 14 years ago. Her visual acuity in that eye was 20/20. Recently, she came to our department with a sudden visual loss and metamorphopsis in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border, and started on antiangiogenic therapy. CHR-RPE, despite being a benign condition, may become complicated with severe visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from these treatment to the complications associated with this pathology. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  16. A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development.

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    Kapil Bharti

    2012-07-01

    Full Text Available The separation of the optic neuroepithelium into future retina and retinal pigment epithelium (RPE is a critical event in early eye development in vertebrates. Here we show in mice that the transcription factor PAX6, well-known for its retina-promoting activity, also plays a crucial role in early pigment epithelium development. This role is seen, however, only in a background genetically sensitized by mutations in the pigment cell transcription factor MITF. In fact, a reduction in Pax6 gene dose exacerbates the RPE-to-retina transdifferentiation seen in embryos homozygous for an Mitf null allele, and it induces such a transdifferentiation in embryos that are either heterozygous for the Mitf null allele or homozygous for an RPE-specific hypomorphic Mitf allele generated by targeted mutation. Conversely, an increase in Pax6 gene dose interferes with transdifferentiation even in homozygous Mitf null embryos. Gene expression analyses show that, together with MITF or its paralog TFEC, PAX6 suppresses the expression of Fgf15 and Dkk3. Explant culture experiments indicate that a combination of FGF and DKK3 promote retina formation by inhibiting canonical WNT signaling and stimulating the expression of retinogenic genes, including Six6 and Vsx2. Our results demonstrate that in conjunction with Mitf/Tfec Pax6 acts as an anti-retinogenic factor, whereas in conjunction with retinogenic genes it acts as a pro-retinogenic factor. The results suggest that careful manipulation of the Pax6 regulatory circuit may facilitate the generation of retinal and pigment epithelium cells from embryonic or induced pluripotent stem cells.

  17. MicroRNA expression profiles of human iPS cells, retinal pigment epithelium derived from iPS, and fetal retinal pigment epithelium.

    Science.gov (United States)

    Greene, Whitney A; Muñiz, Alberto; Plamper, Mark L; Kaini, Ramesh R; Wang, Heuy-Ching

    2014-06-24

    The objective of this report is to describe the protocols for comparing the microRNA (miRNA) profiles of human induced-pluripotent stem (iPS) cells, retinal pigment epithelium (RPE) derived from human iPS cells (iPS-RPE), and fetal RPE. The protocols include collection of RNA for analysis by microarray, and the analysis of microarray data to identify miRNAs that are differentially expressed among three cell types. The methods for culture of iPS cells and fetal RPE are explained. The protocol used for differentiation of RPE from human iPS is also described. The RNA extraction technique we describe was selected to allow maximal recovery of very small RNA for use in a miRNA microarray. Finally, cellular pathway and network analysis of microarray data is explained. These techniques will facilitate the comparison of the miRNA profiles of three different cell types.

  18. Lipofuscin and A2E accumulate with age in the retinal pigment epithelium of Nrl-/- mice.

    Science.gov (United States)

    Boyer, Nicholas P; Tang, Peter H; Higbee, Daniel; Ablonczy, Zsolt; Crouch, Rosalie K; Koutalos, Yiannis

    2012-01-01

    Lipofuscin is a fluorescent material with significant phototoxic potential that accumulates with age in the retinal pigment epithelium (RPE) of the eye. It is thought to be a factor in retinal degeneration diseases. The most extensively characterized lipofuscin component, N-retinylidene-N-retinylethanolamine (A2E), has been proposed to be a byproduct of reactions involving the visual pigment chromophore. To examine the impact of the visual pigment and photoreceptor cell type on lipofuscin accumulation, we analyzed the RPE from Nrl(-/-) mice of various ages for lipofuscin fluorescence and A2E levels. The photoreceptor cells of the Nrl(-/-) retina contain only cone-like pigments, and produce cone-like responses to photostimulation. The cone-like nature of these cells was confirmed by the presence of RPE65. Lipofuscin was measured with fluorescence imaging, whereas A2E was quantified by UV/VIS absorbance spectroscopy coupled to HPLC. The identity of A2E was corroborated with tandem mass spectrometry. Lipofuscin and A2E accumulated with age, albeit to lower levels compared with wild type mice. The emission spectra of RPE lipofuscin granules from Nrl(-/-) mice were similar to those from wild type mice, with λ(max) ca 610 nm. These results demonstrate that cone visual pigments can contribute to the production of lipofuscin and A2E. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  19. Activation of Complement by Pigment Epithelium-Derived Factor in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Vogt, Leonie M.; Talens, Simone; Kwasniewicz, Ewa

    2017-01-01

    neoepitope in C4d, several molecules that were specifically bound to C4d were identified from pooled synovial fluid (SF) from four rheumatoid arthritis (RA) patients. One of these molecules, pigment epithelium-derived factor (PEDF), is a broadly expressed multifunctional member of the serine proteinase...... inhibitor family. Using ELISA, we confirmed the presence of various amounts of complexes between PEDF and C4d in the SF from 30 RA patients, whereas none were detected in SF from control subjects. Correlation analyses suggested that, in arthritis patients, C4d-PEDF complexes found in sera arise from...

  20. Derivation of Neural Progenitors and Retinal Pigment Epithelium from Common Marmoset and Human Pluripotent Stem Cells

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    Laughing Bear Torrez

    2012-01-01

    Full Text Available Embryonic and induced pluripotent stem cells (IPSCs derived from mammalian species are valuable tools for modeling human disease, including retinal degenerative eye diseases that result in visual loss. Restoration of vision has focused on transplantation of neural progenitor cells (NPCs and retinal pigmented epithelium (RPE to the retina. Here we used transgenic common marmoset (Callithrix jacchus and human pluripotent stem cells carrying the enhanced green fluorescent protein (eGFP reporter as a model system for retinal differentiation. Using suspension and subsequent adherent differentiation cultures, we observed spontaneous in vitro differentiation that included NPCs and cells with pigment granules characteristic of differentiated RPE. Retinal cells derived from human and common marmoset pluripotent stem cells provide potentially unlimited cell sources for testing safety and immune compatibility following autologous or allogeneic transplantation using nonhuman primates in early translational applications.

  1. Automated Imaging System for Pigmented Skin Lesion Diagnosis

    Directory of Open Access Journals (Sweden)

    Mariam Ahmed Sheha

    2016-10-01

    Full Text Available Through the study of pigmented skin lesions risk factors, the appearance of malignant melanoma turns the anomalous occurrence of these lesions to annoying sign. The difficulty of differentiation between malignant melanoma and melanocytic naive is the error-bone problem that usually faces the physicians in diagnosis. To think through the hard mission of pigmented skin lesions diagnosis different clinical diagnosis algorithms were proposed such as pattern analysis, ABCD rule of dermoscopy, Menzies method, and 7-points checklist. Computerized monitoring of these algorithms improves the diagnosis of melanoma compared to simple naked-eye of physician during examination. Toward the serious step of melanoma early detection, aiming to reduce melanoma mortality rate, several computerized studies and procedures were proposed. Through this research different approaches with a huge number of features were discussed to point out the best approach or methodology could be followed to accurately diagnose the pigmented skin lesion. This paper proposes automated system for diagnosis of melanoma to provide quantitative and objective evaluation of skin lesion as opposed to visual assessment, which is subjective in nature. Two different data sets were utilized to reduce the effect of qualitative interpretation problem upon accurate diagnosis. Set of clinical images that are acquired from a standard camera while the other set is acquired from a special dermoscopic camera and so named dermoscopic images. System contribution appears in new, complete and different approaches presented for the aim of pigmented skin lesion diagnosis. These approaches result from using large conclusive set of features fed to different classifiers. The three main types of different features extracted from the region of interest are geometric, chromatic, and texture features. Three statistical methods were proposed to select the most significant features that will cause a valuable effect in

  2. [Effect of cryotherapy over the expression of vascular endothelial growth factor and pigment epithelium-derived factor].

    Science.gov (United States)

    Toscano-Garibay, Julia Dolores; Quiroz-Mercado, Hugo; Espitia-Pinzón, Clara; Gil-Carrasco, Félix; Flores-Estrada, José Javier

    2014-01-01

    Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor. Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription. Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21. This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

  3. Epithelium

    Science.gov (United States)

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  4. Automated segmentation of serous pigment epithelium detachment in SD-OCT images

    Science.gov (United States)

    Sun, Zhuli; Shi, Fei; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

    2015-03-01

    Pigment epithelium detachment (PED) is an important clinical manifestation of multiple chorio-retinal disease processes, which can cause the loss of central vision. A 3-D method is proposed to automatically segment serous PED in SD-OCT images. The proposed method consists of five steps: first, a curvature anisotropic diffusion filter is applied to remove speckle noise. Second, the graph search method is applied for abnormal retinal layer segmentation associated with retinal pigment epithelium (RPE) deformation. During this process, Bruch's membrane, which doesn't show in the SD-OCT images, is estimated with the convex hull algorithm. Third, the foreground and background seeds are automatically obtained from retinal layer segmentation result. Fourth, the serous PED is segmented based on the graph cut method. Finally, a post-processing step is applied to remove false positive regions based on mathematical morphology. The proposed method was tested on 20 SD-OCT volumes from 20 patients diagnosed with serous PED. The average true positive volume fraction (TPVF), false positive volume fraction (FPVF), dice similarity coefficient (DSC) and positive predictive value (PPV) are 97.19%, 0.03%, 96.34% and 95.59%, respectively. Linear regression analysis shows a strong correlation (r = 0.975) comparing the segmented PED volumes with the ground truth labeled by an ophthalmology expert. The proposed method can provide clinicians with accurate quantitative information, including shape, size and position of the PED regions, which can assist diagnose and treatment.

  5. Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of the retinal pigment epithelium.

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    Yogita Kanan

    Full Text Available Lack of tyrosine sulfation of ocular proteins results in disorganized photoreceptor structure and drastically reduced visual function, demonstrating the importance of this post-translational modification to vision. To understand the role that tyrosine sulfation plays in the function of ocular proteins, we identified some tyrosine-sulfated proteins in the retinal pigment epithelium using two independent methods, immuno-affinity column purification with an anti-sulfotyrosine specific antibody and computer-based sequence analysis of retinal pigment epithelium secretome by means of the prediction program Sulfinator. Radioactive labeling followed by thin layer electrophoresis revealed that three proteins, vitronectin, opticin, and complement factor H (CFH, were post-translationally modified by tyrosine sulfation. The identification of vitronectin and CFH as tyrosine-sulfated proteins is significant, since both are deposited in drusen in the eyes of patients with age-related macular degeneration (AMD. Furthermore, mutations in CFH have been determined to be a major risk factor in the development of AMD. Future studies that seek to understand the role of CFH in the development of AMD should take into account the role that tyrosine sulfation plays in the interaction of this protein with its partners, and examine whether modulating sulfation provides a potential therapeutic target.

  6. Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

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    Jung-Tung Liu

    2012-01-01

    Full Text Available Pigment epithelium-derived factor (PEDF was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.

  7. Magnetic Nanoparticles as Intraocular Drug Delivery System to Target Retinal Pigmented Epithelium (RPE

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    Martina Giannaccini

    2014-01-01

    Full Text Available One of the most challenging efforts in drug delivery is the targeting of the eye. The eye structure and barriers render this organ poorly permeable to drugs. Quite recently the entrance of nanoscience in ocular drug delivery has improved the penetration and half-life of drugs, especially in the anterior eye chamber, while targeting the posterior chamber is still an open issue. The retina and the retinal pigment epithelium/choroid tissues, located in the posterior eye chamber, are responsible for the majority of blindness both in childhood and adulthood. In the present study, we used magnetic nanoparticles (MNPs as a nanotool for ocular drug delivery that is capable of specific localization in the retinal pigmented epithelium (RPE layer. We demonstrate that, following intraocular injection in Xenopus embryos, MNPs localize specifically in RPE where they are retained for several days. The specificity of the localization did not depend on particle size and surface properties of the MNPs used in this work. Moreover, through similar experiments in zebrafish, we demonstrated that the targeting of RPE by the nanoparticles is not specific for the Xenopus species.

  8. Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

    Science.gov (United States)

    Higdon, Charles W; Mitra, Robi D; Johnson, Stephen L

    2013-01-01

    In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

  9. Gene expression analysis of zebrafish melanocytes, iridophores, and retinal pigmented epithelium reveals indicators of biological function and developmental origin.

    Directory of Open Access Journals (Sweden)

    Charles W Higdon

    Full Text Available In order to facilitate understanding of pigment cell biology, we developed a method to concomitantly purify melanocytes, iridophores, and retinal pigmented epithelium from zebrafish, and analyzed their transcriptomes. Comparing expression data from these cell types and whole embryos allowed us to reveal gene expression co-enrichment in melanocytes and retinal pigmented epithelium, as well as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes and retinal pigmented epithelium, indicating the shared functions of melanin-producing cells. We found 62 genes significantly co-enriched in melanocytes and iridophores, illustrative of their shared developmental origins from the neural crest. This is also the first analysis of the iridophore transcriptome. Gene expression analysis for iridophores revealed extensive enrichment of specific enzymes to coordinate production of their guanine-based reflective pigment. We speculate the coordinated upregulation of specific enzymes from several metabolic pathways recycles the rate-limiting substrate for purine synthesis, phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification procedure and expression analysis described here, along with the accompanying transcriptome-wide expression data, provide the first mRNA sequencing data for multiple purified zebrafish pigment cell types, and will be a useful resource for further studies of pigment cell biology.

  10. Change of morphological and functional characteristics of retinal pigment epithelium cells during cultivation of retinal pigment epithelium-choroid perfusion tissue culture.

    Science.gov (United States)

    Miura, Yoko; Klettner, Alexa; Noelle, Bernhard; Hasselbach, Heike; Roider, Johann

    2010-01-01

    To evaluate the changes of morphological and functional characteristics of the retinal pigment epithelium (RPE)-choroid perfusion culture during cultivation. PorcineRPE-choroid tissue was cultivated in a perfusion tissue culture system. After the indicated times, histology, immunolocalization of collagen IV and von Willebrand factor, RPE cell viability with calcein-AM, TUNEL assay and occludin immunolocalization of RPE cells were examined. The tissue was treated with selective RPE treatment laser after different time periods and the wound healing response was characterized. Vascular endothelial growth factor secretion was measured by enzyme-linked immunosorbent assay. On day 8, prominent morphological degenerative changes of RPE cells were observed in histology. According to the immunohistochemistry for collagen IV, the Bruch's membrane did not display any obvious decomposition until day 8. Von Willebrand factor staining decreased during cultivation, especially at the choriocapillaris. Calcein-AM staining and TUNEL assay displayed the increase of apoptotic changes in only a minority of the cells on day 4, but in many cells on day 8. Occludin delocalization was observed on day 8. Selective RPE treatment laser-produced wounds were completely closed by monolayer RPE when wounded on fresh and 3-day-old cultures, but not when wounded on 6-day-old cultures. Vascular endothelial growth factor secretion was stable between days 2 and 5, but increased after that. Under the stated culture perfusion conditions, porcine RPE-choroid tissue was suitable for experimentation up to 5 days of maintenance. Copyright 2009 S. Karger AG, Basel.

  11. The pineal gland does not control rod outer segment shedding and phagocytosis in the rat retina and pigment epithelium.

    Science.gov (United States)

    Tamai, M; Teirstein, P; Goldman, A; O'Brien, P; Chader, G

    1978-06-01

    Diurnal patterns of retinal outer segment shedding and phagocytosis by the pigment epithelium were examined in pinealectomized, superior-cervical-ganglionectomized, and sham-operated rats. Phagocytosis was quantitatively similar in all groups. Sharp increases in the number of large phagosomes were observed soon after lights were turned on in the tree sets of animals. Pinealectomized animals kept in constant darkness over a 24 hr period also exhibited normal shedding patterns. Our results suggest that the pineal does not exert a major influence on the daily rhythms of shedding and phagocytosis observed in the retina-pigment epithelium unit.

  12. Structure and function of the retinal pigment epithelium, photoreceptors and cornea in the eye of Sardinella aurita (Clupeidae, Teleostei

    Directory of Open Access Journals (Sweden)

    Mostafa Ali Salem

    2016-05-01

    Full Text Available The structure of the pigment epithelium, photoreceptors and the cornea in the eye of a teleost, Sardinella aurita was examined by light and electron microscopy. The retinal pigment epithelium forms a single layer of cells joined laterally by cell junctions. Centrally in the retina these cells are columnar, while more peripherally they become cuboidal in shape. The basal (scleral border of the pigment epithelial cells is not infolded but is relatively smooth. Phagosomes containing lysosome-like bodies are also common features of the retinal pigment epithelium. Numerous melanosomes (pigment granules are abundant throughout the epithelial cells. These melanosomes probably absorb light which has passed through the photoreceptor layer. Four photoreceptor cells were identified; rods, long single cones, short single cones and double cones. The presence of these types suggests a diversity of photoreceptor function. Square mosaic pattern of cones and well-developed choroid gland are also main features of the eye. The inner segment of rods and cones were rich in organelles indicating much synthetic activity. Calycal processes projecting from cone outer segments are also observed. The cornea includes an epithelium with a complex pattern of surface microplicae, a basement membrane, dermal stroma, an iridescent layer, scleral stroma, Descemet’s membrane and endothelium. The autochthonous layer which is seen in some teleosts has not been observed in the cornea of this species. These and other observations were discussed in relation to the photic environment and habits of this fish.

  13. Epiretinal membrane surgery for combined hamartoma of the retina and retinal pigment epithelium: role of multimodal analysis

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    Bruè C

    2013-01-01

    Full Text Available Claudia Bruè, Andrea Saitta, Michele Nicolai, Cesare Mariotti, Alfonso GiovanniniOphthalmology, Department of Neuroscience, Marche Polytechnic University, Ancona, ItalyBackground: The purpose of this study was to evaluate the role of spectral domain optical coherence tomography (SD-OCT, MP-1 microperimetry, and fundus autofluorescence imaging for planning surgical procedures in combined hamartomas of the retina and retinal pigment epithelium (CHR-RPE and following epiretinal membrane removal.Methods: In an interventional retrospective case series, six consecutive subjects with CHR-RPE underwent vitrectomy and epiretinal membrane peeling, with 4 years of follow-up. Each underwent complete ophthalmic examination, including best corrected visual acuity, fundus examination, fundus fluorescein angiography, SD-OCT, MP-1, and fundus autofluorescence at one, 6, 12, and 48 months.Results: Six eyes from six subjects with CHR-RPE were studied (mean age 31 ± 14 years. All patients were phakic and five were male (83.3%. Lesions were unilateral, ie, three macular, two juxtapapillary and macular, and one pericentral. Preoperative best corrected visual acuity was 0.3 ± 0.08 Snellen, with significant improvement to 0.9 ± 0.17 Snellen (P = 0.001 at 4 years of follow-up. Mean retinal sensitivity within the central 20° field improved from 16.6 ± 1.84 dB to 18.8 ± 0.96 dB (P = 0.07. There was also a statistically significant reduction in the visual defect (P = 0.04. SD-OCT demonstrated that the epiretinal membranes were completely removed in all but one patient, with significantly decreased macular edema on follow-up at one, 6, 12, and 48 months (P = 0.001. A positive correlation was shown between preoperative macular sensitivity and postoperative best corrected visual acuity. Fundus autofluorescence demonstrated a block in background autofluorescence at the site of the lesion, and hyperautofluorescsence at the edematous retina overlain by the epiretinal

  14. L-cystein protects the pigment epithelium from acute sodium iodate toxicity.

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    Heike, M; Marmor, M F

    1990-08-01

    Intravenous sodium iodate damages the retinal pigment epithelium, causing immediate loss of the electroretinogram c-wave and eventual pigmentary retinopathy. L-cystein, an agent that enhances the c-wave, has been reported to prevent the late development of pigmentary degeneration. We found in rabbits that L-cystein given 30 min before, or simultaneously with (but not 30 min after) sodium iodate also blocks the loss of the c-wave. This result occurred at doses of L-cystein lower than those needed to produce enhancement of the c-wave, suggesting that these two actions of L-cystein may be independent. The iodate-blocking action of L-cystein may depend on chemical interaction.

  15. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death.

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    Meléndez García, Rodrigo; Arredondo Zamarripa, David; Arnold, Edith; Ruiz-Herrera, Xarubet; Noguez Imm, Ramsés; Baeza Cruz, German; Adán, Norma; Binart, Nadine; Riesgo-Escovar, Juan; Goffin, Vincent; Ordaz, Benito; Peña-Ortega, Fernando; Martínez-Torres, Ataúlfo; Clapp, Carmen; Thebault, Stéphanie

    2016-05-01

    The identification of pathways necessary for retinal pigment epithelium (RPE) function is fundamental to uncover therapies for blindness. Prolactin (PRL) receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19) human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2) expression, which inhibits the TRPM2-mediated intracellular Ca(2+) rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr(-/-)) mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  16. Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death

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    Rodrigo Meléndez García

    2016-05-01

    Full Text Available The identification of pathways necessary for retinal pigment epithelium (RPE function is fundamental to uncover therapies for blindness. Prolactin (PRL receptors are expressed in the retina, but nothing is known about the role of PRL in RPE. Using the adult RPE 19 (ARPE-19 human cell line and mouse RPE, we identified the presence of PRL receptors and demonstrated that PRL is necessary for RPE cell survival via anti-apoptotic and antioxidant actions. PRL promotes the antioxidant capacity of ARPE-19 cells by reducing glutathione. It also blocks the hydrogen peroxide-induced increase in deacetylase sirtuin 2 (SIRT2 expression, which inhibits the TRPM2-mediated intracellular Ca2+ rise associated with reduced survival under oxidant conditions. RPE from PRL receptor-null (prlr−/− mice showed increased levels of oxidative stress, Sirt2 expression and apoptosis, effects that were exacerbated in animals with advancing age. These observations identify PRL as a regulator of RPE homeostasis.

  17. Unraveling the cellular uptake of bioreducible poly(amido amine) — Gene complexes in cells of the retinal pigment epithelium

    NARCIS (Netherlands)

    Vercauteren, D.; Piest, M.; Soraj, M. Al; Jones, A.T.; Engbersen, J.F.J.; Smedt, de S.C.; Braeckmans, K.

    2010-01-01

    In vitro endocytosis of gene complexes composed of a bioreducible polyamidoamine CBA ABOL and plasmid DNA, in cells of the retinal pigment epithelium (RPE) was studied, the latter being an interesting target for ocular gene therapy. We found that cationic CBA ABOL DNA polyplexes attach to cell surfa

  18. Threshold determinations for selective retinal pigment epithelium damage with repetitive pulsed microsecond laser systems in rabbits.

    Science.gov (United States)

    Framme, Carsten; Schuele, Georg; Roider, Johann; Kracht, Dietmar; Birngruber, Reginald; Brinkmann, Ralf

    2002-01-01

    In both clinical and animal studies, it has been shown that repetitive short laser pulses can cause selective retinal pigment epithelium damage (RPE) with sparing of photoreceptors. Our purpose was to determine the ophthalmoscopic and angiographic damage thresholds as a function of pulse durations by using different pulsed laser systems to optimize treatment modalities. Chinchilla-breed rabbits were narcotized and placed in a special holding system. Laser lesions were applied using a commercial laser slit lamp, contact lens, and irradiation with a frequency-doubled Nd:YLF laser (wave-length: 527 nm; repetition rate: 500 Hz; number of pulses: 100; pulse duration: 5 micros, 1.7 micros, 200 ns) and an argon-ion laser (514 nm, 500 Hz, 100 pulses, 5 micros and 200 ms). In all eyes, spots with different energies were placed into the regio macularis with a diameter of 102 microm (tophat profile). After treatment, fundus photography and fluorescein angiography were performed and radiant exposure for ED50 damage determined. Speckle measurements at the fiber tips were performed to determine intensity peaks in the beam profile. Using the Nd:YLF laser system, the ophthalmoscopic ED50 threshold energies were 25.4 microJ (5 micros), 32 microJ (1.7 micros), and 30 microJ (200 ns). The angiographic ED50 thresholds were 13.4 microJ (5 micros), 9.2 microJ (1.7 micros), and 6.7 microJ (200 ns). With the argon laser, the angiographic threshold for 5 micros pulses was 5.5 microJ. The ophthalmoscopic threshold could not be determined because of a lack of power; however, it was > 12 microJ. For 200 ms, the ED50 radiant exposures were 20.4 mW ophthalmoscopically and 19.2 mW angiographically. Speckle factors were found to be 1.225 for the Nd:YLF and 3.180 for the argon laser. Thus, the maximal ED50 -threshold radiant exposures for the Nd:YLF were calculated to be 362 mJ/cM2 (5 micros), 478 mJ/cm2 (1.7 micros), and 438 mJ/cm2 (200 ns) ophthalmoscopically. Angiographically, the thresholds

  19. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia.

    Science.gov (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C

    2015-03-01

    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  20. Proteomic Profiling of Cigarette Smoke Induced Changes in Retinal Pigment Epithelium Cells.

    Science.gov (United States)

    Merl-Pham, Juliane; Gruhn, Fabian; Hauck, Stefanie M

    2016-01-01

    Age-related macular degeneration (AMD) is a medical condition usually affecting older adults and resulting in a loss of vision in the macula, the center of the visual field. The dry form of this disease presents with atrophy of the retinal pigment epithelium, resulting in the detachment of the retina and loss of photoreceptors. Cigarette smoke is one main risk factor for dry AMD and increases the risk of developing the disease by three times. In order to understand the influence of cigarette smoke on retinal pigment epithelial cells, cultured human ARPE-19 cells were treated with cigarette smoke extract for 24 h. Using quantitative mass spectrometry more than 3000 proteins were identified and their respective abundances were compared between cigarette smoke-treated and untreated cells. Altogether 1932 proteins were quantified with at least two unique peptides, with 686 proteins found to be significantly differentially abundant with p > 0.05. Of these proteins the abundance of 64 proteins was at least 2-fold down-regulated after cigarette smoke treatment while 120 proteins were 2-fold up-regulated. The analysis of associated biological processes revealed an alteration of proteins involved in RNA processing and transport as well as extracellular matrix remodelling in response to cigarette smoke treatment.

  1. Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

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    Silène T Wavre-Shapton

    Full Text Available The retinal pigment epithelium (RPE is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1. REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox, Tyr-Cre+. Transmission electron microscopy (TEM was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox, Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

  2. Automated Dermoscopy Image Analysis of Pigmented Skin Lesions

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    Alfonso Baldi

    2010-03-01

    Full Text Available Dermoscopy (dermatoscopy, epiluminescence microscopy is a non-invasive diagnostic technique for the in vivo observation of pigmented skin lesions (PSLs, allowing a better visualization of surface and subsurface structures (from the epidermis to the papillary dermis. This diagnostic tool permits the recognition of morphologic structures not visible by the naked eye, thus opening a new dimension in the analysis of the clinical morphologic features of PSLs. In order to reduce the learning-curve of non-expert clinicians and to mitigate problems inherent in the reliability and reproducibility of the diagnostic criteria used in pattern analysis, several indicative methods based on diagnostic algorithms have been introduced in the last few years. Recently, numerous systems designed to provide computer-aided analysis of digital images obtained by dermoscopy have been reported in the literature. The goal of this article is to review these systems, focusing on the most recent approaches based on content-based image retrieval systems (CBIR.

  3. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    Science.gov (United States)

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Pigment Epithelium-derived Factor in Cataractous Aqueous Humor and Lens Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Tian Liu; Yizhi Liu; Mingxing Wu

    2006-01-01

    Purpose:To study the characteristics of PEDF in cataractous aqueous humor and its expression in human lens epithelium.Methods:The PEDF concentration in the aqueous humor was measured by enzyme linked immunosorbent assay in senile (130cases) and congenital (18cases) cataract patients who underwent cataract phacoemulsification extraction surgery. Anterior lens capsular specimens were obtained from these patients to count lens epithelial cells(LEC) density. The Lens Opacities Classification System Ⅲ was used to classify the senile cataracts as cortical, nuclear, posterior subcapsular and mixed types of opacity, and quantitative analysis of the nuclear opacities was performed by Pentacam Scheimpflug imaging system. Anterior lens capsular specimens from another senile(10cases) and congenital (10cases) cataract were collected for immunofluorescence with polyclonal antibodies specific to human pigment epithelium-derived factor(PEDF).Results:The mean aqueous level of PEDF was(178. 9±87. 5)ng/ml, and there was negative linear correlation of PEDF level and age (r=0. 811, P < 0. 001) . In senile cases, the aqueous PEDF concentration decreased with increasing nuclear opacities(r=0. 447, P < 0.01 ), and the mean PEDF level in nuclear cataract was significantly lower than that in posterior subcapsular opacity (P < 0.01 ) . PEDF immunostaining was detected in LEC of all capsular specimens.Conclusion :The PEDF level in human aqueous humor is related to age, types of cataracts and lens opacity. PEDF also express in human LEC. The study results suggest PEDF may regulate and/or protect LEC by paracrine and autocrine, and lack of PEDF may play a role in cataractogenesis.

  5. Anatomical and visual outcomes of ranibizumab injections in retinal pigment epithelium tears

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    Muhammet Kazım Erol

    2015-06-01

    Full Text Available ABSTRACT Purpose: To report the anatomical and visual results in patients diagnosed as having retinal pigment epithelium (RPE tears after receiving ranibizumab injections. Methods: Eyes diagnosed as having RPE tears with a minimum 6-month follow-up were retrospectively evaluated. Each eye was treated with at least three doses of ranibizumab at monthly intervals. Best-corrected visual acuity (BCVA, anterior segment findings, intraocular pressure, and fundus examination results were evaluated during control visits. Color fundus photography, fundus fluorescein angiographies, fundus autofluorescence, and spectral domain optical coherence tomography (SD-OCT images were obtained. The height of pigment epithelial detachment (PED was measured by SD-OCT. Results: Twelve eyes with RPE tears were studied. Nine eyes (75% developed RPE tears during ranibizumab injections for choroidal neovascularization (eight eyes with vascularized PED and one eye with choroidal osteoma, and tears occurred in three eyes before any injections. The median number of ranibizumab injections after diagnosis of RPE tears was 3 (min 2, max 5. In the most recent follow-up visit, there was no statistically significant correlation between the grade of RPE and logMAR of BCVA (p>0.05, r=0.112. Eight of twelve eyes had PED, and seven of these had irregular PED contours before injection therapy. The mean PED height was 447 ± 122 µm. Conclusions: In this series, RPE tears developed mostly after intravitreal anti-VEGF injections for vascularized PED. Increased vertical height and irregular contours of the PEDs can be risk factors for the formation of RPE tears. The continuation of anti-VEGF therapy after tear formation is beneficial for vision improvement in eyes with RPE tears.

  6. BMP-induced reprogramming of the neural retina into retinal pigment epithelium requires Wnt signalling

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    Jörg Steinfeld

    2017-07-01

    Full Text Available In vertebrates, the retinal pigment epithelium (RPE and photoreceptors of the neural retina (NR comprise a functional unit required for vision. During vertebrate eye development, a conversion of the RPE into NR can be induced by growth factors in vivo at optic cup stages, but the reverse process, the conversion of NR tissue into RPE, has not been reported. Here, we show that bone morphogenetic protein (BMP signalling can reprogram the NR into RPE at optic cup stages in chick. Shortly after BMP application, expression of Microphthalmia-associated transcription factor (Mitf is induced in the NR and selective cell death on the basal side of the NR induces an RPE-like morphology. The newly induced RPE differentiates and expresses Melanosomalmatrix protein 115 (Mmp115 and RPE65. BMP-induced Wnt2b expression is observed in regions of the NR that become pigmented. Loss of function studies show that conversion of the NR into RPE requires both BMP and Wnt signalling. Simultaneous to the appearance of ectopic RPE tissue, BMP application reprogrammed the proximal RPE into multi-layered retinal tissue. The newly induced NR expresses visual segment homeobox-containing gene (Vsx2, and the ganglion and photoreceptor cell markers Brn3α and Visinin are detected. Our results show that high BMP concentrations are required to induce the conversion of NR into RPE, while low BMP concentrations can still induce transdifferentiation of the RPE into NR. This knowledge may contribute to the development of efficient standardized protocols for RPE and NR generation for cell replacement therapies.

  7. The Retinal Pigment Epithelium: a Convenient Source of New Photoreceptor cells?

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    Shu-Zhen Wang

    2014-01-01

    Full Text Available Recent success in restoring visual function through photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to generate or regenerate photoreceptor cells for the ultimate goal of using cell replacement therapy for blindness caused by photoreceptor degeneration. Current research on deriving new photoreceptors for replacement, as regenerative medicine in general, focuses on the use of embryonic stem cells and induced pluripotent stem (iPS cells to generate transplantable cells. Nonetheless, naturally occurring regeneration, such as wound healing, involves awakening cells at or near a wound site to produce new cells needed to heal the wound. Here we discuss the possibility of tweaking an ocular tissue, the retinal pigment epithelium (RPE, to produce photoreceptor cells in situ in the eye. Unlike the neural retina, the RPE in adult mammals maintains cell proliferation capability. Furthermore, progeny cells from RPE proliferation may differentiate into cells other than RPE. The combination of proliferation and plasticity opens a question of whether they could be channeled by a regulatory gene with pro-photoreceptor activity towards photoreceptor production. Studies using embryonic chick and transgenic mouse showed that indeed photoreceptor-like cells were produced in culture and in vivo in the eye using genedirected reprogramming of RPE cells, supporting the feasibility of using the RPE as a convenient source of new photoreceptor cells for in situ retinal repair without involving cell transplantation.

  8. Applying photoacoustics to quantification of melanin concentration in retinal pigment epithelium (Conference Presentation)

    Science.gov (United States)

    Shu, Xiao; Zhang, Hao F.; Liu, Wenzhong

    2016-03-01

    The melanin in the retinal pigment epithelium (RPE) protects retina and other ocular tissues by photo-screening and acting as antioxidant and free radical scavenger. It helps maintain normal visual functions since human eye is subjected to lifelong high oxygen stress and photon exposure. Loss of the RPE melanin weakens the protection mechanism and jeopardizes ocular health. Local decrease in the RPE melanin concentration is believed to be both a cause and a sign of early-stage age-related macular degeneration (AMD), the leading blinding disease in developed world. Current technology cannot quantitatively measure the RPE melanin concentration which might be a promising marker in early AMD screening. Photoacoustic ophthalmoscopy (PAOM), as an emerging optical absorption-based imaging technology, can potentially be applied to measure the RPE melanin concentration if the dependence of the detectable photoacoustic (PA) signal amplitudes on the RPE melanin concentrations is verified. In this study, we tested the feasibility of using PA signal ratio from RPE melanin and the nearby retinal blood vessels as an indicator of the RPE melanin variation. A novel whole eye optical model was designed and Monte Carlo modeling of light (MCML) was employed. We examined the influences on quantification from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness. The results show that the scheme is robust to individual histological and illumination variations. This study suggests that PAOM is capable of quantitatively measuring the RPE melanin concentration in vivo.

  9. A strategy to ensure safety of stem cell-derived retinal pigment epithelium cells.

    Science.gov (United States)

    Choudhary, Parul; Whiting, Paul John

    2016-09-02

    Cell replacement and regenerative therapy using embryonic stem cell-derived material holds promise for the treatment of several pathologies. However, the safety of this approach is of prime importance given the teratogenic potential of residual stem cells, if present in the differentiated cell product. Using the example of embryonic stem cell-derived retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration, we present a novel strategy for ensuring the absence of stem cells in the RPE population. Based on an unbiased screening approach, we identify and validate the expression of CD59, a cell surface marker expressed on RPE but absent on stem cells. We further demonstrate that flow sorting on the basis of CD59 expression can effectively purify RPE and deplete stem cells, resulting in a population free from stem cell impurity. This purification helps to ensure removal of stem cells and hence increases the safety of cells that may be used for clinical transplantation. This strategy can potentially be applied to other pluripotent stem cell-derived material and help mitigate concerns of using such cells for therapy.

  10. Effects of white light-emitting diode (LED) exposure on retinal pigment epithelium in vivo.

    Science.gov (United States)

    Jaadane, Imene; Villalpando Rodriguez, Gloria Elisa; Boulenguez, Pierre; Chahory, Sabine; Carré, Samuel; Savoldelli, Michèle; Jonet, Laurent; Behar-Cohen, Francine; Martinsons, Christophe; Torriglia, Alicia

    2017-06-29

    Ageing and alteration of the functions of the retinal pigment epithelium (RPE) are at the origin of lost of vision seen in age-related macular degeneration (AMD). The RPE is known to be vulnerable to high-energy blue light. The white light-emitting diodes (LED) commercially available have relatively high content of blue light, a feature that suggest that they could be deleterious for this retinal cell layer. The aim of our study was to investigate the effects of "white LED" exposure on RPE. For this, commercially available white LEDs were used for exposure experiments on Wistar rats. Immunohistochemical stain on RPE flat mount, transmission electron microscopy and Western blot were used to exam the RPE. LED-induced RPE damage was evaluated by studying oxidative stress, stress response pathways and cell death pathways as well as the integrity of the outer blood-retinal barrier (BRB). We show that white LED light caused structural alterations leading to the disruption of the outer blood-retinal barrier. We observed an increase in oxidized molecules, disturbance of basal autophagy and cell death by necrosis. We conclude that white LEDs induced strong damages in rat RPE characterized by the breakdown of the BRB and the induction of necrotic cell death. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Aliskiren inhibits the renin-angiotensin system in retinal pigment epithelium cells.

    Science.gov (United States)

    Simão, Sónia; Santos, Daniela F; Silva, Gabriela A

    2016-09-20

    Observations of increased angiotensin II levels and activation of the (pro)renin receptor in retinopathies support the role of ocular renin-angiotensin system (RAS) in the development of retinal diseases. While targeting RAS presents significant therapeutic potential, current RAS-based therapies are ineffective halting the progression of these diseases. A new class of drugs, the direct renin inhibitors such as aliskiren, is a potential therapeutic alternative. However, it is unclear how aliskiren acts in the retina, in particular in the retinal pigment epithelium (RPE), the structure responsible for the maintenance of retinal homeostasis whose role is deeply compromised in retinal diseases. We firstly analyzed the expression and activity of the main RAS components in RPE cells. Time- and concentration-dependent treatments with aliskiren were performed to modulate different pathways of the RAS in RPE cells. Our data demonstrate that RPE cells express the main RAS constituents. Exposure of RPE cells to aliskiren inhibited the activity of renin and consequently decreased the levels of angiotensin II. Additionally, aliskiren reduced the translocation of the (pro)renin receptor to the cellular membrane of RPE cells preventing the activation of ERK1/2. Our findings of the RPE well-defined RAS, together with the demonstration that aliskiren effectively blocks this system at different steps of the cascade, suggest that aliskiren might be an alternative and successful drug in preventing the deleterious effects derived from the overactivation of the RAS, known to contribute to the pathogenesis of different retinal diseases.

  12. Bacterial cellulose as a support for the growth of retinal pigment epithelium.

    Science.gov (United States)

    Gonçalves, Sara; Padrão, Jorge; Rodrigues, Inês Patrício; Silva, João Pedro; Sencadas, Vítor; Lanceros-Mendez, Senentxu; Girão, Henrique; Dourado, Fernando; Rodrigues, Lígia R

    2015-04-13

    The feasibility of bacterial cellulose (BC) as a novel substrate for retinal pigment epithelium (RPE) culture was evaluated. Thin (41.6 ± 2.2 μm of average thickness) and heat-dried BC substrates were surface-modified via acetylation and polysaccharide adsorption, using chitosan and carboxymethyl cellulose. All substrates were characterized according to their surface chemistry, wettability, energy, topography, and also regarding their permeability, dimensional stability, mechanical properties, and endotoxin content. Then, their ability to promote RPE cell adhesion and proliferation in vitro was assessed. All surface-modified BC substrates presented similar permeation coefficients with solutes of up to 300 kDa. Acetylation of BC decreased it's swelling and the amount of endotoxins. Surface modification of BC greatly enhanced the adhesion and proliferation of RPE cells. All samples showed similar stress-strain behavior; BC and acetylated BC showed the highest elastic modulus, but the latter exhibited a slightly smaller tensile strength and elongation at break as compared to pristine BC. Although similar proliferation rates were observed among the modified substrates, the acetylated ones showed higher initial cell adhesion. This difference may be mainly due to the moderately hydrophilic surface obtained after acetylation.

  13. Acetylated bacterial cellulose coated with urinary bladder matrix as a substrate for retinal pigment epithelium.

    Science.gov (United States)

    Gonçalves, Sara; Rodrigues, Inês Patrício; Padrão, Jorge; Silva, João Pedro; Sencadas, Vitor; Lanceros-Mendez, Senentxu; Girão, Henrique; Gama, Francisco M; Dourado, Fernando; Rodrigues, Lígia R

    2016-03-01

    This work evaluated the effect of acetylated bacterial cellulose (ABC) substrates coated with urinary bladder matrix (UBM) on the behavior of retinal pigment epithelium (RPE), as assessed by cell adhesion, proliferation and development of cell polarity exhibiting transepithelial resistance and polygonal shaped-cells with microvilli. Acetylation of bacterial cellulose (BC) generated a moderate hydrophobic surface (around 65°) while the adsorption of UBM onto these acetylated substrates did not affect significantly the surface hydrophobicity. The ABS substrates coated with UBM enabled the development of a cell phenotype closer to that of native RPE cells. These cells were able to express proteins essential for their cytoskeletal organization and metabolic function (ZO-1 and RPE65), while showing a polygonal shaped morphology with microvilli and a monolayer configuration. The coated ABC substrates were also characterized, exhibiting low swelling effect (between 1.5-2.0 swelling/mm(3)), high mechanical strength (2048MPa) and non-pyrogenicity (2.12EU/L). Therefore, the ABC substrates coated with UBM exhibit interesting features as potential cell carriers in RPE transplantation that ought to be further explored.

  14. Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells

    Science.gov (United States)

    Qi, Lei; Lv, Xiujuan; Zhang, Tongwei; Jia, Peina; Yan, Ruiying; Li, Shuli; Zou, Ruitao; Xue, Yuhua; Dai, Liming

    2016-06-01

    A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

  15. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium.

    Science.gov (United States)

    Nociari, Marcelo M; Lehmann, Guillermo L; Perez Bay, Andres E; Radu, Roxana A; Jiang, Zhichun; Goicochea, Shelby; Schreiner, Ryan; Warren, J David; Shan, Jufang; Adam de Beaumais, Ségolène; Ménand, Mickaël; Sollogoub, Matthieu; Maxfield, Frederick R; Rodriguez-Boulan, Enrique

    2014-04-08

    Accumulation of lipofuscin bisretinoids (LBs) in the retinal pigment epithelium (RPE) is the alleged cause of retinal degeneration in genetic blinding diseases (e.g., Stargardt) and a possible etiological agent for age-related macular degeneration. Currently, there are no approved treatments for these diseases; hence, agents that efficiently remove LBs from RPE would be valuable therapeutic candidates. Here, we show that beta cyclodextrins (β-CDs) bind LBs and protect them against oxidation. Computer modeling and biochemical data are consistent with the encapsulation of the retinoid arms of LBs within the hydrophobic cavity of β-CD. Importantly, β-CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively. Furthermore, intravitreal administration of β-CDs reduced significantly the content of bisretinoids in the RPE of DKO animals. Thus, our results demonstrate the effectiveness of β-CDs to complex and remove LB deposits from RPE cells and provide crucial data to develop novel prophylactic approaches for retinal disorders elicited by LBs.

  16. Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs).

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    Demestre, Maria; Terzi, Menderes Yusuf; Mautner, Victor; Vajkoczy, Peter; Kurtz, Andreas; Piña, Ana Luisa

    2013-12-01

    Neurofibromatosis type 1 (NF1) is an inherited genetic disease affecting 1 in 3,500 individuals. A prominent feature of NF1 is the formation of benign tumours of the peripheral nerve sheath (neurofibromas). However, these can become malignant and form highly metastatic malignant peripheral nerve sheath tumours (MPNST), which are usually fatal despite aggressive surgery, chemotherapy, and radiotherapy. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis in several kinds of tumours. The present study was designed to determine the in vitro and in vivo effects of PEDF on MPNST angiogenesis and tumour growth. PEDF inhibited proliferation and augmented apoptosis in S462 MPNST cells after 48 h of treatment in culture. In xenografts of S462 MPNST cells in athymic nude mice, PEDF suppressed MPNST tumour burden, due mainly to inhibition of angiogenesis. These results demonstrate for the first time inhibitory effects of PEDF on the growth of human MPNST via induction of anti-angiogenesis and apoptosis. Our results suggest that PEDF could be a novel approach for future therapeutic purposes against MPNST.

  17. Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever.

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    Veloso, Carlos Eduardo; Schmidt-Erfurth, Ursula; Nehemy, Márcio B

    2015-01-01

    To report the first case of choroidal neovascularization (CNV) secondary to dengue fever. A 54-year-old female was referred to our department with blurred vision and metamorphopsia in her left eye. Two weeks earlier, she had presented all of the classic symptoms of dengue fever including a positive serology. Her best-corrected visual acuity (BCVA) was 20/150 in the left eye. She underwent a fundus examination, fluorescein angiography (FA) and spectral domain optical coherence tomography. All findings were consistent with CNV secondary to dengue fever. FA revealed a classic CNV associated with focal retinal pigment epithelium (RPE) destruction and detachment. Three consecutive monthly injections of intravitreal ranibizumab resulted in functional and anatomical improvement for as long as 6 months with a BCVA of 20/25. However, CNV recurred 2 years later, again with an improvement after ranibizumab therapy, but with persistence of a fibrovascular RPE detachment, highlighting the pathomechanism of a classic CNV formation. Maculopathy in dengue fever may be followed by CNV as a result of the immunologic alteration of the RPE. Physicians should be aware of this manifestation to be able to initiate adequate treatment with excellent functional and anatomical results.

  18. Light-Induced Phosphorylation of Crystallins in the Retinal Pigment Epithelium

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    Lee, Hyunju; Chung, Hyewon; Lee, Sung Haeng; Jahng, Wan Jin

    2017-01-01

    Protein phosphorylations have essential regulatory roles in visual signaling. Previously, we found that phosphorylation of several proteins in the retina and the retinal pigment epithelium (RPE) is involved in anti-apoptotic signaling under oxidative stress conditions, including light exposure. In this study, we used a phosphoprotein enrichment strategy to evaluate the light-induced phosphoproteome of primary bovine RPE cells. Phosphoprotein-enriched extracts from bovine RPE cells exposed to light or dark conditions for 1 hour were separated by 2D SDS-PAGE. Serine and tyrosine phosphorylation were visualized by 2D phospho western blotting and specific phosphorylation sites were analyzed by tandem mass spectrometry. Light induced a marked increase in tyrosine phosphorylation of beta crystallin A3 and A4. The most abundant light-induced up-regulated phosphoproteins were crystallins of 15–25-kDa, including beta crystallin S and zeta crystallin. Phosphorylation of beta crystallin suggests an anti-apoptotic chaperone function in the RPE. Other chaperones, cytoskeletal proteins, and proteins involved in energy balance were expressed at higher levels in the dark. A detailed analysis of RPE phosphoproteins provides a molecular basis for understanding light-induced signal transduction and anti-apoptosis mechanisms. Our data indicates that phosphorylation of crystallins likely represents an important mechanism for RPE shielding from physiological and pathophysiological light-induced oxidative injury. PMID:21094180

  19. Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)

    Science.gov (United States)

    Fritz, Andreas; Ptaszynski, Lars; Stoehr, Hardo; Brinkmann, Ralf

    2007-07-01

    Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.

  20. Monte Carlo investigation on quantifying the retinal pigment epithelium melanin concentration by photoacoustic ophthalmoscopy.

    Science.gov (United States)

    Shu, Xiao; Liu, Wenzhong; Zhang, Hao F

    2015-10-01

    The retinal pigment epithelium (RPE) melanin plays an important role in maintaining normal visual functions. A decrease in the RPE melanin concentration with aging is believed to be associated with several blinding diseases, including age-related macular degeneration. Quantifying the RPE melanin noninvasively is therefore important in evaluating the retinal health and aging conditions. Photoacoustic ophthalmoscopy (PAOM), as an optical absorption-based imaging technology, can potentially be applied to measure variations in the RPE melanin if the relationship between the detected photoacoustic (PA) signal amplitudes and the RPE melanin concentrations can be established. In this work, we tested the feasibility of using PA signals from retinal blood vessels as references to measure RPE melanin variation using Monte Carlo (MC) simulation. The influences from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness were examined. We proposed a calibration scheme by relating detected PA signals to the RPE melanin concentrations, and we found that the scheme is robust to these tested parameters. This study suggests that PAOM has the capability of quantitatively measuring the RPE melanin in vivo.

  1. Regulation of Autophagy by High Glucose in Human Retinal Pigment Epithelium

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    Jin Yao

    2014-01-01

    Full Text Available Background: Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Retinal pigment epithelium (RPE works as the outer blood retina barrier and is vulnerable to energy stress-induced injury. However, the effect of high glucose treatment on autophagy is still unclear in RPE. Methods: Transmission electron microscopy was used to detect the generation of autophagosome. Small interfering RNA (siRNA and MTT was used to determine the effect of autophagy on cell viability. Western blots and immunohistochemistry were used to detect the expression pattern of autophagic markers, including LC3 and p62. Results: High glucose treatment results in a significant increase in the generation of autophagosome and altered expression of LC3 and p62. High glucose-induced autophagy is independent of mTOR signaling, but is mainly regulated via ROS-mediated ER stress signaling. Conclusion: In the scenario of high glucose-induced oxidative stress, autophagy may be required for the removal of damaged proteins, and provide a default mechanism to prevent high glucose-induced injury in RPE.

  2. Defining the proteome of human iris, ciliary body, retinal pigment epithelium, and choroid.

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    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 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.

  3. The Retinome – Defining a reference transcriptome of the adult mammalian retina/retinal pigment epithelium

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    Goetz Thomas

    2004-07-01

    Full Text Available Abstract Background The mammalian retina is a valuable model system to study neuronal biology in health and disease. To obtain insight into intrinsic processes of the retina, great efforts are directed towards the identification and characterization of transcripts with functional relevance to this tissue. Results With the goal to assemble a first genome-wide reference transcriptome of the adult mammalian retina, referred to as the retinome, we have extracted 13,037 non-redundant annotated genes from nearly 500,000 published datasets on redundant retina/retinal pigment epithelium (RPE transcripts. The data were generated from 27 independent studies employing a wide range of molecular and biocomputational approaches. Comparison to known retina-/RPE-specific pathways and established retinal gene networks suggest that the reference retinome may represent up to 90% of the retinal transcripts. We show that the distribution of retinal genes along the chromosomes is not random but exhibits a higher order organization closely following the previously observed clustering of genes with increased expression. Conclusion The genome wide retinome map offers a rational basis for selecting suggestive candidate genes for hereditary as well as complex retinal diseases facilitating elaborate studies into normal and pathological pathways. To make this unique resource freely available we have built a database providing a query interface to the reference retinome 1.

  4. Immunolocalization of lactoferrin in surgically resected pigmented skin lesions

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    G Tuccari

    2009-06-01

    Full Text Available Lactoferrin (Lf expression was determined immunohistochemically in 57 formalin-fixed paraffin-embedded bioptic samples obtained from an equal number of patients treated by surgery to remove pigmented skin lesions (nevi = 23; melanoma = 12; vulgaris and seborrhoeic warts = 12; basal cell carcinoma = 10; in addition, 10 specimens of normal skin were studied as control. On 3 ?m thick sections, depigmentation and antigen retrieval procedures were performed. The Lf immunoreactivity was revealed by a rabbit anti-human Lf. Quantification of Lf immunoreactivity was performed using an intensity-distribution (ID score. Melanocytic cells, regardless of their benign or malignant nature, were consistently stained, with no significant differences in the Lf IDscore between melanomas or nevi. A different intensity of Lf immunoreactivity was encountered in superficial portions of warts, exclusively inside squamous epithelial cells arranged in sheets or whorls of keratin. On the contrary, basal cell carcinomas were always unstained, while a slight Lf positivity was found in focal keratinized areas present in two tumours showing baso-squamous differentiation. The Lf immunoreactivity was localized in the cytoplasm and only occasionally in the nucleus. The biological meaning of Lf in these cases of human skin specimens remains unexplained, although it cannot be ruled out that Lf might be involved in the defense system against tumours, or alternatively, may be used by cells requiring iron availability for their turnover. Moreover, the immunohistochemical expression of Lf in melanocytic lesions might be also related to a Lf-melanin interaction. Finally, the involvement of Lf in skin squamous non-neoplastic elements could be related to its role as one of the molecules modulating an unspecific inflammatory or anti-oxidant response.

  5. ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell-Derived Retinal Pigmented Epithelium.

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    Croze, Roxanne H; Thi, William J; Clegg, Dennis O

    2016-11-01

    Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell-derived RPE (hESC-RPE) attachment, proliferation, and wound closure. H9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined. Pharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition. ROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing. Modulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies.

  6. ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell–Derived Retinal Pigmented Epithelium

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    Croze, Roxanne H.; Thi, William J.; Clegg, Dennis O.

    2016-01-01

    Purpose Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell–derived RPE (hESC-RPE) attachment, proliferation, and wound closure. Methods H9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined. Results Pharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition. Conclusions ROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing. Translational Relevance Modulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies. PMID:27917311

  7. Pigment Epithelium-Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia.

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    Goldberg, Keren; Bar-Joseph, Hadas; Grossman, Hadas; Hasky, Noa; Uri-Belapolsky, Shiri; Stemmer, Salomon M; Chuderland, Dana; Shalgi, Ruth; Ben-Aharon, Irit

    2015-12-01

    Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor-positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro- and anti-angiogenic factors. VEGF is a pro-angiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-α and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies.

  8. Pigment Epithelium Derived Factor Peptide Protects Murine Hepatocytes from Carbon Tetrachloride-Induced Injury.

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    Shou-Chuan Shih

    Full Text Available Fibrogenesis is induced by repeated injury to the liver and reactive regeneration and leads eventually to liver cirrhosis. Pigment epithelium derived factor (PEDF has been shown to prevent liver fibrosis induced by carbon tetrachloride (CCl4. A 44 amino acid domain of PEDF (44-mer was found to have a protective effect against various insults to several cell types. In this study, we investigated the capability of synthetic 44-mer to protect against liver injury in mice and in primary cultured hepatocytes. Acute liver injury, induced by CCl4, was evident from histological changes, such as cell necrosis, inflammation and apoptosis, and a concomitant reduction of glutathione (GSH and GSH redox enzyme activities in the liver. Intraperitoneal injection of the 44-mer into CCl4-treated mice abolished the induction of AST and ALT and markedly reduced histological signs of liver injury. The 44-mer treatment can reduce hepatic oxidative stress as evident from lower levels of lipid hydroperoxide, and higher levels of GSH. CCl4 caused a reduction of Bcl-xL, PEDF and PPARγ, which was markedly restored by the 44-mer treatment. Consequently, the 44-mer suppressed liver fibrosis induced by repeated CCl4 injury. Furthermore, our observations in primary culture of rat hepatocytes showed that PEDF and the 44-mer protected primary rat hepatocytes against apoptosis induced by serum deprivation and TGF-β1. PEDF/44-mer induced cell protective STAT3 phosphorylation. Pharmacological STAT3 inhibition prevented the antiapoptotic action of PEDF/44-mer. Among several PEDF receptor candidates that may be responsible for hepatocyte protection, we demonstrated that PNPLA2 was essential for PEDF/44-mer-mediated STAT3 phosphorylation and antiapoptotic activity by using siRNA to selectively knockdown PNPLA2. In conclusion, the PEDF 44-mer protects hepatocytes from single and repeated CCl4 injury. This protective effect may stem from strengthening the counter oxidative stress

  9. Imaging human retinal pigment epithelium cells using adaptive optics optical coherence tomography

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    Liu, Zhuolin; Kocaoglu, Omer P.; Turner, Timothy L.; Miller, Donald T.

    2016-03-01

    Retinal pigment epithelium (RPE) cells are vital to health of the outer retina, but are often compromised in ageing and major ocular diseases that lead to blindness. Early manifestation of RPE disruption occurs at the cellular level, and while biomarkers at this scale hold considerable promise, RPE cells have proven extremely challenging to image in the living human eye. We present a novel method based on optical coherence tomography (OCT) equipped with adaptive optics (AO) that overcomes the associated technical obstacles. The method takes advantage of the 3D resolution of AO-OCT, but more critically sub-cellular segmentation and registration that permit organelle motility to be used as a novel contrast mechanism. With this method, we successfully visualized RPE cells and characterized their 3D reflectance profile in every subject and retinal location (3° and 7° temporal to the fovea) imaged to date. We have quantified RPE packing geometry in terms of cell density, cone-to-RPE ratio, and number of nearest neighbors using Voronoi and power spectra analyses. RPE cell density (cells/mm2) showed no significant difference between 3° (4,892+/-691) and 7° (4,780+/-354). In contrast, cone-to- RPE ratio was significantly higher at 3° (3.88+/-0.52:1) than 7° (2.31+/- 0.23:1). Voronoi analysis also showed most RPE cells have six nearest neighbors, which was significantly larger than the next two most prevalent associations: five and seven. Averaged across the five subjects, prevalence of cells with six neighbors was 51.4+/-3.58% at 3°, and 54.58+/-3.01% at 7°. These results are consistent with histology and in vivo studies using other imaging modalities.

  10. Deletion of autophagy inducer RB1CC1 results in degeneration of the retinal pigment epithelium.

    Science.gov (United States)

    Yao, Jingyu; Jia, Lin; Khan, Naheed; Lin, Chengmao; Mitter, Sayak K; Boulton, Michael E; Dunaief, Joshua L; Klionsky, Daniel J; Guan, Jun-Lin; Thompson, Debra A; Zacks, David N

    2015-01-01

    Autophagy regulates cellular homeostasis and response to environmental stress. Within the retinal pigment epithelium (RPE) of the eye, the level of autophagy can change with both age and disease. The purpose of this study is to determine the relationship between reduced autophagy and age-related degeneration of the RPE. The gene encoding RB1CC1/FIP200 (RB1-inducible coiled-coil 1), a protein essential for induction of autophagy, was selectively knocked out in the RPE by crossing Best1-Cre mice with mice in which the Rb1cc1 gene was flanked with Lox-P sites (Rb1cc1(flox/flox)). Ex vivo and in vivo analyses, including western blot, immunohistochemistry, transmission electron microscopy, fundus photography, optical coherence tomography, fluorescein angiography, and electroretinography were performed to assess the structure and function of the retina as a function of age. Deletion of Rb1cc1 resulted in multiple autophagy defects within the RPE including decreased conversion of LC3-I to LC3-II, accumulation of autophagy-targeted precursors, and increased numbers of mitochondria. Age-dependent degeneration of the RPE occurred, with formation of atrophic patches, subretinal migration of activated microglial cells, subRPE deposition of inflammatory and oxidatively damaged proteins, subretinal drusenoid deposits, and occasional foci of choroidal neovascularization. There was secondary loss of photoreceptors overlying the degenerated RPE and reduction in the electroretinogram. These observations are consistent with a critical role of autophagy in the maintenance of normal homeostasis in the aging RPE, and indicate that disruption of autophagy leads to retinal phenotypes associated with age-related degeneration.

  11. Recognition of mannose 6-phosphate ligands by dystrophic rat retinal pigment epithelium

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    Tarnowski, B.; Shepherd, V.; McLaughlin, B.

    1986-05-01

    Retinal pigment epithelium (RPE) phagocytize discarded rod outer segments (ROS) during normal eye function. In the dystrophic rat, an animal model for retinitis pigmentosa in humans, ROS phagocytosis is defective. Dystrophic RPE can phagocytize particles other than ROS, suggesting that the defect may be in the RPE phagocytic recognition. They are currently investigating the recognition markers on RPE in dystrophic rats. In studies using ligand-coated latex beads, no uptake of mannose-coated beads was found in dystrophic rat RPE. They found that dystrophic RPE could specifically phagocytize phosphomannan-coated beads. Studies were begun to examine the presence and function of a phosphomannan receptor (PMR) on dystrophic RPE. ..cap alpha..-Mannosidase, isolated from D. discoideum has been shown to be an efficient ligand for the PMR in fibroblasts and macrophages. It is also recognized by the macrophage mannose receptor. Dystrophic rat RPE and retina explants were placed in culture dishes (5-7/well). /sup 125/I-Labelled ..cap alpha..-mannosidase was added to each well in the presence or absence of 10 mM mannose 6-phosphate (M6P) or yeast mannan (lmg/ml). Explants were incubated at 37/sup 0/ for 2 hr., washed and bound /sup 125/I-mannosidase quantitated. Approximately 2-3% of total counts added were bound to the RPE via a M6P-inhibitable recognition process. The binding to RPE was not blocked by mannan. No mannan or M6P-specific binding was found in retina explants. These results support the findings of specific uptake of phosphomannan-coated beads and demonstrate the presence of a specific PMR on dystrophic RPE phagocytic membranes.

  12. Pigment epithelium-derived factor as a multifunctional regulator of wound healing

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    Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

    2015-01-01

    During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

  13. Pigment epithelium-derived factor as a multifunctional regulator of wound healing.

    Science.gov (United States)

    Wietecha, Mateusz S; Król, Mateusz J; Michalczyk, Elizabeth R; Chen, Lin; Gettins, Peter G; DiPietro, Luisa A

    2015-09-01

    During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. Copyright © 2015 the American Physiological Society.

  14. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress

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    Wang, Kaijun [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Jiang, Yiqian [The First People Hospital of Xiaoshan, Hangzhou (China); Wang, Wei; Ma, Jian [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Chen, Min, E-mail: eyedrchenminzj@163.com [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China)

    2015-12-25

    Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H{sub 2}O{sub 2}) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H{sub 2}O{sub 2}-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H{sub 2}O{sub 2} were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H{sub 2}O{sub 2}. Reversely, escin was more potent against H{sub 2}O{sub 2} damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H{sub 2}O{sub 2} was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling.

  15. Molecular phylogeny of the antiangiogenic and neurotrophic serpin, pigment epithelium derived factor in vertebrates

    Science.gov (United States)

    Xu, Xuming; Zhang, Samuel Shao-Min; Barnstable, Colin J; Tombran-Tink, Joyce

    2006-01-01

    Background Pigment epithelium derived factor (PEDF), a member of the serpin family, regulates cell proliferation, promotes survival of neurons, and blocks growth of new blood vessels in mammals. Defining the molecular phylogeny of PEDF by bioinformatic analysis is one approach to understanding the link between its gene structure and its function in these biological processes. Results From a comprehensive search of available DNA databases we identified a single PEDF gene in all vertebrate species examined. These included four mammalian and six non-mammalian vertebrate species in which PEDF had not previously been described. A five gene cluster around PEDF was found in an approximate 100 kb region in mammals, birds, and amphibians. In ray-finned fish these genes are scattered over three chromosomes although only one PEDF gene was consistently found. The PEDF gene is absent in invertebrates including Drosophila melanogaster (D. melanogaster), Caenorhabditis elegans (C. elegans), and sea squirt (C. intestinalis). The PEDF gene is transcribed in all vertebrate phyla, suggesting it is biologically active throughout vertebrate evolution. The multiple actions of PEDF are likely conserved in evolution since it has the same gene structure across phyla, although the size of the gene ranges from 48.3 kb in X. tropicalis to 2.9 kb in fugu, with human PEDF at a size of 15.6 kb. A strong similarity in the proximal 200 bp of the PEDF promoter in mammals suggests the existence of a possible regulatory region across phyla. Using a non-synonymous/synonymous substitution rate ratio we show that mammalian and fish PEDFs have similar ratios of vertebrates and our studies suggest that the regulation and biological actions of this gene are preserved across vertebrates. This comprehensive analysis of the PEDF gene across phyla provides new information that will aid further characterization of common functional motifs of this serpin in biological processes. PMID:17020603

  16. Molecular phylogeny of the antiangiogenic and neurotrophic serpin, pigment epithelium derived factor in vertebrates

    Directory of Open Access Journals (Sweden)

    Barnstable Colin J

    2006-10-01

    Full Text Available Abstract Background Pigment epithelium derived factor (PEDF, a member of the serpin family, regulates cell proliferation, promotes survival of neurons, and blocks growth of new blood vessels in mammals. Defining the molecular phylogeny of PEDF by bioinformatic analysis is one approach to understanding the link between its gene structure and its function in these biological processes. Results From a comprehensive search of available DNA databases we identified a single PEDF gene in all vertebrate species examined. These included four mammalian and six non-mammalian vertebrate species in which PEDF had not previously been described. A five gene cluster around PEDF was found in an approximate 100 kb region in mammals, birds, and amphibians. In ray-finned fish these genes are scattered over three chromosomes although only one PEDF gene was consistently found. The PEDF gene is absent in invertebrates including Drosophila melanogaster (D. melanogaster, Caenorhabditis elegans (C. elegans, and sea squirt (C. intestinalis. The PEDF gene is transcribed in all vertebrate phyla, suggesting it is biologically active throughout vertebrate evolution. The multiple actions of PEDF are likely conserved in evolution since it has the same gene structure across phyla, although the size of the gene ranges from 48.3 kb in X. tropicalis to 2.9 kb in fugu, with human PEDF at a size of 15.6 kb. A strong similarity in the proximal 200 bp of the PEDF promoter in mammals suggests the existence of a possible regulatory region across phyla. Using a non-synonymous/synonymous substitution rate ratio we show that mammalian and fish PEDFs have similar ratios of Conclusion The PEDF gene first appears in vertebrates and our studies suggest that the regulation and biological actions of this gene are preserved across vertebrates. This comprehensive analysis of the PEDF gene across phyla provides new information that will aid further characterization of common functional motifs of

  17. Honeycomb porous films as permeable scaffold materials for human embryonic stem cell-derived retinal pigment epithelium.

    Science.gov (United States)

    Calejo, Maria Teresa; Ilmarinen, Tanja; Jongprasitkul, Hatai; Skottman, Heli; Kellomäki, Minna

    2016-07-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries, characterised by the degeneration of the retinal pigment epithelium (RPE), a pigmented cell monolayer that closely interacts with the photoreceptors. RPE transplantation is thus considered a very promising therapeutic option to treat this disease. In this work, porous honeycomb-like films are for the first time investigated as scaffold materials for human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). By changing the conditions during film preparation, it was possible to produce films with homogeneous pore distribution and adequate pore size (∼3-5 µm), that is large enough to ensure high permeability but small enough to enable cell adherence and spreading. A brief dip-coating procedure with collagen type IV enabled the homogeneous adsorption of the protein to the walls and bottom of pores, increasing the hydrophilicity of the surface. hESC-RPE adhered and proliferated on all the collagen-coated materials, regardless of small differences in pore size. The differentiation of hESC-RPE was confirmed by the detection of specific RPE protein markers. These results suggest that the porous honeycomb films can be promising candidates for hESC-RPE tissue engineering, importantly enabling the free flow of ions and molecules across the material. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1646-1656, 2016.

  18. Photoacoustic discrimination of vascular and pigmented lesions using classical and Bayesian methods

    Science.gov (United States)

    Swearingen, Jennifer A.; Holan, Scott H.; Feldman, Mary M.; Viator, John A.

    2010-01-01

    Discrimination of pigmented and vascular lesions in skin can be difficult due to factors such as size, subungual location, and the nature of lesions containing both melanin and vascularity. Misdiagnosis may lead to precancerous or cancerous lesions not receiving proper medical care. To aid in the rapid and accurate diagnosis of such pathologies, we develop a photoacoustic system to determine the nature of skin lesions in vivo. By irradiating skin with two laser wavelengths, 422 and 530 nm, we induce photoacoustic responses, and the relative response at these two wavelengths indicates whether the lesion is pigmented or vascular. This response is due to the distinct absorption spectrum of melanin and hemoglobin. In particular, pigmented lesions have ratios of photoacoustic amplitudes of approximately 1.4 to 1 at the two wavelengths, while vascular lesions have ratios of about 4.0 to 1. Furthermore, we consider two statistical methods for conducting classification of lesions: standard multivariate analysis classification techniques and a Bayesian-model-based approach. We study 15 human subjects with eight vascular and seven pigmented lesions. Using the classical method, we achieve a perfect classification rate, while the Bayesian approach has an error rate of 20%.

  19. Optical properties of photoreceptor and retinal pigment epithelium cells investigated with adaptive optics optical coherence tomography

    Science.gov (United States)

    Liu, Zhuolin

    Human vision starts when photoreceptors collect and respond to light. Photoreceptors do not function in isolation though, but share close interdependence with neighboring photoreceptors and underlying retinal pigment epithelium (RPE) cells. These cellular interactions are essential for normal function of the photoreceptor-RPE complex, but methods to assess these in the living human eye are limited. One approach that has gained increased promise is high-resolution retinal imaging that has undergone tremendous technological advances over the last two decades to probe the living retina at the cellular level. Pivotal in these advances has been adaptive optics (AO) and optical coherence tomography (OCT) that together allow unprecedented spatial resolution of retinal structures in all three dimensions. Using these high-resolution systems, cone photoreceptor are now routinely imaged in healthy and diseased retina enabling fundamental structural properties of cones to be studied such as cell spacing, packing arrangement, and alignment. Other important cell properties, however, have remained elusive to investigation as even better imaging performance is required and thus has resulted in an incomplete understanding of how cells in the photoreceptor-RPE complex interact with light. To address this technical bottleneck, we expanded the imaging capability of AO-OCT to detect and quantify more accurately and completely the optical properties of cone photoreceptor and RPE cells at the cellular level in the living human retina. The first objective of this thesis was development of a new AO-OCT method that is more precise and sensitive, thus enabling a more detailed view of the 3D optical signature of the photoreceptor-RPE complex than was previously possible (Chapter 2). Using this new system, the second objective was quantifying the waveguide properties of individual cone photoreceptor inner and outer segments across the macula (Chapter 3). The third objective extended the AO

  20. Regulation of estrogen receptors and MMP-2 expression by estrogens in human retinal pigment epithelium.

    Science.gov (United States)

    Marin-Castaño, Maria E; Elliot, Sharon J; Potier, Mylen; Karl, Michael; Striker, Liliane J; Striker, Gary E; Csaky, Karl G; Cousins, Scott W

    2003-01-01

    Age-related macular degeneration (ARMD) is characterized by progressive thickening and accumulation of various lipid-rich extracellular matrix (ECM) deposits under the retinal pigment epithelium (RPE). ECM dysregulation probably contributes to the pathologic course of ARMD. By activating estrogen receptors (ERs), estrogens regulate the expression of genes relevant in the turnover of ECM, among them matrix metalloproteinase (MMP)-2. Estrogen deficiency may predispose to dysregulated synthesis and degradation of ECM, leading to accumulation of collagens and other proteins between the RPE and its basement membrane. The purposes in the current study were to confirm the expression of ERs in human RPE, to elucidate whether these ERs are functional, and to test whether 17beta-estradiol (E(2)) regulates expression of ERs and MMP-2. Expression of ERs was examined in freshly isolated human RPE monolayer and in cultured human RPE cells, by using total RNA for RT-PCR and protein extracts for Western blot analysis. Supernatants were collected from freshly isolated human RPE and from cultured human RPE to assess MMP-2 activity by zymography and protein expression by Western blot. The transcriptional activity of ERs was studied in transfection experiments with an estrogen-responsive reporter construct. All these studies were preformed in the presence or absence of E(2) (10(-11) and 10(-7) M). Human RPE isolated from female and male individuals expressed both ER subtypes alpha and beta at the mRNA and protein levels. Treatment of cultured RPE cells with 10(-10) M E(2) increased expression of mRNA and protein of both receptor subtypes. E(2) (10(-10) M) also increased MMP-2 activity (approximately 2.2-fold) and protein expression (approximately 2.5-fold). In contrast, there was no change in ER levels and MMP-2 activity at higher E(2) concentrations (10(-8) M), compared with baseline. Preincubation of cells with 10(-7) M pyrrolidinedithiocarbamate (PDTC), an inhibitor of nuclear

  1. Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yanmei Sun

    Full Text Available Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

  2. Early LPS-induced ERK activation in retinal pigment epithelium cells is dependent on PIP 2 -PLC.

    Science.gov (United States)

    Mateos, Melina V; Kamerbeek, Constanza B; Giusto, Norma M; Salvador, Gabriela A

    2016-06-01

    This article presents additional data regarding the study "The phospholipase D pathway mediates the inflammatory response of the retinal pigment epithelium" [1]. The new data presented here show that short exposure of RPE cells to lipopolysaccharide (LPS) induces an early and transient activation of the extracellular signal-regulated kinase (ERK1/2). This early ERK1/2 activation is dependent on phosphatidylinositol bisphosphate-phospholipase C (PIP2-PLC). On the contrary, neither the phospholipase D 1 (PLD1) nor the PLD2 inhibition is able to modulate the early ERK1/2 activation induced by LPS in RPE cells.

  3. Taurine inhibits interleukin-6 expression and release induced by ultraviolet B exposure to human retinal pigment epithelium cells.

    Science.gov (United States)

    Dayang, Wu; Jinsong, Zhang

    2015-01-01

    The massive uptake of compatible osmolytes is a self-protective response shared by retina exposed to hypertonic stress and ultraviolet stress. This study aimed to investigate the protective effects of taurine against ultraviolet damage in human retinal pigment epithelium cells. Real-time PCR, radioimmunoassay, ELISA and immunoassay were used to measure osmolyte uptake and IL-6 expression. Compared with normotonic stress, hypertonic stress led to an induction of osmolyte uptake including betaine, myoinositol and taurine. UVB exposure upregulated osmolyte transporter mRNA expression and increased osmolyte uptake respectively. Especially, taurine suppressed UVB-induced IL-6 mRNA expression significantly. The accumulation of IL-6 in UVB-exposed human retinal pigment epithelial cells supernatant was much slower when the cells were preincubated with taurine. Moreover, taurine suppressed IL-6 concentration in aqueous humour. The effect of compatible osmolyte taurine on IL-6 expression and release may play an important role in cell resistance and adaption to UVB exposure.

  4. Phospholipase D1 modulates protein kinase C-epsilon in retinal pigment epithelium cells during inflammatory response.

    Science.gov (United States)

    Tenconi, Paula E; Giusto, Norma M; Salvador, Gabriela A; Mateos, Melina V

    2016-12-01

    Inflammation is a key factor in the pathogenesis of several retinal diseases. In view of the essential role of the retinal pigment epithelium in visual function, elucidating the molecular mechanisms elicited by inflammation in this tissue could provide new insights for the treatment of retinal diseases. The aim of the present work was to study protein kinase C signaling and its modulation by phospholipases D in ARPE-19 cells exposed to lipopolysaccharide. This bacterial endotoxin induced protein kinase C-α/βII phosphorylation and protein kinase-ε translocation to the plasma membrane in ARPE-19 cells. Pre-incubation with selective phospholipase D inhibitors demonstrated that protein kinase C-α phosphorylation depends on phospholipase D1 and 2 while protein kinase C-ε activation depends only on phospholipase D1. The inhibition of α and β protein kinase C isoforms with Go 6976 did not modify the reduced mitochondrial function induced by lipopolysaccharide. On the contrary, the inhibition of protein kinase C-α, β and ε with Ro 31-8220 potentiated the decrease in mitochondrial function. Moreover, inhibition of protein kinase C-ε reduced Bcl-2 expression and Akt activation and increased Caspase-3 cleavage in cells treated or not with lipopolysaccharide. Our results demonstrate that through protein kinase C-ε regulation, phospholipase D1 protects retinal pigment epithelium cells from lipopolysaccharide-induced damage.

  5. Retbindin is an extracellular riboflavin-binding protein found at the photoreceptor/retinal pigment epithelium interface.

    Science.gov (United States)

    Kelley, Ryan A; Al-Ubaidi, Muayyad R; Naash, Muna I

    2015-02-20

    Retbindin is a novel retina-specific protein of unknown function. In this study, we have used various approaches to evaluate protein expression, localization, biochemical properties, and function. We find that retbindin is secreted by the rod photoreceptors into the inter-photoreceptor matrix where it is maintained via electrostatic forces. Retbindin is predominantly localized at the interface between photoreceptors and retinal pigment epithelium microvilli, a region critical for retinal function and homeostasis. Interestingly, although it is associated with photoreceptor outer segments, retbindin's expression is not dependent on their presence. In vitro, retbindin is capable of binding riboflavin, thus implicating the protein as a metabolite carrier between the retina and the retinal pigment epithelium. Altogether, our data show that retbindin is a novel photoreceptor-specific protein with a unique localization and function. We hypothesize that retbindin is an excellent candidate for binding retinal flavins and possibly participating in their transport from the extracellular space to the photoreceptors. Further investigations are warranted to determine the exact function of retbindin in retinal homeostasis and disease.

  6. Multifocal central serous chorioretinopathy with photoreceptor-retinal pigment epithelium diastasis in heritable pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Li, Xiao Qiang; Pryds, Anders; Carlsen, Jørn;

    2015-01-01

    with clinical examination, enhanced depth optical coherence tomography, fluorescein and indocyanine green angiography, and fundus photography. RESULTS: At presentation, atypical central serous chorioretinopathy with multiple retinal pigment epithelial detachments, a thick subfoveal choroid, and dilated...

  7. The value of reflectance confocal microscopy in diagnosis of flat pigmented facial lesions: a prospective study.

    Science.gov (United States)

    Wurm, E; Pellacani, G; Longo, C; Soyer, H P; Gonzalez, S; Hofmann-Wellenhof, R; Ahlgrimm-Siess, V; Guitera, P; Sinz, C; Kittler, H

    2017-08-01

    Flat pigmented facial lesions are difficult to diagnose even with dermatoscopy. It is controversial how additional information obtained by in vivo reflectance confocal microscopy (RCM) impacts the diagnosis and management. To examine what in vivo reflectance confocal microscopy of flat pigmented facial lesions adds to clinical examination using dermatoscopy including digital dermatoscopic monitoring. We prospectively collected 70 cases of flat pigmented facial lesions and recorded diagnoses and management decisions by experts based on direct clinical examination aided by dermatoscopy including digital dermatoscopic monitoring and by remote experts who reviewed the corresponding confocal images. The expert confocal readers were blinded to the clinical and dermatoscopic appearance of the lesion. The sensitivity of dermatoscopy plus digital dermatoscopic monitoring was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 84.0% (95% CI 70.89% to 92.83%). The sensitivity of RCM was 95.0% (95% CI 75.13% to 99.87%) and the specificity was 82.0% (95% CI 68.56% to 91.42%). Although most flat pigmented facial lesions can be managed by clinical examination and dermatoscopy alone, confocal microscopy is a useful adjunct in selected lesions. If RCM is not correlated with clinical and dermatoscopic information, there is risk of overdiagnosis of actinic keratosis, however. © 2017 European Academy of Dermatology and Venereology.

  8. An ICA-based method for the segmentation of pigmented skin lesions in macroscopic images.

    Science.gov (United States)

    Cavalcanti, Pablo G; Scharcanski, Jacob; Di Persia, Leandro E; Milone, Diego H

    2011-01-01

    Segmentation is an important step in computer-aided diagnostic systems for pigmented skin lesions, since that a good definition of the lesion area and its boundary at the image is very important to distinguish benign from malignant cases. In this paper a new skin lesion segmentation method is proposed. This method uses Independent Component Analysis to locate skin lesions in the image, and this location information is further refined by a Level-set segmentation method. Our method was evaluated in 141 images and achieved an average segmentation error of 16.55%, lower than the results for comparable state-of-the-art methods proposed in literature.

  9. Pigment Epithelium-Derived Factor Reduces Apoptosis and Pro-Inflammatory Cytokine Gene Expression in a Murine Model of Focal Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Yujuan Wang

    2013-10-01

    Full Text Available AMD (age-related macular degeneration is a neurodegenerative disease causing irreversible central blindness in the elderly. Apoptosis and inflammation play important roles in AMD pathogenesis. PEDF (pigment epithelium-derived factor is a potent neurotrophic and anti-inflammatory glycoprotein that protects the retinal neurons and photoreceptors against cell death caused by pathological insults. We studied the effects of PEDF on focal retinal lesions in DKO rd8 (Ccl2 −/− /Cx3cr1 −/− on C57BL/6N [Crb1rd8 ] mice, a model for progressive, focal rd (retinal degeneration. First, we found a significant decrease in PEDF transcript expression in DKO rd8 mouse retina and RPE (retinal pigment epithelium than WT (wild-type, C57BL/6N. Next, cultured DKO rd8 RPE cells secreted lower levels of PEDF protein in the media than WT. Then the right eyes of DKO rd8 mice were injected intravitreously with recombinant human PEDF protein (1 μg, followed by a subconjunctival injection of PEDF (3 μg 4 weeks later. The untreated left eyes served as controls. The effect of PEDF was assessed by fundoscopy, ocular histopathology and A2E {[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl-1E,3E,5E,7E-octatetra-enyl]-1-(2-hydroxyethyl-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl 1E,3E,5E,7E-hexatrienyl]-pyridinium} levels, as well as apoptotic and inflammatory molecules. The PEDF-treated eyes showed slower progression or attenuation of the focal retinal lesions, fewer and/or smaller photoreceptor and RPE degeneration, and significantly lower A2E, relative to the untreated eyes. In addition, lower expression of apoptotic and inflammatory molecules were detected in the PEDF-treated than untreated eyes. Our results establish that PEDF potently stabilizes photoreceptor degeneration via suppression of both apoptotic and inflammatory pathways. The multiple beneficial effects of PEDF represent a novel approach for potential AMD treatment.

  10. Adeno-associated Virus Mediated LacZ Gene Transfect to Cultured Human Iris Pigment Epithelium Cells

    Institute of Scientific and Technical Information of China (English)

    Chun Zhang; Shibo Tang; Yan Luo; Xiaoling Liang; Jing Ma; Shaofen Lin

    2003-01-01

    Purpose: To study the feasibility of adeno-associated virus mediated gene transfection tocultured human iris pigment epithelium (IPE) cells in vitro.Methods: Recombinant replication deficient adeno-associated viruses (AAV) expressingLacZ gene were produced without helper virus. The LacZ gene was transduced into culturedhuman IPE cells.Results: Cultured human IPE cells stained positively anticytokeratin, The titer ofrAAV-LacZ was 2.1 × 108 virus particles/ml, 42% cultured human IPE cells expressedβ-galactosidase 7 days after transfection and 67% after 14 days.Conclusions: Recombined AAV produced without helper virus can transfer a foreign geneinto human IPE cells with high efficiency in vitro.

  11. Automatic detection of subretinal fluid and sub-retinal pigment epithelium fluid in optical coherence tomography images.

    Science.gov (United States)

    Ding, Weiguang; Young, Mei; Bourgault, Serge; Lee, Sieun; Albiani, David A; Kirker, Andrew W; Forooghian, Farzin; Sarunic, Marinko V; Merkur, Andrew B; Beg, Mirza Faisal

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Subretinal fluid (SRF) and sub-retinal pigment epithelium (sub-RPE) fluid are signs of AMD and can be detected in optical coherence tomography images. However, manual detection and segmentation of SRFs and sub-RPE fluids are laborious and time consuming. In this paper, a novel pipeline is proposed for automatic detection of SRFs and sub-RPE fluids. First, top and bottom layers of retina are segmented using a graph cut method. Then, a Split Bregman-based segmentation method is used to segment dark regions between layers. These segmented regions are considered as potential fluid candidates, on which a set of features are generated. After that, a random forest classifier is trained to distinguish between the true fluid regions from the falsely detected fluid regions. This method shows reasonable performance in a leave-one-out evaluation using a dataset from 21 patients.

  12. Noninvasive two-photon microscopy imaging of mouse retina and retinal pigment epithelium through the pupil of the eye.

    Science.gov (United States)

    Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Hunter, Jennifer J; Williams, David R; Alexander, Nathan S; Palczewski, Krzysztof

    2014-07-01

    Two-photon excitation microscopy can image retinal molecular processes in vivo. Intrinsically fluorescent retinyl esters in subcellular structures called retinosomes are an integral part of the visual chromophore regeneration pathway. Fluorescent condensation products of all-trans-retinal accumulate in the eye with age and are also associated with age-related macular degeneration (AMD). Here, we report repetitive, dynamic imaging of these compounds in live mice through the pupil of the eye. By leveraging advanced adaptive optics, we developed a data acquisition algorithm that permitted the identification of retinosomes and condensation products in the retinal pigment epithelium by their characteristic localization, spectral properties and absence in genetically modified or drug-treated mice. This imaging approach has the potential to detect early molecular changes in retinoid metabolism that trigger light- and AMD-induced retinal defects and to assess the effectiveness of treatments for these conditions.

  13. OCT and in vivo confocal microscopy of a pigmented corneal tumor-like lesion.

    Science.gov (United States)

    Szaflik, Jacek P; Oldak, Monika; Ulinska, Magdalena; Ulnska, Magdalena; Tesla, Piotr; Szaflik, Jerzy

    2009-01-01

    A 43-year-old woman presented with a pigmented flat tumor situated at the posterior surface of the cornea nasally in her left eye. Anterior-segment optical coherence tomography revealed that the lesion was similar to the iris leaf, was limited to the cornea, and did not communicate with the iridocorneal angle. In vivo scanning slit confocal microscopy imaged dense hyperreflective tissue behind the endothelium and bright spots dispersed on the adjacent endothelial surface. Multiple hyporeflective formations resembling cell nuclei were visualized within the hyperreflective mass and the cell borders were distinguished. The diagnosis of pigmented nevus or retrocorneal membrane was suspected. The authors conclude that anterior-segment optical coherence tomography and in vivo scanning slit confocal microscopy are useful in assessing the microstructure and penetration of pigmented corneal lesions.

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

    Science.gov (United States)

    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

  15. The impact of cHS4 insulators on DNA transposon vector mobilization and silencing in retinal pigment epithelium cells.

    Directory of Open Access Journals (Sweden)

    Nynne Sharma

    Full Text Available DNA transposons have become important vectors for efficient non-viral integration of transgenes into genomic DNA. The Sleeping Beauty (SB, piggyBac (PB, and Tol2 transposable elements have distinct biological properties and currently represent the most promising transposon systems for animal transgenesis and gene therapy. A potential obstacle, however, for persistent function of integrating vectors is transcriptional repression of the element and its genetic cargo. In this study we analyze the insulating effect of the 1.2-kb 5'-HS4 chicken β-globin (cHS4 insulator element in the context of SB, PB, and Tol2 transposon vectors. By examining transgene expression from genomically inserted transposon vectors encoding a marker gene driven by a silencing-prone promoter, we detect variable levels of transcriptional silencing for the three transposon systems in retinal pigment epithelium cells. Notably, the PB system seems less vulnerable to silencing. Incorporation of cHS4 insulator sequences into the transposon vectors results in 2.2-fold and 1.5-fold increased transgene expression levels for insulated SB and PB vectors, respectively, but an improved persistency of expression was not obtained for insulated transgenes. Colony formation assays and quantitative excision assays unveil enhanced SB transposition efficiencies by the inclusion of the cHS4 element, resulting in a significant increase in the stable transfection rate for insulated SB transposon vectors in human cell lines. Our findings reveal a positive impact of cHS4 insulator inclusion for SB and PB vectors in terms of increased transgene expression levels and improved SB stable transfection rates, but also the lack of a long-term protective effect of the cHS4 insulator against progressive transgene silencing in retinal pigment epithelium cells.

  16. Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy.

    Science.gov (United States)

    Loegl, Jelena; Nussbaumer, Erika; Hiden, Ursula; Majali-Martinez, Alejandro; Ghaffari-Tabrizi-Wizy, Nassim; Cvitic, Silvija; Lang, Ingrid; Desoye, Gernot; Huppertz, Berthold

    2016-07-01

    The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto-placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti-angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF.

  17. Bimonthly half-dose ranibizumab in large pigment epithelial detachment and retinal angiomatous proliferation with high risk of retinal pigment epithelium tear: a case report

    Directory of Open Access Journals (Sweden)

    Monés J

    2013-06-01

    Full Text Available Jordi Monés,1,2 Marc Biarnés,1 Josep Badal11Institut de la Màcula i de la Retina, Barcelona, Spain; 2Barcelona Macula Foundation, Barcelona, SpainIntroduction: The management of large pigment epithelial detachments (PEDs associated with retinal angiomatous proliferation (RAP remains a challenge due to the high risk of retinal pigment epithelial (RPE tear. We describe the successful progressive anatomical result and the maintenance of visual acuity to bimonthly, half-dose ranibizumab in a patient with this condition.Purpose: To describe the management of a large PED secondary to RAP with bimonthly, half-dose ranibizumab.Method: Case report.Patient: A 71-year-old woman presented with visual symptoms due to an enlarged PED, compared with previous visits, secondary to a RAP lesion, with a visual acuity of 20/32. To reduce the risk of an RPE tear and a significant decrease in vision, we discussed with the patient the possibility of treating the lesion in a progressive manner, with more frequent but smaller doses of ranibizumab. The patient was treated biweekly with 0.25 mg of ranibizumab until flattening of the PED.Results: The large PED flattened progressively, and visual acuity was preserved with no adverse events.Discussion: The use of half-dose antiangiogenic therapy may be useful in managing large vascularized PED associated with RAP, in an attempt to reduce the risk of RPE tear.Keywords: age-related macular degeneration, pigment epithelial detachment, ranibizumab, retinal angiomatous proliferation, RPE tear

  18. Bystander effects elicited by single-cell photo-oxidative blue-light stimulation in retinal pigment epithelium cell networks

    Science.gov (United States)

    Ishii, Masaaki; Rohrer, Bärbel

    2017-01-01

    ‘Bystander effect’ refers to the induction of biological effects in cells not directly targeted. The retinal pigment epithelium consists of hexagonal cells, forming a monolayer interconnected by gap junctions (GJs). Oxidative stress initiated in an individual cell by photostimulation (488 nm) triggered changes in reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential (ψm). The Ca2+ signal was transmitted to neighboring cells slowly and non-uniformly; the ROS signal spread fast and radially. Increased Ca2+ levels were associated with a loss in ψm. GJ blockers prevented the spreading of the Ca2+, but not the ROS-related signal. The GJ-mediated Ca2+ wave was associated with cell death by 24 h, requiring endoplasmic reticulum–mitochondria Ca2+ transfer. Ensuing cell death was correlated with baseline Ca2+ levels, and baseline Ca2+ levels were correlated with pigmentation. Hence, local oxidative stress in a donor cell can trigger changes in certain connected recipient cells, a signal that required GJ communication and an ROS-Ca2+ dual-hit. Finally, damage apparently occurred in susceptible cells, which correlated with baseline Ca2+ levels. PMID:28179989

  19. Photoreceptors repair by autologous transplantation of retinal pigment epithelium and partial-thickness choroid graft in rabbits.

    Science.gov (United States)

    Zhang, Taoran; Hu, Yuntao; Li, Ying; Wu, Jianguo; Zhao, Lin; Wang, Changguan; Liu, Yuling; Yin, Zhengqin; Ma, Zhizhong

    2009-06-01

    To investigate whether autologous retinal pigment epithelium (RPE) and a partial-thickness graft can repair degenerated photoreceptors overlying a mechanically damaged Bruch's membrane. Twenty-one pigmented rabbits were used in the study. Abrasive debridement of the RPE was performed with a metal cannula after superior retinal bleb detachment in 20 rabbits. The graft was prepared beneath the inferior retina and was transplanted to the debridement area 14 days later. Debridement-only sites served as the control. Tissue sections were evaluated by light microscopy and transmission electron microscopy at 7 days, 1 month, and 3 months after transplantation, corresponding to 21 days, 45 days, and 3 months after debridement, respectively. When analyzed at 7 days after transplantation, short buds of inner segment with regularly organized outer nuclear layer were observed. The outer segments (OS) were of insufficient length to be observed, but by 1 and 3 months, a significant elongation of the OS was detected. In control retinas from 21 days (corresponding to 7 days after transplantation) to 3 months after RPE debridement, the outer nuclear layer cells were disorganized and diminished. This study showed that autologous RPE and partial-thickness choroid graft have the capacity not only to support photoreceptor cell survival, but also to initiate early repair mechanisms, as exhibited by outer segment regeneration.

  20. Clinical studies of pigmented lesions in human skin by using a multiphoton tomograph

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    Balu, Mihaela; Kelly, Kristen M.; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.

    2013-02-01

    In vivo imaging of pigmented lesions in human skin was performed with a clinical multiphoton microscopy (MPM)-based tomograph (MPTflex, JenLab, Germany). Two-photon excited fluorescence was used for visualizing endogenous fluorophores such as NADH/FAD, keratin, melanin in the epidermal cells and elastin fibers in the dermis. Collagen fibers were imaged by second harmonic generation. Our study involved in vivo imaging of benign melanocytic nevi, atypical nevi and melanoma. The goal of this preliminary study was to identify in vivo the characteristic features and their frequency in pigmented lesions at different stages (benign, atypical and malignant) and to evaluate the ability of in vivo MPM to distinguish atypical nevi from melanoma. Comparison with histopathology was performed for the biopsied lesions. Benign melanocytic nevi were characterized by the presence of nevus cell nests at the epidermal-dermal junction. In atypical nevi, features such as lentiginous hyperplasia, acanthosis and architectural disorder were imaged. Cytological atypia was present in all the melanoma lesions imaged, showing the strongest correlation with malignancy. The MPM images demonstrated very good correlation with corresponding histological images, suggesting that MPM could be a promising tool for in vivo non-invasive pigmented lesion diagnosis, particularly distinguishing atypical nevi from melanoma.

  1. Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD

    Science.gov (United States)

    Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2016-01-01

    Background/aims To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Methods Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Results Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). Conclusions PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. PMID:26183936

  2. Fine structure of the retinal pigment epithelium in the Port Jackson shark (Heterodontus phillipi).

    Science.gov (United States)

    Braekevelt, C R

    1994-11-01

    The structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by light and electron microscopy in the Port Jackson shark (Heterodontus phillipi). In this elasmobranch the RPE consists of a single layer of low cuboidal cells which show basal (scleral) infolding and apical (vitreal) processes that enclose photoreceptor outer segments. Laterally these epithelial cells are joined by a series of apically located tight junctions. The RPE cells display a large vesicular nucleus, abundant smooth endoplasmic reticulum as well as numerous polysomes and mitochondria. Phagosomes are present, rough endoplasmic reticulum is scarce and myeloid bodies were not observed. Melanosomes are absent over the choroidally located tapetum lucidum, but are not abundant even in extratapetal areas. This paucity of melanosomes probably makes retinomotor movements unimportant. Bruch's membrane or complexus basalis is a pentalaminate structure. The endothelium of the choriocapillaris is thin but minimally fenestrated.

  3. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice.

    Science.gov (United States)

    Feng, Dilu; Menger, Michael D; Wang, Hongbo; Laschke, Matthias W

    2014-02-01

    In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE(+)) and without luminal epithelium (LE(-)) were transplanted from transgenic green-fluorescent-protein-positive (GFP(+)) donor mice into the dorsal skinfold chamber of GFP(-) wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE(-) fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE(+) fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE(+) lesions compared with LE(-) lesions. In addition, we found that many GFP(+) microvessels grew outside the LE(-) lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  4. Luminal epithelium in endometrial fragments affects their vascularization, growth and morphological development into endometriosis-like lesions in mice

    Directory of Open Access Journals (Sweden)

    Dilu Feng

    2014-02-01

    Full Text Available In endometriosis research, endometriosis-like lesions are usually induced in rodents by transplantation of isolated endometrial tissue fragments to ectopic sites. In the present study, we investigated whether this approach is affected by the cellular composition of the grafts. For this purpose, endometrial tissue fragments covered with luminal epithelium (LE+ and without luminal epithelium (LE− were transplanted from transgenic green-fluorescent-protein-positive (GFP+ donor mice into the dorsal skinfold chamber of GFP− wild-type recipient animals to analyze their vascularization, growth and morphology by means of repetitive intravital fluorescence microscopy, histology and immunohistochemistry during a 14-day observation period. LE− fragments developed into typical endometriosis-like lesions with cyst-like dilated endometrial glands and a well-vascularized endometrial stroma. In contrast, LE+ fragments exhibited a polypoid morphology and a significantly reduced blood perfusion after engraftment, because the luminal epithelium prevented the vascular interconnection with the microvasculature of the surrounding host tissue. This was associated with a markedly decreased growth rate of LE+ lesions compared with LE− lesions. In addition, we found that many GFP+ microvessels grew outside the LE− lesions and developed interconnections to the host microvasculature, indicating that inosculation is an important mechanism in the vascularization process of endometriosis-like lesions. Our findings demonstrate that the luminal epithelium crucially affects the vascularization, growth and morphology of endometriosis-like lesions. Therefore, it is of major importance to standardize the cellular composition of endometrial grafts in order to increase the validity and reliability of pre-clinical rodent studies in endometriosis research.

  5. Comparing in vivo pump-probe and multiphoton fluorescence microscopy of melanoma and pigmented lesions

    Science.gov (United States)

    Wilson, Jesse W.; Degan, Simone; Gainey, Christina S.; Mitropoulos, Tanya; Simpson, Mary Jane; Zhang, Jennifer Y.; Warren, Warren S.

    2015-05-01

    We demonstrate a multimodal approach that combines a pump-probe with confocal reflectance and multiphoton autofluorescence microscopy. Pump-probe microscopy has been proven to be of great value in analyzing thin tissue sections of pigmented lesions, as it produces molecular contrast which is inaccessible by other means. However, the higher optical intensity required to overcome scattering in thick tissue leads to higher-order nonlinearities in the optical response of melanin (e.g., two-photon pump and one-photon probe) that present additional challenges for interpreting the data. We show that analysis of pigment composition in vivo must carefully account for signal terms that are nonlinear with respect to the pump and probe intensities. We find that pump-probe imaging gives useful contrast for pigmented structures over a large range of spatial scales (100 μm to 1 cm), making it a potentially useful tool for tracking the progression of pigmented lesions without the need to introduce exogenous contrast agents.

  6. Effects of Nerve Growth Factor on Proliferation and DNA Synthesis of Cultured Human Fetal Retinal Pigment Epithelium Cells

    Institute of Scientific and Technical Information of China (English)

    Wensheng Li; Jun Wen; Deyong Jiang; Jianguang Ding

    2002-01-01

    Objective: To investigate the effects of nerve growth factor(NGF)on proliferation and DNAthesis of cultured human fetal retinal pigment epithelium (RPE)cells in vitro.Methods: Primary culture and subculture of human fetal retinal pigment epithelium cellswere established in vitro first. Cultured RPE cells were treated with NGF by variousconcentrations 0μg/L, 50μg/L, 100μg/L, 200μg/L and 300μg/L(final concentration)for 48 hs.After 48 hs, cells proliferation was measured with methyl thiazolyl tetrazolium(MTT)assay method and the amount of DNA was determined by the absorbance at 280nm of nucleic acid & protein analysis.Results: The A values of 100 μg/L, 200 μg/L, 300 μg/L NGF was(0. 213 7 ± 0. 23 3),(0. 218 8 ±0. 018 1), (0. 232 2 ±0. 016 4) as compared with(0. 189 7 ±0. 015 2) of Avalue of 0 μg/L NGF respectively, q value was 3.63,4.40, 6. 42 and P value was0. 015, 0. 000, 0. 000(q-test). The DNA concentrations of 100 μg/L, 200 μg/L, 300μg/L and 400 μg/L NGF was (981. 220 4 ± 123.535 7), (1 375. 848 4 ±244. 471 8),(1 658.707 1 ± 176. 938 1), (2 353.086 3 ±609. 906 4) μg/ml as compared with(666. 818 8 ± 141. 330 2) μg/ml of DNA concentration of 0 μg/L NGF respectively, qvalue was 3.63,8.20,11.47,19.46, P value was 0. 024,0. 000,0. 000,0. 000 (q-test).Conclusion: The data suggested that NGF could stimulate the proliferation and DNAsynthesis of cultured of hRPE cells in vitro in a dose-dependent manner.

  7. Effect of Hypericin on Confocal Imaging of Ca2+ Signaling in Cultured Human Retinal Pigment Epithelium

    Institute of Scientific and Technical Information of China (English)

    Qianying Gao; Yannian Hui; Yusheng Wang; Lin Wang

    2001-01-01

    Purpose: To investigate the mechanism of the Ca2 + signaling in cultured human retinal pigment epithelial(RPE) cells with the protein kinase C(PKC) specific inhibitor-hypericin stimulation.Methods: Cultured human RPE cells were analyzed using the fluorescence Ca2+ dye fluo-3 AM and laser scanning confocal microscope(LSCM) after stimulation with 100nM phorbol 12-myristate 13-acetate(PMA) and (or)5 concentrations of hypericin(1, 2, 3, 4 and 5 μM).Results: The normal fluorescence in RPE cells was strong and distributed throughout the cells. The nucleus appeared to be more fluorescent than the cytoplasm. After stimulation with PMA alone or 5 concentrations of hypericin, a rapid decrease in flurescence intensity was observed. There was no obvious difference in decreased curve among 5concentrations. However, after stimulation with a 24 hr preincubation of PMA and 5 concentrations of hypericin, a further decrease was not observed.Conclusion: Fluo-3 AM appears to be a good indicator of the change in Ca2+ occurring in RPE cells and hypericin is a strong inhibitor of Ca2 + influx channel. Hypericin has potential as a therapeutic drug for proliferative vitreoretinopathy(PVR), the inhibitory effect on PVR might be caused by blocking the PKC activity and inhibiting Ca2+ influxpathway.

  8. Effects of vegetable oils on biochemical and biophysical properties of membrane retinal pigment epithelium cells.

    Science.gov (United States)

    Said, Toihiri; Tremblay-Mercier, Jennifer; Berrougui, Hicham; Rat, Patrice; Khalil, Abdelouahed

    2013-10-01

    The aim of this study was to investigate the effect of vegetable oil enrichment of retinal pigment epithelial (RPE) cells on their biochemical and biophysical properties. For this, RPE cells were incubated with 4 different vegetables oils (olive oil, corn oil, argan oil, and camelina oil). The cytotoxicity of these vegetable oils was assessed in vivo on 8-week-old mice and in vitro by using the neutral red and YO-PRO-1 tests. Membrane fluidity was evaluated by fluorescence anisotropy using the fluorescent probe diphenylhexatriene, and membrane fatty acid composition was assessed by gas chromatography. None of the oils tested displayed cytotoxic effects. In vitro, omega-3 rich oils improved membrane fluidity by 47% compared with the control cells. The omega-3 PUFA content within membranes decreased by 38% to 55% when cells were incubated separately with olive oil, corn oil, or argan oil, and increased when cells were incubated with a mixture of those oils, or with camelina oil alone (50% and 103% increase, respectively). Our results show that the fatty acids in vegetable oil incorporate into retinal cells and increase the plasma membrane fluidity.

  9. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

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    Selina Beasley

    2014-01-01

    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  10. iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study

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    Peter D. Westenskow

    2016-01-01

    Full Text Available Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD, a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.

  11. Progressive atrophy of retinal pigment epithelium after trypan-blue-assisted ILM peeling for macular hole surgery

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    Sachin Jain

    2013-01-01

    Full Text Available We report a case of progressive atrophy of the retinal pigment epithelium (RPE after trypan-blue-assisted peeling of internal limiting membrane (ILM for macular hole surgery. A 68-year-old Caucasian female underwent a 20-g pars plana vitrectomy for a chronic stage-3 macular hole. The ILM was stained with 0.06% trypan blue (VisionBlue™, DORC Netherlands for 2 min after fluid air exchange. Dye was reapplied for another 2 min due to poor staining. The ILM was completely removed around the macular hole with forceps. RPE atrophy was noticed at the edge of the hole 1 month after surgery. It progressively increased in intensity and enlarged over 2 years. Her final visual acuity was counting fingers, significantly worse compared to her presenting visual acuity of 20/200. Progressive atrophy of RPE in our patient was most likely due to the toxicity of trypan blue. Reapplication of the dye may increase the likelihood of toxicity.

  12. Peroxidation stimulated by lipid hydroperoxides on bovine retinal pigment epithelium mitochondria: effect of cellular retinol-binding protein.

    Science.gov (United States)

    Terrasa, Ana M; Guajardo, Margarita H; Catalá, Angel

    2003-07-01

    This study analyzes the effect of cellular retinol-binding protein (CRBP), partially purified from retinal pigment epithelium (RPE) cytosol, on the non-enzymatic lipid peroxidation induced by fatty acid hydroperoxides of mitochondrial membranes isolated from bovine RPE. The effect of different amounts (50, 75 and 100 nmol) of linoleic acid hydroperoxide (LHP), arachidonic acid hydroperoxide (AHP) and docosahexaenoic acid hydroperoxide (DHP) on the lipid peroxidation of RPE mitochondria was studied; RPE mitochondria deprived of exogenously added hydroperoxide was utilized as control. The process was measured simultaneously by determining chemiluminescence as well as polyunsaturated fatty acid (PUFA) degradation of total lipids isolated from RPE mitochondria. The addition of hydroperoxides to RPE mitochondria produces a marked increase in light emission that was hydroperoxide concentration dependent. The highest value of activation was produced by LHP. The major difference in the fatty acid composition of total lipids isolated from native and peroxidized RPE mitochondria incubated with and without hydroperoxides was found in the docosahexaenoic acid content, this decreased 40.90+/-3.01% in the peroxidized group compared to native RPE mitochondria. The decrease was significantly high: 86.32+/-2.57% when the lipid peroxidation was stimulated by 100 nmol of LHP. Inhibition of lipid peroxidation (decrease of chemiluminescence) was observed with the addition of increasing amounts (100-600 microg) of CRBP to RPE mitochondria. The inhibitory effect reaches the highest values in the presence of LHP.

  13. Retinal pigment epithelium cell-derived exosomes: Possible relevance to CNV in wet-age related macular degeneration.

    Science.gov (United States)

    Tong, Yao; Zhou, Ya-Li; Wang, Yi-Xiao; Zhao, Pei-Quan; Wang, Zhao-Yang

    2016-12-01

    Exosomes are small vesicles that are released by almost every cell type and play a crucial role in many physiological and pathological processes associated with different diseases. Specifically, they promote angiogenesis in the pathogenesis of some diseases. According to previous research, the proteins of exosomes taken from the aqueous humor (AH) of patients with wet-age related macular degeneration (AMD) may function as a new diagnostic biomarker of AMD, suggesting that exosomes may play an important role in the occurrence and development of choroidal neovascularization (CNV). Moreover, additional research has revealed that the levels of some protein makers of exosomes are up-regulated in aged retinal pigment epithelium (RPE) and that drusen and oxidative stress may promote the secretion of exosomes derived from RPE cells. Consequently, we hypothesize that RPE cell-derived exosomes may be relevant to CNV in wet AMD. If this hypothesis is proven correct, future studies based on this link may also help to elucidate the molecular mechanisms of wet AMD and to find new therapeutic targets for the treatment of AMD.

  14. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    Science.gov (United States)

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  15. Fucoidan reduces secretion and expression of vascular endothelial growth factor in the retinal pigment epithelium and reduces angiogenesis in vitro.

    Directory of Open Access Journals (Sweden)

    Michaela Dithmer

    Full Text Available Fucoidan is a polysaccharide isolated from brown algae which is of current interest for anti-tumor therapy. In this study, we investigated the effect of fucoidan on the retinal pigment epithelium (RPE, looking at physiology, vascular endothelial growth factor (VEGF secretion, and angiogenesis, thus investigating a potential use of fucoidan for the treatment of exudative age-related macular degeneration. For this study, human RPE cell line ARPE-19 and primary porcine RPE cells were used, as well as RPE/choroid perfusion organ cultures. The effect of fucoidan on RPE cells was investigated with methyl thiazolyl tetrazolium--assay, trypan blue exclusion assay, phagocytosis assay and a wound healing assay. VEGF expression was evaluated in immunocytochemistry and Western blot, VEGF secretion was evaluated in ELISA. The effect of fucoidan on angiogenesis was tested in a Matrigel assay using calcein-AM vital staining, evaluated by confocal laser scanning microcopy and quantitative image analysis. Fucoidan displays no toxicity and does not diminish proliferation or phagocytosis, but reduces wound healing in RPE cells. Fucoidan decreases VEGF secretion in RPE/choroid explants and RPE cells. Furthermore, it diminishes VEGF expression in RPE cells even when co-applied with bevacizumab. Furthermore, fucoidan reduces RPE-supernatant- and VEGF-induced angiogenesis of peripheral endothelial cells. In conclusion, fucoidan is a non-toxic agent that reduces VEGF expression and angiogenesis in vitro and may be of interest for further studies as a potential therapy against exudative age-related macular degeneration.

  16. Deriving retinal pigment epithelium (RPE) from induced pluripotent stem (iPS) cells by different sizes of embryoid bodies.

    Science.gov (United States)

    Muñiz, Alberto; Ramesh, Kaini R; Greene, Whitney A; Choi, Jae-Hyek; Wang, Heuy-Ching

    2015-02-04

    Pluripotent stem cells possess the ability to proliferate indefinitely and to differentiate into almost any cell type. Additionally, the development of techniques to reprogram somatic cells into induced pluripotent stem (iPS) cells has generated interest and excitement towards the possibility of customized personal regenerative medicine. However, the efficiency of stem cell differentiation towards a desired lineage remains low. The purpose of this study is to describe a protocol to derive retinal pigment epithelium (RPE) from iPS cells (iPS-RPE) by applying a tissue engineering approach to generate homogenous populations of embryoid bodies (EBs), a common intermediate during in vitro differentiation. The protocol applies the formation of specific size of EBs using microwell plate technology. The methods for identifying protein and gene markers of RPE by immunocytochemistry and reverse-transcription polymerase chain reaction (RT-PCR) are also explained. Finally, the efficiency of differentiation in different sizes of EBs monitored by fluorescence-activated cell sorting (FACS) analysis of RPE markers is described. These techniques will facilitate the differentiation of iPS cells into RPE for future applications.

  17. Phloroglucinol protects retinal pigment epithelium and photoreceptor against all-trans-retinal-induced toxicity and inhibits A2E formation.

    Science.gov (United States)

    Cia, David; Cubizolle, Aurélie; Crauste, Céline; Jacquemot, Nathalie; Guillou, Laurent; Vigor, Claire; Angebault, Claire; Hamel, Christian P; Vercauteren, Joseph; Brabet, Philippe

    2016-09-01

    Among retinal macular diseases, the juvenile recessive Stargardt disease and the age-related degenerative disease arise from carbonyl and oxidative stresses (COS). Both stresses originate from an accumulation of all-trans-retinal (atRAL) and are involved in bisretinoid formation by condensation of atRAL with phosphatidylethanolamine (carbonyl stress) in the photoreceptor and its transformation into lipofuscin bisretinoids (oxidative stress) in the retinal pigment epithelium (RPE). As atRAL and bisretinoid accumulation contribute to RPE and photoreceptor cell death, our goal is to select powerful chemical inhibitors of COS. Here, we describe that phloroglucinol, a natural phenolic compound having anti-COS properties, protects both rat RPE and mouse photoreceptor primary cultures from atRAL-induced cell death and reduces hydrogen peroxide (H2 O2 )-induced damage in RPE in a dose-dependent manner. Mechanistic analyses demonstrate that the protective effect encompasses decrease in atRAL-induced intracellular reactive oxygen species and free atRAL levels. Moreover, we show that phloroglucinol reacts with atRAL to form a chromene adduct which prevents bisretinoid A2E synthesis in vitro. Taken together, these data show that the protective effect of phloroglucinol correlates with its ability to trap atRAL and to prevent its further transformation into deleterious bisretinoids. Phloroglucinol might be a good basis to develop efficient therapeutic derivatives in the treatment of retinal macular diseases.

  18. Novel localization of peripherin 2, the photoreceptor-specific retinal degeneration slow protein, in retinal pigment epithelium.

    Science.gov (United States)

    Uhl, Patrizia B; Amann, Barbara; Hauck, Stefanie M; Deeg, Cornelia A

    2015-01-26

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis.

  19. Alzheimer's disease: Elevated pigment epithelium-derived factor in the cerebrospinal fluid is mostly of systemic origin.

    Science.gov (United States)

    Lang, Veronika; Zille, Marietta; Infante-Duarte, Carmen; Jarius, Sven; Jahn, Holger; Paul, Friedemann; Ruprecht, Klemens; Pina, Ana Luisa

    2017-04-15

    Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19). We established CSF/serum quotient diagrams to determine the fraction of intrathecally synthesized PEDF in CSF. We found that PEDF is significantly increased in CSF of patients with AD, FTD, and bacterial meningitis. Remarkably, PEDF concentrations were also significantly elevated in serum of patients with AD. CSF/serum quotient diagrams demonstrated that elevated PEDF concentrations in CSF of patients with AD are mostly due to elevated PEDF concentrations in serum. These findings underscore the importance of relating concentrations of proteins in CSF to their respective concentrations in serum to avoid erroneous interpretations of increased protein concentrations in lumbar CSF.

  20. G-quartet oligonucleotide mediated delivery of proteins into photoreceptors and retinal pigment epithelium via intravitreal injection.

    Science.gov (United States)

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2016-04-01

    There is currently no available method to efficiently deliver proteins across the plasma membrane of photoreceptor or retinal pigment epithelium (RPE) cells in vivo. Thus, current clinical application of recombinant proteins in ophthalmology is limited to the use of proteins that perform their biological function extracellularly. The ability to traverse biological membranes would enable the mobilization of a significantly larger number of proteins with previously well characterized properties. Nucleolin is abundantly present on the surface of rapidly dividing cells including cancer cells. Surprisingly, nucleolin is also present on the surface of photoreceptor cell bodies. Here we investigated whether nucleolin can be utilized as a gateway for the delivery of proteins into retinal cells following intravitreal injection. AS1411 is a G-quartet aptamer capable of targeting nucleolin. Subsequent to intravitreal injection, fluorescently labeled AS1411 localized to various retinal cell types including the photoreceptors and RPE. AS1411 linked to streptavidin (a ∼50 kDa protein) via a biotin bridge enabled the uptake of Streptavidin into photoreceptors and RPE. AS1411-Streptavidin conjugate applied topically to the cornea allowed for uptake of the conjugate into the nucleus and cytoplasm of corneal endothelial cells. Clinical relevance of AS1411 as a delivery vehicle was strongly indicated by demonstration of the presence of cell surface nucleolin on the photoreceptors, inner neurons and ganglion cells of human retina. These data support exploration of AS1411 as a means of delivering therapeutic proteins to diseased retina.

  1. Pigment epithelium-derived factor: clinical significance in estrogen-dependent tissues and its potential in cancer therapy

    Science.gov (United States)

    Franco-Chuaire, María Liliana; Ramírez-Clavijo, Sandra; Chuaire-Noack, Lilian

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of non-inhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and anti-metastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF. PMID:26523216

  2. Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma

    Directory of Open Access Journals (Sweden)

    Asunción Fernández-Barral

    2014-06-01

    Full Text Available Pigment epithelium-derived factor (PEDF, a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

  3. Light-induced damage and its diagnosis in two-photon excited autofluorescence imaging of retinal pigment epithelium cells

    Science.gov (United States)

    Chen, Danni; Qu, Junle; Xu, Gaixia; Zhao, Lingling; Niu, Hanben

    2007-05-01

    In this paper, a novel method for the differentiation of the retinal pigment epithelium (RPE) cells after light-induced damage by two-photon excitation is presented. Fresh samples of RPE cells of pig eyes are obtained from local slaughterhouse. Light-induced damage is produced by the output from Ti: sapphire laser which is focused onto the RPE layer. We study the change of the autofluorescence properties of RPE after two-photon excitation with the same wavelength. Preliminary results show that after two-photon excitation, there are two clear changes in the emission spectrum. The first change is the blue-shift of the emission peak. The emission peak of the intact RPE is located at 592nm, and after excitation, it shifts to 540nm. It is supposed that the excitation has led to the increased autofluorescence of flavin whose emission peak is located at 540nm. The second change is the increased intensity of the emission peak, which might be caused by the accelerated aging because the autofluorescence of RPE would increase during aging process. Experimental results indicate that two-photon excitation could not only lead to the damage of the RPE cells in multiphoton RPE imaging, but also provide an evaluation of the light-induced damage.

  4. Recombinant human pigment epithelium-derived factor (PEDF): characterization of PEDF overexpressed and secreted by eukaryotic cells.

    Science.gov (United States)

    Stratikos, E.; Alberdi, E.; Gettins, P. G.; Becerra, S. P.

    1996-01-01

    Pigment epithelium-derived factor (PEDF) is a serpin found in the interphotoreceptor matrix of the eye, which, although not a proteinase inhibitor, possesses a number of important biological properties, including promotion of neurite outgrowth and differential expression in quiescent versus senescent states of certain cell types. The low amounts present in the eye, together with the impracticality of using the eye as a source for isolation of the human protein, make it important to establish a system for overexpression of the recombinant protein for biochemical and biological studies. We describe here the expression and secretion of full-length glycosylated human recombinant PEDF at high levels (> 20 micrograms/ mL) into the growth medium of baby hamster kidney cells and characterization of the purified rPEDF by circular dichroism and fluorescence spectroscopies and neurite outgrowth assay. By these assays, the recombinant protein behaves as expected for a correctly folded full-length human PEDF. The availability of milligram amounts of PEDF has permitted quantitation of its heparin binding properties and of the effect of reactive center cleavage on the stability of PEDF towards thermal and guanidine hydrochloride denaturation. PMID:8976566

  5. Glycosaminoglycans in human retinoblastoma cells: Heparan sulfate, a modulator of the pigment epithelium-derived factor-receptor interactions

    Science.gov (United States)

    Alberdi, Elena M; Weldon, John E; Becerra, S Patricia

    2003-01-01

    Background Pigment epithelium-derived factor (PEDF) has binding affinity for cell-surface receptors in retinoblastoma cells and for glycosaminoglycans. We investigated the effects of glycosaminoglycans on PEDF-receptor interactions. Results 125I-PEDF formed complexes with protease-resistant components of medium conditioned by human retinoblastoma Y-79 cells. Using specific glycosaminoglycan degrading enzymes in spectrophotometric assays and PEDF-affinity chromatography, we detected heparin and heparan sulfate-like glycosaminoglycans in the Y-79 conditioned media, which had binding affinity for PEDF. The Y-79 conditioned media significantly enhanced the binding of 125I-PEDF to Y-79 cell-surface receptors. However, enzymatic and chemical depletion of sulfated glycosaminoglycans from the Y-79 cell cultures by heparitinase and chlorate treatments decreased the degree of 125I-PEDF binding to cell-surface receptors. Conclusions These data indicate that retinoblastoma cells secrete heparin/heparan sulfate with binding affinity for PEDF, which may be important in efficient cell-surface receptor binding. PMID:12625842

  6. JAM-C maintains VEGR2 expression to promote retinal pigment epithelium cell survival under oxidative stress.

    Science.gov (United States)

    Jia, Xin; Zhao, Chen; Chen, Qishan; Du, Yuxiang; Huang, Lijuan; Ye, Zhimin; Ren, Xiangrong; Wang, Shasha; Lee, Chunsik; Tang, Zhongshu; Li, Xuri; Ju, Rong

    2017-04-03

    Junctional adhesion molecule-C (JAM-C) has been shown to play critical roles during development and in immune responses. However, its role in adult eyes under oxidative stress remains poorly understood. Here, we report that JAM-C is abundantly expressed in adult mouse retinae and choroids in vivo and in cultured retinal pigment epithelium (RPE) and photoreceptor cells in vitro. Importantly, both JAM-C expression and its membrane localisation are downregulated by H2O2-induced oxidative stress. Under H2O2-induced oxidative stress, JAM-C is critically required for the survival of human RPE cells. Indeed, loss of JAM-C by siRNA knockdown decreased RPE cell survival. Mechanistically, we show that JAM-C is required to maintain VEGFR2 expression in RPE cells, and VEGFR2 plays an important role in keeping the RPE cells viable since overexpression of VEGFR2 partially restored impaired RPE survival caused by JAM-C knockdown and increased RPE survival. We further show that JAM-C regulates VEGFR2 expression and, in turn, modulates p38 phosphorylation. Together, our data demonstrate that JAM-C plays an important role in maintaining VEGR2 expression to promote RPE cell survival under oxidative stress. Given the vital importance of RPE in the eye, approaches that can modulate JAM-C expression may have therapeutic values in treating diseases with impaired RPE survival.

  7. Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium

    Directory of Open Access Journals (Sweden)

    Patrizia B. Uhl

    2015-01-01

    Full Text Available Retinal pigment epithelium (RPE builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, equine recurrent uveitis (ERU, is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in uveitis.

  8. Photocoagulation of human retinal pigment epithelium in vitro: unravelling the effects on ARPE-19 by transcriptomics and proteomics.

    Science.gov (United States)

    Tababat-Khani, Poya; de la Torre, Carolina; Canals, Francesc; Bennet, Hedvig; Simo, Rafael; Hernandez, Cristina; Fex, Malin; Agardh, Carl-David; Hansson, Ola; Agardh, Elisabet

    2015-06-01

    Despite the extensive use of retinal photocoagulation for ischaemia and vascular leakage in retinal vascular disease, the molecular mechanisms behind its clinical beneficial effects are still poorly understood. One important target of laser irradiation is the retinal pigment epithelium (RPE). In this study, we aimed at identifying the isolated effects of photocoagulation of RPE at both the mRNA and protein expression levels. Human ARPE-19 cells were exposed to photocoagulation. Gene expression and protein expression were compared to untreated cells using microarray and liquid chromatography-mass spectrometry analysis. Genes and proteins queried by microarray and mass spectrometry were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway analyses. Laser irradiation resulted in an induction of the cytoprotective heat-shock protein subfamily Hsp70 as well as in a suppression of the vascular permeability factor carbonic anhydrase 9 (CA9). These expression patterns were evident at both the mRNA and protein levels. KEGG pathway analyses revealed genes and proteins involved in cellular turnover, repair and inflammation. By characterizing the transcriptional and translational effects of laser coagulation on the RPE cells in culture, we have revealed responses, which might contribute to some of the beneficial effects obtained by photocoagulation for ischaemia and vascular leakage in retinal vascular disease. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Pigment epithelium-derived factor: clinical significance in estrogen-dependent tissues and its potential in cancer therapy

    Directory of Open Access Journals (Sweden)

    María Liliana Franco-Chuaire

    2015-09-01

    Full Text Available Pigment epithelium-derived factor (PEDF is a glycoprotein that belongs to the family of non-inhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and anti-metastatic properties. Although the structural domains of the PEDF gene that mediate such diverse effects and their mechanisms of action have not been completely elucidated, there is a large body of evidence describing their diverse range of activities; this evidence combined with the regulation of PEDF expression by sex steroids and their receptors have led to the idea that PEDF is not only a diagnostic and prognostic marker for certain diseases such as cancer, but is also a potential therapeutic target. In this manner, this paper aims to generally review the regulation of PEDF expression and PEDF interactions, as well as the findings that relate PEDF to the role of estrogens and estrogen receptors. In addition, this manuscript will review major advances toward potential therapeutic applications of PEDF.

  10. Correlation Between the Evaluation of Pigmented Lesions by a Multi-spectral Digital Skin Lesion Analysis Device and the Clinical and Histological Features of Melanoma

    OpenAIRE

    Winkelmann, Richard R.; Rigel, Darrell S.; Ferris, Laura; Sober, Arthur; Tucker, Natalie; Cockerell, Clay J.

    2016-01-01

    Objective: To correlate Multi-spectral Digital Skin Lesion Analysis classifier scores with histopathological severity of pigmented lesions and clinical features of melanoma. Design: Classifier scores were computed for 1,632 skin lesions. Dermatologists evaluated the same lesions for Asymmetry, Border Irregularity, Color variegation, Diameter >6mm, Evolution, Patient’s Concern, Regression, and/or “Ugly Duckling” sign. Classifier scores were correlated to the number of clinical risk features an...

  11. Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium.

    Science.gov (United States)

    Chaum, Edward; Winborn, Christina S; Bhattacharya, Sujoy

    2015-06-01

    The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate p53 function in the retina using quantitative trait locus (QTL) analysis. First we examined age-associated changes in the activation and expression levels of p53; known p53 target proteins and markers of innate immune system activation in primary retinal pigment epithelial (RPE) cells that were harvested from young and aged human donors. We observed increased expression of p53, activated caspase-1, CDKN1A, CDKN2A (p16INK4a), TLR4, and IFNα in aged primary RPE cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset ( www.genenetwork.org ) to identify genomic loci that modulate expression of genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL systems biology-based approach. We identified a significant trans-QTL on chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of the genes in this QTL locus are involved in innate immune responses, including Fc receptors, interferon-inducible family genes, and formin 2. Importantly, we found an age-related increase in FCGR3A and FMN2 and a decrease in IFI16 levels in RPE cultures. There is a complex multigenic innate immunity locus that controls expression of genes in the p53 pathway in the RPE, which may play an important role in modulating age-related changes in the retina.

  12. Photodisruption increases the free-radical reactivity of melanosomes isolated from retinal pigment epithelium

    Science.gov (United States)

    Glickman, Randolph D.; Jacques, Steven L.; Schwartz, Jon A.; Rodriguez, Tom; Lam, Kwok-Wai; Buhr, Gwen

    1996-05-01

    Melanin in vivo is usually packaged in melanosomes with protein coats that restrict direct interaction of the melanin with the surrounding medium. We found that disruption of the melanosomes by exposure to a pulsed laser increased the ability of the melanin radicals to oxidize NADPH in a photochemical reaction. Retinal pigment epithelial (RPE) melanosomes were prepared from fresh bovine eyes in 0.25 M sucrose. A reaction mixture of 7 mM NADPH, approximately 7500 RPE melanosomes, and 80 mM Tris buffer, pH 7.2, was prepared in a volume of 60 (mu) l. Of the two 25-(mu) l aliquots taken from this mixture, one was pre-exposed to the 2nd-harmonic output of a Q-switched Nd:YAG laser (532 nm, 1800 10-nsec pulses at 10 Hz), and then was exposed to an Argon ion continuous wave (CW) laser (488.1 and 514.5 nm) for five minutes. The other aliquot was exposed only to the Argon laser. The CW exposure excited the melanin radicals to a reactive state that oxidized NADPH, as assayed by the loss of absorbance at 340 nm. Native melanosomes oxidized less NADPH during Ar+ laser pumping than did melanosomes pre-exposed to the YAG laser. The YAG laser's stimulatory effect on melanosomes reactivity increased as the total energy it delivered rose above 3.5 J (0.14 J/cm2/pulse X 1800 pulses), up to a maximum NADPH oxidation at about 20 J (0.2 J/cm2/pulse X 1800 pulses, beam broadened at higher pulse energy). Electron microscopic analysis of the melanosomes confirmed the progressive physical disruption of melanosomes as the YAG pulse energy increased.

  13. Correlation Between the Evaluation of Pigmented Lesions by a Multi-spectral Digital Skin Lesion Analysis Device and the Clinical and Histological Features of Melanoma.

    Science.gov (United States)

    Winkelmann, Richard R; Rigel, Darrell S; Ferris, Laura; Sober, Arthur; Tucker, Natalie; Cockerell, Clay J

    2016-03-01

    To correlate Multi-spectral Digital Skin Lesion Analysis classifier scores with histopathological severity of pigmented lesions and clinical features of melanoma. Classifier scores were computed for 1,632 skin lesions. Dermatologists evaluated the same lesions for Asymmetry, Border Irregularity, Color variegation, Diameter >6mm, Evolution, Patient's Concern, Regression, and/or "Ugly Duckling" sign. Classifier scores were correlated to the number of clinical risk features and for six histopathological severity levels of pigmented lesions. Average classifier score, Welch's t-test, and chi-square analysis. Melanomas had higher mean classifier scores (3.5) than high-grade dysplastic nevi (2.7, p=0.002), low-grade dysplastic nevi (1.7, pClassifier score and the number of clinical risk characteristics directly correlated (Pearson coefficient 0.32, pclassifier scores to clinical and histological melanoma features supports the effectiveness of Multi-spectral Digital Skin Lesion Analysis in assessing the risk of pigmented lesions requiring biopsy. Optimizing outcomes of dermatologist decisions to biopsy suspicious pigmented lesions may be enhanced utilizing Multi-spectral Digital Skin Lesion Analysis.

  14. DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE.

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    Karen G Shadrach

    Full Text Available BACKGROUND: DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress. METHODOLOGY: Retinal pigment epithelial (RPE cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch's membrane (BM/choroid from AMD eyes. PRINCIPAL FINDINGS: DJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes. CONCLUSIONS/SIGNIFICANCE: DJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative

  15. Morphological changes in the retinal pigment epithelium on spectral-domain OCT in the unaffected eyes with idiopathic central serous chorioretinopathy.

    Science.gov (United States)

    Gupta, Pawan; Gupta, Vishali; Dogra, M R; Singh, Ramandeep; Gupta, Amod

    2010-04-01

    To report the changes seen in the retinal pigment epithelium (RPE) morphology in the asymptomatic eyes of patients with idiopathic central serous chorioretinopathy (ICSC) using spectral-domain Cirrus (TM) high-definition optical coherence tomography (HD-OCT). In a prospective case series, 17 consecutive patients with unilateral ICSC underwent spectral-domain Cirrus (TM) HD-OCT scans for both affected and opposite asymptomatic eye. Three-dimensional single-layer RPE map was studied in both eyes for morphological alterations, and findings were correlated with clinical presentation, fluorescein angiogram, and 5 Line raster scan. Additionally, three-dimensional (3D) single-layer RPE maps done in 111 healthy volunteers served as control. In patients with ICSC, 3D single-layer RPE analysis of asymptomatic eyes showed presence of RPE bumps in 16 (94%) eyes and pigment epithelium detachment (PED) in 2 (11.8%) eyes. The 5 Line raster scan was normal in all eyes. Of 222 normal (control) scans, 18 showed RPE bumps and none showed PED. Conclusions 3D single-layer RPE map showed abnormal pattern in the asymptomatic eyes of patients with unilateral ICSC. Spectral-domain optical coherence tomography showed morphologic alterations in retinal pigment epithelium in both eyes of patients with idiopathic central serous chorioretinopathy.

  16. Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice.

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    Jian Liu

    Full Text Available Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+ cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+ Arg-1(+ myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+ Arg-1(+ phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain.

  17. Ultrasound-mediated microbubble delivery of pigment epithelium-derived factor gene into retina inhibits choroidal neovascularization

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xi-yuan; LIAO Qing; PU Yi-min; TANG Yong-qiang; GONG Xiao; LI Jia; XU Yan; WANG Zhi-gang

    2009-01-01

    Background Many studies have suggested that the imbalance of angiogenic factor and anti-angiogenic factor expression contributes significantly to the development of choroidal neovascularization (CNV), and ultrasound microbubble combination system can increase the gene transfection efficiency successfully. This study was designed to investigate whether ultrasound-mediated microbubble destruction could effectively deliver therapeutic plasmid into the retina of rat, and whether gene transfer of pigment epithelium-derived factor (PEDF) could inhibit CNV.Methods Human retinal pigment epithelial cells were isolated and treated either with ultrasound or plasmid alone, or with a combination of plasmid, ultrasound and microbubbles to approach feasibility of microbubble-enhanced ultrasound enhance PEDFgene expression; For in vivo animal studies, CNV was induced by argon lasgon laser in rats. These rats were randomly assigned to five groups and were treated by infusing microbubbles attached with the naked plasmid DNA of PEDF into the vitreous of rats followed by immediate ultrasound exposure (intravitreal injection); infusing liposomes with the naked plasmid DNA of PEDF into the vitreous (lipofectamine + PEDF); infusing microbubbles attached with PEDF into the orbit of rats with ultrasound irradiation immediately (retrobular injection); infusing microbubbles attached with PEDF into the femoral vein of rats with exposed to ultrasound immediately (vein injection). The CNV rats without any treatment served as control. Rats were sacrificed and eyes were enucleated at 7, 14, and 28 days after treatment. Gene and protein expression of PEDF was detected by quantitative real-time RT-PCR, Western blotting and immunofluorescence staining, respectively. The effect of PEDF gene transfer on CNV was examined by fluorescein fundus angiography.Results In vitro cell experiments showed that microbubbles with ultrasound irradiation could significantly enhance PEDF delivery as compared with

  18. Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients

    Directory of Open Access Journals (Sweden)

    Li X

    2015-03-01

    Full Text Available Xiaoou Li,1–3 Tao Wang,1,2 Ting Yang,1,2 Yongchun Shen,1,2 Jing An,1,2 Lian Liu,1,2 Jiajia Dong,1,2 Lingli Guo,1,2 Diandian Li,1,2 Xue Zhang,1,2 Lei Chen,1,2 Dan Xu,1,2 Fuqiang Wen1,2 1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Rationale: Pigment epithelium-derived factor (PEDF is a 50 kD small secreting glycoprotein that participates in multiple physiological and pathological processes. Recent studies have reported that PEDF plays an important role in inflammatory responses in several diseases. However, the role of PEDF in the pathogenesis of chronic obstructive pulmonary disease (COPD remains unclear.Objective: The aim of the present study is to explore the potential relationship between PEDF and COPD.Methods: We used differential proteomics – stable isotope labeling with amino acids in cell culture – to investigate protein expression profile changes in cigarette smoke extract-treated pulmonary cells and found that the neurotrophic and antiangiogenic protein PEDF was abnormally expressed. Furthermore, Western blotting was used to detect the expression of PEDF in the lung tissue of rats that were exposed to cigarette smoke. Eighty subjects between the ages of 40–90 years, including 20 healthy nonsmokers, ten smoking volunteers, and 50 COPD patients, were recruited from September 2012 until August 2013 in Sichuan Province, People’s Republic of China. We measured the plasma PEDF concentration and classic proinflammatory cytokines by multiplex enzyme-linked immunosorbent assay. In addition, we performed a spirometry examination to

  19. Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat.

    Directory of Open Access Journals (Sweden)

    Amanda-Jayne Carr

    Full Text Available Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs. These induced pluripotent stem (iPS cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD, the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE. As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Long-term visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients.

  20. Pigment epithelium derived factor suppresses expression of Sost/Sclerostin by osteocytes: implication for its role in bone matrix mineralization.

    Science.gov (United States)

    Li, Feng; Song, Na; Tombran-Tink, Joyce; Niyibizi, Christopher

    2015-06-01

    Mutations in Serpinf1 gene which encodes pigment epithelium derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective mineralization. Mechanisms by which PEDF regulates matrix mineralization remain unknown. We examined effect of exogenous PEDF on expression of osteoblastic and osteocytic related genes and proteins in mineralizing osteoblast culture. Mineralizing human osteoblasts supplemented with exogenous PEDF for 14 days deposited 47% more mineral than cells cultured without PEDF. Analysis of selected gene expression by cells in mineralizing cultures supplemented with exogenous PEDF showed reduction in expression of Sclerostin (Sost) by 70%, matrix extracellular phosphoglycoprotein (MEPE) by 75% and dentin matrix protein (DMP-1) by 20% at day 14 of culture. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) expression was not affected. Western blotting and immunoprecipitation showed that sclerostin and MEPE synthesis by osteocytes were reduced by 50% and 60% respectively in mineralizing osteoblasts containing exogenous PEDF. Primary osteocytes exposed to PEDF also reduced synthesis of Sost/sclerostin by 50% within 24 h. For osteoblastic genes, Bone sialoprotein (BSP) was expressed at 75% higher by day 7 in cultures containing exogenous PEDF while Col1A1 expression remained high at all-time points. Total beta-catenin was increased in mineralizing osteoblastic cells suggesting increased Wnt activity. Taken together, the data indicate that PEDF suppressed expression of factors that inhibit mineralization while enhancing those that promote mineralization. The findings also suggest that PEDF may regulate Sost expression by osteocytes leading to enhanced osteoblastic differentiation and increased matrix mineralization.

  1. Increased vascular density and vitreo-retinal membranes accompany vascularization of the pigment epithelium in the dystrophic rat retina.

    Science.gov (United States)

    Caldwell, R B; Roque, R S; Solomon, S W

    1989-09-01

    Observations of vascularization of the retinal pigment epithelium (RPE) and formation of vitreo-retinal membranes (VRMs) in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy suggest that vascular proliferation occurs in this model. To test this hypothesis, we studied the progression of vascular changes in RCS and age-matched control rats using quantitative light microscope morphometry and electron microscopy. At 2 weeks, prior to photoreceptor degeneration, the dystrophic retina is comparable with the control. By 2 months, extensive degeneration of photoreceptor cells results in significant thinning of the dystrophic retina as compared with the control. Signs of vascular degeneration are evident at the electron microscope level--"ghost" vessels consisting of acellular basal lamina surrounded by amorphous electron-dense material; degenerating endothelial cells and pericytes; and abnormal deposits of extracellular matrix (ECM) material around blood vessels. Vascular degeneration is accompanied by glial changes in the form of necrotic perivascular glial processes and abnormal ECM deposits among the altered Muller cell processes. At 2-4 months in the dystrophic retina, numbers of vessel profiles in dystrophic retinas are decreased as compared with controls. However, vascular degeneration is overshadowed by the formation of numerous capillary tufts within the RPE layer, which together with retinal thinning results in increased vessel density. Between 4-12 months, the retinal thickness diminishes further, vascularization of the RPE increases, vitreo-retinal membranes are formed, and vascular density increases. In summary, following an initial period of vascular degeneration, vascularization of the RPE is accompanied by an increase in retinal vessel density and by the formation of vitreo-retinal membranes.

  2. αvβ5 Integrin/FAK/PGC-1α Pathway Confers Protective Effects on Retinal Pigment Epithelium.

    Directory of Open Access Journals (Sweden)

    Murilo F Roggia

    Full Text Available To elucidate the mechanism of the induction of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α by photoreceptor outer segments (POS and its effects on retinal pigment epithelium (RPE.PGC-1α upregulation by POS was confirmed in ARPE-19 cells and in RPE ex vivo. To elucidate the mechanism, siRNAs against β5 integrin, CD36, Mer tyrosine kinase (MerTK, and Atg5, blocking antibodies against CD36 and MerTK, and a specific inhibitor for focal adhesion kinase (FAK were used. We examined the effect of POS-induced PGC-1α upregulation on the levels of reactive oxygen species (ROS, mitochondrial biogenesis, senescence-associated β-galactosidase (SA-β-gal after H2O2 treatment, and lysosomal activity. Lysosomal activity was evaluated through transcriptional factor EB and its target genes, and the activity of cathepsin D. Lipid metabolism after POS treatment was assessed using Oil Red O and BODIPY C11. RPE phenotypes of PGC-1α-deficient mice were examined.POS-induced PGC-1α upregulation was suppressed by siRNA against β5 integrin and a FAK inhibitor. siRNAs and blocking antibodies against CD36 and MerTK enhanced the effect of POS on PGC-1α. The upregulation of PGC-1α increased the levels of mRNA for antioxidant enzymes and stimulated mitochondrial biogenesis, decreased ROS levels, and reduced SA-β-gal staining in H2O2-treated ARPE-19 cells. PGC-1α was critical for lysosomal activity and lipid metabolism after POS treatment. PGC-1α-deficient mice demonstrated an accumulation of type 2 lysosomes in RPE, thickening of Bruch's membrane, and poor choriocapillaris vasculature.The binding, but not the internalization of POS confers protective effects on RPE cells through the αvβ5 integrin/FAK/PGC-1α pathway.

  3. Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

    Science.gov (United States)

    Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

    2013-09-05

    Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Pigment Epithelium-Derived Factor Inhibits Retinal Microvascular Dysfunction Induced By 12/15-Lipoxygenase-Derived Eicosanoids

    Science.gov (United States)

    Ibrahim, Ahmed S.; Tawfik, Amany M.; Hussein, Khaled A; Elshafey, Sally; Markand, Shanu; Rizk, Nasser; Duh, Elia J.; Smith, Sylvia B.; Al-Shabrawey, Mohamed

    2015-01-01

    We recently demonstrated that 12/15-lipoxygenase (LOX) derived metabolites, hydroxyeicosatetraenoic acids (HETEs), contribute to diabetic retinopathy (DR) via NADPH oxidase (NOX) and disruption of the balance in retinal levels of the vascular endothelial growth factor (VEGF) and Pigment Epithelium-Derived Factor (PEDF). Here, we test whether PEDF ameliorates retinal vascular injury induced by HETEs and the underlying mechanisms. Furthermore, we pursue the causal relationship between LOX-NOX system and regulation of PEDF expression during DR. For these purposes, we used an experimental eye model in which normal mice were injected intravitreally with 12/15HETE with/without PEDF. Thereafter, Fluorescein Angiography (FA) was used to evaluate the vascular leakage, followed by Optical coherence tomography (OCT) to assess the presence of angiogenesis. FA and OCT reported an increased vascular leakage and pre-retinal neovascularization, respectively, in response to 12-HETE that were not observed in PEDF-treated group. Moreover, PEDF significantly attenuated the increased levels of vascular cell and intercellular adhesion molecules, VCAM-1 and ICAM-1, elicited by 12-HETE injection. Accordingly, the direct relationship between HETE and PEDF has been explored through in-vitro studies using Müller cells (rMCs) and human retinal endothelial cells (HRECs). The results showed that HETEs triggered the secretion of TNF-α and IL-6, as well as activation of NFκB in rMCs and significantly increased permeability and reduced zonula occludens protein-1 (ZO-1) immunoreactivity in HRECs. All these effects were prevented in PEDF-treated cells. Furthermore, interest in PEDF regulation during DR has been expanded to include NOX system. Retinal PEDF was significantly restored in diabetic mice treated with NOX inhibitor, apocynin, or lacking NOX2 up to 80% of the control level. Collectively, our findings suggest that interfering with LOX-NOX signaling opens up a new direction for treating DR

  5. Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation*

    Science.gov (United States)

    Kunchithapautham, Kannan; Atkinson, Carl; Rohrer, Bärbel

    2014-01-01

    Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. PMID:24711457

  6. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration.

    Science.gov (United States)

    Radu, Roxana A; Hu, Jane; Yuan, Quan; Welch, Darcy L; Makshanoff, Jacob; Lloyd, Marcia; McMullen, Stephen; Travis, Gabriel H; Bok, Dean

    2011-05-27

    Accumulation of vitamin A-derived lipofuscin fluorophores in the retinal pigment epithelium (RPE) is a pathologic feature of recessive Stargardt macular dystrophy, a blinding disease caused by dysfunction or loss of the ABCA4 transporter in rods and cones. Age-related macular degeneration, a prevalent blinding disease of the elderly, is strongly associated with mutations in the genes for complement regulatory proteins (CRP), causing chronic inflammation of the RPE. Here we explore the possible relationship between lipofuscin accumulation and complement activation in vivo. Using the abca4(-/-) mouse model for recessive Stargardt, we investigated the role of lipofuscin fluorophores (A2E-lipofuscin) on oxidative stress and complement activation. We observed higher expression of oxidative-stress genes and elevated products of lipid peroxidation in eyes from abca4(-/-) versus wild-type mice. We also observed higher levels of complement-activation products in abca4(-/-) RPE cells. Unexpectedly, expression of multiple CRPs, which protect cells from attack by the complement system, were lower in abca4(-/-) versus wild-type RPE. To test whether acute exposure of healthy RPE cells to A2E-lipofuscin affects oxidative stress and expression of CRPs, we fed cultured fetal-derived human RPE cells with rod outer segments from wild-type or abca4(-/-) retinas. In contrast to RPE cells in abca4(-/-) mice, human RPE cells exposed to abca4(-/-) rod outer segments adaptively increased expression of both oxidative-stress and CRP genes. These results suggest that A2E accumulation causes oxidative stress, complement activation, and down-regulation of protective CRP in the Stargardt mouse model. Thus, Stargardt disease and age-related macular degeneration may both be caused by chronic inflammation of the RPE.

  7. Autofluorescence of pigmented skin lesions using a pulsed UV laser with synchronized detection: clinical results

    DEFF Research Database (Denmark)

    Cheng, Haynes Pak Hay; Svenmarker, Pontus; Tidemand-Lichtenberg, Peter;

    2010-01-01

    We report preliminary clinical results of autofluorescence imaging of malignant and benign skin lesions, using pulsed 355 nm laser excitation with synchronized detection. The novel synchronized detection system allows high signal-to-noise ratio to be achieved in the resulting autofluorescence...... signal, which may in turn produce high contrast images that improve diagnosis, even in the presence of ambient room light. The synchronized set-up utilizes a compact, diode pumped, pulsed UV laser at 355 nm which is coupled to a CCD camera and a liquid crystal tunable filter. The excitation and image...... capture is sampled at 5 kHz and the resulting autofluorescence is captured with the liquid crystal filter cycling through seven wavelengths between 420 nm and 580 nm. The clinical study targets pigmented skin lesions and evaluates the prospects of using autofluorescence as a possible means...

  8. Pigmented skin lesion detection using random forest and wavelet-based texture

    Science.gov (United States)

    Hu, Ping; Yang, Tie-jun

    2016-10-01

    The incidence of cutaneous malignant melanoma, a disease of worldwide distribution and is the deadliest form of skin cancer, has been rapidly increasing over the last few decades. Because advanced cutaneous melanoma is still incurable, early detection is an important step toward a reduction in mortality. Dermoscopy photographs are commonly used in melanoma diagnosis and can capture detailed features of a lesion. A great variability exists in the visual appearance of pigmented skin lesions. Therefore, in order to minimize the diagnostic errors that result from the difficulty and subjectivity of visual interpretation, an automatic detection approach is required. The objectives of this paper were to propose a hybrid method using random forest and Gabor wavelet transformation to accurately differentiate which part belong to lesion area and the other is not in a dermoscopy photographs and analyze segmentation accuracy. A random forest classifier consisting of a set of decision trees was used for classification. Gabor wavelets transformation are the mathematical model of visual cortical cells of mammalian brain and an image can be decomposed into multiple scales and multiple orientations by using it. The Gabor function has been recognized as a very useful tool in texture analysis, due to its optimal localization properties in both spatial and frequency domain. Texture features based on Gabor wavelets transformation are found by the Gabor filtered image. Experiment results indicate the following: (1) the proposed algorithm based on random forest outperformed the-state-of-the-art in pigmented skin lesions detection (2) and the inclusion of Gabor wavelet transformation based texture features improved segmentation accuracy significantly.

  9. Using 3D differential forms to characterize a pigmented lesion in vivo.

    Science.gov (United States)

    Zhou, Yu; Smith, Melvyn; Smith, Lyndon; Warr, Rob

    2010-02-01

    After the formulation of ABCD rules, many new feature extraction methods are emerging to describe the asymmetry, border irregularity, color variation and diameter of malignant melanoma. In this paper, a new research direction orthogonal to ABCD rules that characterizes 3D local disruption of skin surfaces to realize automatic recognition of melanoma is described. This paper examines 3D differential forms of skin surfaces to characterize the local geometrical properties of melanoma. Firstly, 3D data of skin surfaces are obtained using a photometric stereo device. Then differential forms of lesion surfaces are determined to describe the geometrical texture patterns involved. Using only these geometrical features, a simple least-squared error-based linear classifier can be constructed to realize the classification of malignant melanomas and benign lesions. As with the 3D data of 35 melanoma and 66 benign lesion samples collected from local pigmented lesion clinics, the optimal sensitivity and specificity of the constructed linear classifier are 71.4% and 86.4%, respectively. The total area enclosed by the corresponding receiver operating characteristics curve is 0.823. This study indicates that differential forms obtained from 3D data are very promising in characterizing melanoma. Combining these features with other skin features such as border irregularity and color variation might further improve the accuracy and reliability of the automatic diagnosis of melanoma.

  10. A constitutively active Gαi3 protein corrects the abnormal retinal pigment epithelium phenotype of Oa1-/- mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Young

    Full Text Available PURPOSE: Ocular Albinism type 1 (OA1 is a disease caused by mutations in the OA1 gene and characterized by the presence of macromelanosomes in the retinal pigment epithelium (RPE as well as abnormal crossing of the optic axons at the optic chiasm. We showed in our previous studies in mice that Oa1 activates specifically Gαi3 in its signaling pathway and thus, hypothesized that a constitutively active Gαi3 in the RPE of Oa1-/- mice might keep on the Oa1 signaling cascade and prevent the formation of macromelanosomes. To test this hypothesis, we have generated transgenic mice that carry the constitutively active Gαi3 (Q204L protein in the RPE of Oa1-/- mice and are now reporting the effects that the transgene produced on the Oa1-/- RPE phenotype. METHODS: Transgenic mice carrying RPE-specific expression of the constitutively active Gαi3 (Q204L were generated by injecting fertilized eggs of Oa1-/- females with a lentivirus containing the Gαi3 (Q204L cDNA. PCR, Southern blots, Western blots and confocal microscopy were used to confirm the presence of the transgene in the RPE of positive transgenic mice. Morphometrical analyses were performed using electron microscopy to compare the size and number of melanosomes per RPE area in putative Oa1-/-, Gαi3 (Q204L transgenic mice with those of wild-type NCrl and Oa1-/- mice. RESULTS: We found a correlation between the presence of the constitutively active Gαi3 (Q204L transgene and the rescue of the normal phenotype of RPE melanosomes in Oa1-/-, Gαi3 (Q204L mice. These mice have higher density of melanosomes per RPE area and a larger number of small melanosomes than Oa1-/- mice, and their RPE phenotype is similar to that of wild-type mice. CONCLUSIONS: Our results show that a constitutively active Gαi3 protein can by-pass the lack of Oa1 protein in Oa1-/- mice and consequently rescue the RPE melanosomal phenotype.

  11. Pre-diagnostic digital imaging prediction model to discriminate between malignant melanoma and benign pigmented skin lesion.

    Science.gov (United States)

    Christensen, Jeppe H; Soerensen, Mads B T; Linghui, Zhong; Chen, Sun; Jensen, Morten O

    2010-02-01

    Malignant cutaneous melanoma is the most deadly form of skin cancer with an increasing incidence over the past decades. The final diagnosis provided is typically based on a biopsy of the skin lesion under consideration. To assist the naked-eye examination and decision on whether or not a biopsy is necessary, digital image processing techniques provide promising results. The hypothesis of this study was that a computer-aided assessment tool could assist the evaluation of a pigmented skin lesion. Hence, the overall aim was to discriminate between malignant and benign pigmented skin lesions using digital image processing. Discriminating algorithms utilizing novel well-established morphological operations and methods were constructed. The algorithms were implemented utilizing graphical programming (LabVIEW Vision). Verification was performed with reference to an image database consisting of 97 pigmented skin lesion pictures of various resolutions and light distributions. The outcome of the algorithms was analysed statistically with MATLAB and a prediction model was constructed. The prediction model evaluates pigmented skin lesions with regards to the overall shape, border and colour distribution with a total of nine different discriminating parameters. The prediction model outputs an index score, and by using the optimal threshold value, a diagnostic accuracy of 77% in discriminating between malignant and benign skin lesions was obtained. This is an improvement compared with the naked-eye analysis performed by professionals, rendering the system a significant assistance in detecting malignant cutaneous melanoma.

  12. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

    Science.gov (United States)

    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

  13. Multiphoton absorption is probably not the primary threshold damage mechanism for femtosecond laser pulse exposures in the retinal pigment epithelium

    Science.gov (United States)

    Glickman, Randolph D.; Johnson, Thomas E.

    2004-07-01

    Laser induced breakdown has the lowest energy threshold in the femtosecond domain, and is responsible for production of threshold ocular lesions. It has been proposed that multiphoton absorption may also contribute to ultrashort-pulse tissue damage, based on the observation that 33 fs, 810 nm pulse laser exposures caused more DNA breakage in cultured, primary RPE cells, compared to CW laser exposures delivering the same average power. Subsequent studies, demonstrating two-photon excitation of fluorescence in isolated RPE melanosomes, appeared to support the role of multiphoton absorption, but mainly at suprathreshold irradiance. Additional experiments have not found a consistent difference in the DNA strand breakage produced by ultrashort and CW threshold exposures. DNA damage appears to be dependent on the amount of melanin pigmentation in the cells, rather than the pulsewidth of the laser; current studies have found that, at threshold, CW and ultrashort pulse laser exposures produce almost identical amounts of DNA breakage. A theoretical analysis suggest that the number of photons delivered to the RPE melanosome during a single 33-fsec pulse at the ED50 irradiance is insufficient to produce multiphoton excitation. This result appears to exclude the melanosome as a locus for two- or three-photon excitation; however, a structure with a larger effective absorption cross-section than the melanosome may interact with the laser pulses. One possibility is that the nuclear chromatin acts as a unit absorber of photons resulting in DNA damage, but this does not explain the near equivalence of ultrashort and CW exposures in the comet assay model. This equivalence indicated that multiphoton absorption is not a major contributor to the ultrashort pulse laser damage threshold in the near infrared.

  14. Cistos primários do epitélio pigmentar da íris e corpo ciliar: aspectos de biomicroscopia ultra-sônica Primary cysts of the iris and ciliary body pigment epithelium: ultrasound biomicroscopy features

    Directory of Open Access Journals (Sweden)

    Bernadete Ayres

    2000-10-01

    Full Text Available Objetivo: Descrever as características, incidência e distribuição dos cistos primários de epitélio pigmentar de íris e corpo ciliar ao exame de biomicroscopia ultra-sônica, que devem ser diferenciados de lesões sólidas. Métodos: Foram estudados de modo retrospectivo os prontuários de 73 pacientes, 82 olhos, com diagnóstico ecográfico de cisto primário de íris ou corpo ciliar durante o período de janeiro/97 a dezembro/99. Utilizou-se o biomicroscópio ultra-sônico, aplicando técnicas padronizadas de imersão. Resultados: À biomicroscopia ultra-sônica os cistos caracterizaram-se por apresentarem paredes finas e regulares, e conteúdo anecóico. Quarenta e oito pacientes (65,7% eram do sexo feminino. A maior incidência (28,8% ocorreu para o grupo incluído no intervalo de 20 a 29 anos de idade. Observou-se uma característica distribuição, predominantemente nos quadrantes temporais inferiores. Conclusões: A biomicroscopia ultra-sônica mostrou-se útil no diagnóstico de cistos primários do epitélio pigmentar da íris e do corpo ciliar, auxiliando na diferenciação de patologias tumorais e avaliando possíveis complicações. O conhecimento dos critérios ecográficos e da distribuição epidemiológica facilitam o diagnóstico destas lesões.Purpose: To describe the ultrasound biomicroscopic characteristics, incidence, distribution and location of primary cysts of the iris and ciliary body pigment epithelium, and to differentiate them from solid lesions. Methods: A retrospective study was performed through a review of charts of 73 patients, 82 eyes, with echographic diagnosis of primary cysts of the iris and ciliary body pigment epithelium during a 36-month period (January/97 through December/99. All examinations were performed using an ultrasound biomicroscope applying standard immersion techniques. Results: Ultrasound biomicroscopy revealed typical findings of the primary cysts of the pigment epithelium such as thin

  15. Combined Hamartoma of the Retina and Retinal Pigment Epithelium in a Patient with Gorlin Syndrome: Spontaneous Partial Resolution of Traction Caused by Epiretinal Membrane

    Science.gov (United States)

    Sánchez-Vicente, José L.; Rueda, Trinidad; Rodríguez de la Rúa-Franch, Enrique; Molina-Socola, Fredy E.; Vital-Berral, Cristina; Alfaro-Juárez, Asunción; López-Herrero, Fernando; Muñoz-Morales, Ana

    2016-01-01

    Purpose. To describe the case of spontaneous resolution of epiretinal membrane in a patient with Combined Hamartoma of the Retina and Retinal Pigment Epithelium (CHR-RPE), in the clinical context of Gorlin Syndrome (GS). Methods. Observational case report of a 12-year-old female patient is presented. The diagnosis of CHRRPE was made by OCT and fundus examination, which showed a mound of disorganized tissue originating from retina and retinal pigment epithelium. Epiretinal membrane (EM) was also detected. Genetic study was performed to confirm the diagnosis of GS. Results. The patient was observed for 39 months, showing spontaneous resolution of the traction caused by the EM and improvement in visual acuity (VA), which was 20/80 at initial presentation, rising to 20/40 after follow-up period. Conclusions. The presence of EM in CHR-REP is a cause of reduction of visual acuity. Management of this condition is controversial; however, we would like to highlight that spontaneous resolution of the traction caused by EM is possible, resulting in recovery of VA. PMID:27595027

  16. Histological and electrophysiological changes in the retinal pigment epithelium after injection of sodium iodate in the orbital venus plexus of pigmented rats

    Directory of Open Access Journals (Sweden)

    Hamid Aboutaleb Kadkhodaeian

    2016-01-01

    Conclusion: NaIO3injection into the retrobulbar venous plexus of pigmented rats can result in significant and progressive damage to the RPE and subsequently to the neuroretina of the injected eye, and may serve as a model of retinal degeneration.

  17. In vivo characterization of human pigmented lesions by degree of linear polarization image maps using incident linearly polarized light.

    Science.gov (United States)

    Kim, Jihoon; John, Raheel; Wu, Paul J; Martini, Mary C; Walsh, Joseph T

    2010-01-01

    Melanoma is the most serious form of skin cancer and often appears as an evolving multicolored skin growth. It is well documented that pre-existing atypical or dysplastic nevi can evolve into a melanoma. The development of an in vivo imaging system to characterize benign and malignant nevi has been emphasized to aid in early detection of melanoma. The goal of this study is to utilize a novel Stokes polarimetry imaging (SPI) system for the characterization of pigmented lesions, and to evaluate the SPI system in comparison to dermoscopy and histology images. Linearly polarized light with varying incident polarization angles (IPA) illuminated various types of pigmented lesions. The melanocytic nesting patterns of pigmented lesions were characterized by constructing the degree-of-linear-polarization (DOLP) image map with comparison to dermoscopy and histology. The incident polarized light was filtered by visible filters for spectral imaging and incident deeply penetrating red light was used to correlate the SPI image with histopathological examination. The DOLP images with varying IPA at different visible wavelengths were used to characterize various kinds of pigmented lesions by showing subsurface melanocytic nesting distribution as well as morphological information with better resolution and contrast. In correlation with dermoscopy and histology, various defining features such as compound, junctional, lentiginous, reticular, globular patterns of melanocytic nests were identified. When imaging pigmented melanocytic lesions, the SPI system with varying IPA at the red light wavelength can better define the melanocytic nesting patterns in both the dermal epidermal junction and the dermis. The SPI system has the potential to be an effective in vivo method of detecting pre-malignant nevi and melanoma.

  18. Inter- and intra-variability of pigmented skin lesions: could the ABCD rule be influenced by host characteristics?

    Science.gov (United States)

    Burroni, Marco; Dell'Eva, Giordana; Corona, Rosamaria; Sera, Francesco; Bono, Riccardo; Sbano, Paolo; Andreassi, Lucio; Rubegni, Pietro

    2004-08-01

    Many differences in color, shape and dimension exist between different moles even in the same individual. Major differences might be accounted for anatomical location, genetic factors and by environmental factors, mainly sunlight exposure. Therefore, it would be of great value, when evaluating skin lesions, to take into account the degree of intra- and inter-variability of several diagnostic parameters. In order to assess the morphologic and chromatic differences between lesions belonging to different patients and between lesions belonging to the same individual, we examined objective digital parameters obtained with dermatoscopic analysis, using the DBDermo MIPS system (BIO MIPS Engineering, S.R.L, siena, Italy). The automatic classifier inside the software is based on a 'match by similarity' algorithm, based on the measurement of the Euclidean distances of all variables considered from the reference image. Two-hundred and four clinically benign pigmented lesion, belonging to 18 patients were examined, stored and automatically processed. For each lesion objective parameters related to geometry, color and texture were automatically evaluated. We found skin color (healthy skin) is objectively different from subject to subject and the lesion color is more similar among different lesions of the same patient than among lesions belonging to different individuals both in their darkest and slightly dark component. We also observed that lesion dimensions are individual correlates, i.e. the probability for a lesion to be large is higher when the other, in the same patient, is large. Many parameters of pigmented skin lesions evaluated by digital dermoscopy analysis are similar in the same patient and different from those belonging to different individuals. This indicates that, when considering a lesion, we should take into account the peculiar patient's characteristics.

  19. Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity

    DEFF Research Database (Denmark)

    Corydon, Thomas J; Mann, Vivek; Slumstrup, Lasse;

    2016-01-01

    BACKGROUND/AIMS: Microgravity (µg) has adverse effects on the eye of humans in space. The risk of visual impairment is therefore one of the leading health concerns for NASA. The impact of µg on human adult retinal epithelium (ARPE-19) cells is unknown. METHODS: In this study we investigated the i...

  20. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography

    DEFF Research Database (Denmark)

    Nagiel, Aaron; Freund, K Bailey; Spaide, Richard F;

    2013-01-01

    PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT......). DESIGN: Retrospective observational case series. METHODS: OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur...... to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution...

  1. Role of wide-field autofluorescence imaging and scanning laser ophthalmoscopy in differentiation of choroidal pigmented lesions

    Institute of Scientific and Technical Information of China (English)

    Lukas; Reznicek; Carmen; Stumpf; Florian; Seidensticker; Anselm; Kampik; Aljoscha; S; Neubauer; Marcus; Kernt

    2014-01-01

    ·AIM:Toevaluatethe diagnostic properties of wide-field fundus autofluorescence(FAF) scanning laser ophthalmoscope(SLO) imaging for differentiating choroidal pigmented lesions.·METHODS: A consecutive series of 139 patients were included, 101 had established choroidal melanoma with13 untreated lesions and 98 treated with radiotherapy.Thirty-eight had choroidal nevi. All patients underwent a full ophthalmological examination, undilated wide-field imaging, FAF and standardized US examination. FAF images and imaging characteristics from SLO were correlated with the structural findings in the two patient groups.·RESULTS: Mean FAF intensity of melanomas was significantly lower than the FAF of choroidal nevi. Only 1out of 38 included eyes with nevi touched the optic disc compared to 31 out of 101 eyes with melanomas. In 18 out of 101 melanomas subretinal fluid was seen at the pigmented lesion compared to none seen in eyes with confirmed choroidal nevi. In "green laser separation", a trend towards more mixed FAF appearance of melanomas compared to nevi was observed. The mean maximal and minimal transverse and longitudinal diameters of melanomas were significantly higher than those of nevi.·CONCLUSION: Wide-field SLO and FAF imaging may be an appropriate non-invasive diagnostic screening tool to differentiate benign from malign pigmented choroidal lesions.

  2. Understanding visual search patterns of dermatologists assessing pigmented skin lesions before and after online training.

    Science.gov (United States)

    Krupinski, Elizabeth A; Chao, Joseph; Hofmann-Wellenhof, Rainer; Morrison, Lynne; Curiel-Lewandrowski, Clara

    2014-12-01

    The goal of this investigation was to explore the feasibility of characterizing the visual search characteristics of dermatologists evaluating images corresponding to single pigmented skin lesions (PSLs) (close-ups and dermoscopy) as a venue to improve training programs for dermoscopy. Two Board-certified dermatologists and two dermatology residents participated in a phased study. In phase I, they viewed a series of 20 PSL cases ranging from benign nevi to melanoma. The close-up and dermoscopy images of the PSL were evaluated sequentially and rated individually as benign or malignant, while eye position was recorded. Subsequently, the participating subjects completed an online dermoscopy training module that included a pre- and post-test assessing their dermoscopy skills (phase 2). Three months later, the subjects repeated their assessment on the 20 PSLs presented during phase I of the study. Significant differences in viewing time and eye-position parameters were observed as a function of level of expertise. Dermatologists overall have more efficient search than residents generating fewer fixations with shorter dwells. Fixations and dwells associated with decisions changing from benign to malignant or vice versa from photo to dermatoscopic viewing were longer than any other decision, indicating increased visual processing for those decisions. These differences in visual search may have implications for developing tools to teach dermatologists and residents about how to better utilize dermoscopy in clinical practice.

  3. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2010-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  4. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    LENUS (Irish Health Repository)

    Field, S

    2012-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  5. Human Bone Marrow Stromal Cells can Differentiate to a Retinal Pigment Epithelial Phenotype when Co-Cultured with Pig Retinal Pigment Epithelium using a Transwell System

    Directory of Open Access Journals (Sweden)

    Ping Duan

    2013-05-01

    Full Text Available Background: There is an increasing interest in generating retinal pigment epithelial (RPE cells from stem cells for therapy against degenerative eye diseases. Human bone marrow stromal cells (hBMSCs can be induced to express retinal neuron-specific markers when co-cultured with retinal neurons, however, whether hBMSCs can differentiate into RPE-like cells in a co-culture system has not been clarified. Methods: The induction of hBMSCs into RPE-like cells was performed by combining hBMSCs and pig RPE cells in a transwell system. The biomarkers of hBMSCs-derived RPE cells were determined by quantitative RT-PCR and immunofluorescence. The function of induced cells was assayed by ELISA for secretion of neurotrophic factors. Results: Intracellular pigment granules and many RPE markers existed in hBMSCs-derived RPE cells after co-culturing with pig RPE cells for 14 days. Typical RPE functions, such as phagocytosis of photoreceptor outer segments and secretion of the trophic factors, brain-derived neurotrophic factor (BDNF and glia-derived neurotrophic factor (GDNF, were observed in these induced cells. Conclusion: hBMSCs can be induced toward functional RPE cells simply by transwell-based co-culture with RPE cells.

  6. Benzo(a)pyrene and X-rays induce reversions of the pink-eyed unstable mutation in the retinal pigment epithelium of mice.

    Science.gov (United States)

    Bishop, A J; Kosaras, B; Sidman, R L; Schiestl, R H

    2000-12-20

    The pink-eyed unstable (p(un)) mutation is the result of a 70kb tandem duplication within the murine p gene. Homologous deletion/recombination of the locus to wild-type occurs spontaneously in embryos and results in pigmented spots in the fur and eye that persist for life. Such deletion events are also inducible by a variety of DNA damaging agents, as we have observed previously with the fur spot assay. Here, we describe the use of the retinal pigment epithelium (RPE) of the eye to detect reversion events induced with two differently acting agents. Benzo(a)pyrene (B(a)P) induces a high frequency, and X-ray exposure a more modest increase, of p(un) reversion in both the fur and the eye. The eye-spot assay requires fewer mice for significant results than the fur spot assay. Previous work had elucidated the cell proliferation pattern in the RPE and a position effect variegation phenotype in the pattern of p(un) reversions, which we have confirmed. Acute exposure to B(a)P or X-rays resulted in an increased frequency of reversion events. The majority of the spontaneous reversions lie toward the periphery of the RPE whereas induced events are found more centrally, closer to the optic nerve head. The induced distribution corresponds to the major sites of cell proliferation in the RPE at the time of exposure, and further advocates the proposal that dividing cells are at highest risk to develop deletions.

  7. Oral melanoacanthoma: A rare case of diffuse oral pigmentation

    Directory of Open Access Journals (Sweden)

    Anish Ashok Gupta

    2012-01-01

    Full Text Available The clinical presentation of diffuse pigmentation can be alarming to the patient as well as the clinician. A histopathologic examination of a pigmented lesion is necessary in most of the cases in the oral cavity. Oral melanoacanthoma is a very rare diffuse pigmentation with no specific treatment required. It shows increased number of dendritic melanocytes in an acanthotic epithelium. We present a rare case of diffuse pigmentation in the oral cavity whose diagnosis was done on the basis of clinical presentation and histopathology. Also immunohistochemistry was done.

  8. Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis.

    Science.gov (United States)

    Carrión, Daniela Calderón; Korkmaz, Yüksel; Cho, Britta; Kopp, Marion; Bloch, Wilhelm; Addicks, Klaus; Niedermeier, Wilhelm

    2016-03-30

    The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  9. Comparison of the Distribution of Morphological Disorganization of Pigmented Lesions in a Community-based Practice versus a University-based Clinical Setting as Measured by a Multispectral Digital Skin Lesion Analysis Device: Impact on Diagnosis.

    Science.gov (United States)

    Winkelmann, Richard R; Nikolaidis, Gregory; Rigel, Darrell S; Tucker, Natalie; Speck, Laura

    2015-02-01

    To observe how a multispectral digital skin lesion analysis device was used by dermatologists in a community-based clinical setting and determine differences from a university-based environment. Use of multispectral digital skin lesion analysis was incorporated into a community-based practice by 12 dermatologists across six clinics over seven consecutive days with the data provided by the device integrated as an adjuvant to their clinical evaluation for their pigmented lesion management decisions. Multispectral digital skin lesion analysis results were collected electronically for lesions prior to biopsy, and histopathological evaluation was performed for the biopsied lesions. Multispectral digital skin lesion analysis and pathology results were then compared to assess the degree of morphological disorganization. Study of 160 consecutive patients in community-based clinical setting. Proportion of "low" and "high" disorganization lesions identified by multispectral digital skin lesion analysis. Of the 344 pigmented skin lesions analyzed by multispectral digital skin lesion analysis, 255 were high disorganization, 113 of which were biopsied. Of the 89 lesions evaluated by multispectral digital skin lesion analysis to be low disorganization, seven were biopsied and all pathology was benign. Data demonstrate a higher rate of multispectral digital skin lesion analysis low disorganization readings for pigmented skin lesions (32% for single use per patient lesions, plesions, plesions clinics providing data for the university-based clinical study (10%). Multispectral digital skin lesion analysis in the community-based clinical setting may outperform specificity results from the university-based clinical trial study, perhaps because of a higher proportion of subtle lesions encountered at high-risk pigmented lesion clinics of participating major academic centers as compared with those in a community-based practice setting.

  10. 线粒体DNA损伤与视网膜色素上皮细胞关系的研究进展%The relationship between mitochondrial DNA damage and retinal pigment epithelium cells

    Institute of Scientific and Technical Information of China (English)

    俞永珍; 邹秀兰; 邹玉平

    2015-01-01

    Mitochondrial DNA (mtDNA) is a genetic effect DNA molecule of double closed loop, and is crucial for cells and their functions. Mitochondria take an active part in physiological activities of retinal pigment epithelium (RPE) cells. The oxidative stress is usually occurred in RPE for its active metabolism, which can lead to mitochondria and mtDNA dam⁃age. Once mitochondria and mtDNA lesions have not been repaired timely, the lesions can be accumulated, which can cause dysfunctions and damaged-structures of RPE and mitochondria, and can motivate the progression of cell apoptosis. In the end it can result in some ocular related diseases such as aged-related macular degeneration (AMD). This study reviewed the functional relationship between mtDNA and RPE, and repair and detection methods of mtDNA damage.%线粒体DNA(mtDNA)是线粒体内具有遗传效应的双股闭环DNA分子,对细胞及其功能具有重要作用。视网膜色素上皮(RPE)细胞活动亦由大量线粒体参与。因RPE细胞代谢活跃,当发生氧化应激时可引起线粒体及mtDNA损伤;当线粒体及mtDNA损伤无法及时修复而使损伤积累,可引起RPE及线粒体功能障碍,并诱发启动细胞凋亡,进而引发某些眼病,如年龄相关性黄斑变性等。现就mtDNA与RPE细胞的功能关系、mtDNA损伤修复及检测方法作一综述。

  11. Spectrophotometric intracutaneous analysis versus dermoscopy for the diagnosis of pigmented skin lesions: prospective, double-blind study in a secondary reference centre

    DEFF Research Database (Denmark)

    Glud, Martin; Gniadecki, Robert; Drzewiecki, Krzysztof T

    2009-01-01

    Dermoscopy is considered to be the golden standard for the clinical assessment of pigmented skin lesions. In expert hands, this instrument improves both sensitivity and specificity for the diagnosis of melanoma, however, the outcome is highly dependent on the skills and experience of the examiner....... Spectrophotometric intracutaneous analysis (SIAscopy) is a new, commercially available method of analyzing pigmented skin lesions noninvasively. The diagnosis is based on objective features such as the presence of dermal pigment, vascularity of the lesion, and the integrity of collagen. The objective of this study...... investigated by dermoscopy and SIAscopy and subsequently excised. Histopathologically, 12 lesions were diagnosed as malignant melanoma. Both dermoscopy and SIAscopy overestimated the proportion of possible malignant lesions (n=24 and 41, respectively) and had sensitivities of 92 and 100%, respectively...

  12. Loss of Ab-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

    Institute of Scientific and Technical Information of China (English)

    Daniela Caldero n Carrio n; Yu ksel Korkmaz; Britta Cho; Marion Kopp; Wilhelm Bloch; Klaus Addicks; Wilhelm Niedermeier

    2016-01-01

    The Merkel cell-neurite complex initiates the perception of touch and mediates Ab slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Ab- and Ad-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oralmucosa epitheliumof lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Ab-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis.

  13. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue

    Directory of Open Access Journals (Sweden)

    Richard J. Davis

    2017-07-01

    Full Text Available Age-related macular degeneration (AMD is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC-derived RPE cells (RPESC-RPE preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

  14. From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium.

    Science.gov (United States)

    Reichman, Sacha; Terray, Angélique; Slembrouck, Amélie; Nanteau, Céline; Orieux, Gaël; Habeler, Walter; Nandrot, Emeline F; Sahel, José-Alain; Monville, Christelle; Goureau, Olivier

    2014-06-10

    Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease.

  15. Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity

    Directory of Open Access Journals (Sweden)

    Thomas J. Corydon

    2016-11-01

    Full Text Available Background/Aims: Microgravity (µg has adverse effects on the eye of humans in space. The risk of visual impairment is therefore one of the leading health concerns for NASA. The impact of µg on human adult retinal epithelium (ARPE-19 cells is unknown. Methods: In this study we investigated the influence of simulated µg (s-µg; 5 and 10 days (d, using a Random Positioning Machine (RPM, on ARPE-19 cells. We performed phase-contrast/fluorescent microscopy, qRT-PCR, Western blotting and pathway analysis. Results: Following RPM-exposure a subset of ARPE-19 cells formed multicellular spheroids (MCS, whereas the majority of the cells remained adherent (AD. After 5d, alterations of F-actin and fibronectin were observed which reverted after 10d-exposure, suggesting a time-dependent adaptation to s-µg. Gene expression analysis of 12 genes involved in cell structure, shape, adhesion, migration, and angiogenesis suggested significant changes after a 10d-RPM-exposure. 11 genes were down-regulated in AD and MCS 10d-RPM-samples compared to 1g, whereas FLK1 was up-regulated in 5d- and 10d-RPM-MCS-samples. Similarly, TIMP1 was up-regulated in 5d-RPM-samples, whereas the remaining genes were down-regulated in 5d-RPM-samples. Western blotting revealed similar changes in VEGF, β-actin, laminin and fibronectin of 5d-RPM-samples compared to 10d, whereas different alterations of β-tubulin and vimentin were observed. The pathway analysis showed complementing effects of VEGF and integrin β-1. Conclusions: These findings clearly show that s-µg induces significant alterations in the F-actin-cytoskeleton and cytoskeleton-related proteins of ARPE-19, in addition to changes in cell growth behavior and gene expression patterns involved in cell structure, growth, shape, migration, adhesion and angiogenesis.

  16. Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung-Jin [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Yun, Jang-Hyuk; Heo, Jong-Ik [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Lee, Eun Hui [Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Min, Hye Sook [Department of Pathology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Choi, Tae Hyun, E-mail: psthchoi@snu.ac.kr [Department of Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Department of Pediatric Plastic and Reconstructive Surgery, Seoul National University Children’s Hospital, Seoul 110-744 (Korea, Republic of); Cho, Chung-Hyun, E-mail: iamhyun@snu.ac.kr [Department of Pharmacology, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Department of Biomedical Science, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Ischemic/Hypoxic Disease Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of); Cancer Research Institute, College of Medicine, Seoul National University, Seoul 110-799 (Korea, Republic of)

    2014-11-14

    Highlights: • PEDF was expressed and induced during the involuting phase of IH. • PEDF inhibited the cell growth of the involuting HemECs in an autocrine manner. • PEDF suppression restored the impaired cell growth of the involuting HemECs. - Abstract: Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.

  17. Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro

    Institute of Scientific and Technical Information of China (English)

    WANG Feng-hua; SUN Xiao-dong; ZHANG Xi; XU Xun; ZHU Qi; HUANG Jian-nan; FAN Ying; GU Qing; LIU Hai-yang

    2007-01-01

    Background Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.Methods Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.Results Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However,the concentration of PEDF which we used has little effect on normal CECs.Conclusions PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell.These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.

  18. Proof of concept for AAV2/5-mediated gene therapy in iPSC-derived retinal pigment epithelium of a choroideremia patient.

    Science.gov (United States)

    Cereso, Nicolas; Pequignot, Marie O; Robert, Lorenne; Becker, Fabienne; De Luca, Valerie; Nabholz, Nicolas; Rigau, Valerie; De Vos, John; Hamel, Christian P; Kalatzis, Vasiliki

    2014-01-01

    Inherited retinal dystrophies (IRDs) comprise a large group of genetically and clinically heterogeneous diseases that lead to progressive vision loss, for which a paucity of disease-mimicking animal models renders preclinical studies difficult. We sought to develop pertinent human cellular IRD models, beginning with choroideremia, caused by mutations in the CHM gene encoding Rab escort protein 1 (REP1). We reprogrammed REP1-deficient fibroblasts from a CHM (-/y) patient into induced pluripotent stem cells (iPSCs), which we differentiated into retinal pigment epithelium (RPE). This iPSC-derived RPE is a polarized monolayer with a classic morphology, expresses characteristic markers, is functional for fluid transport and phagocytosis, and mimics the biochemical phenotype of patients. We assayed a panel of adeno-associated virus (AAV) vector serotypes and showed that AAV2/5 is the most efficient at transducing the iPSC-derived RPE and that CHM gene transfer normalizes the biochemical phenotype. The high, and unmatched, in vitro transduction efficiency is likely aided by phagocytosis and mimics the scenario that an AAV vector encounters in vivo in the subretinal space. We demonstrate the superiority of AAV2/5 in the human RPE and address the potential of patient iPSC-derived RPE to provide a proof-of-concept model for gene replacement in the absence of an appropriate animal model.

  19. Inhibition by miR-410 facilitates direct retinal pigment epithelium differentiation of umbilical cord blood-derived mesenchymal stem cells

    Science.gov (United States)

    Choi, Soon Won; Kim, Jae-Jun; Seo, Min-Soo; Park, Sang-Bum; Shin, Tae-Hoon; Shin, Ji-Hee; Seo, Yoojin; Kim, Hyung-Sik

    2017-01-01

    Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction. PMID:27297412

  20. Comparison of Progression Rate of Retinal Pigment Epithelium Loss in Patients with Neovascular Age-Related Macular Degeneration Treated with Ranibizumab and Aflibercept

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    Juliana Wons

    2017-01-01

    Full Text Available Purpose. Retinal pigment epithelium (RPE loss in neovascular age-related macular degeneration (nAMD seem to have a linear progression but might be influenced by the treatment. The purpose of the study is the comparison of RPE loss over three years in patients treated with intravitreal ranibizumab to patients who were switched to aflibercept. Methods. A retrospective analysis with 96 eyes switched to aflibercept was conducted. The progression rate of RPE loss was evaluated in patients who showed atrophy one year prior to switch (n=17 or on switch date (n=19. The RPE loss was evaluated by spectral domain optical coherence tomography (SD-OCT. Further, 22 eyes from patients treated with ranibizumab were compared. Results. The median yearly progression of RPE loss after square root transformation showed no significant difference in the year prior to switch compared to the year after switch (p=0.854. In patients who received only ranibizumab, the median yearly progression of RPE loss was 0.15 mm/y, for aflibercept patients, 0.13 mm/y. This difference was not statistically significant (p=0.172. Conclusions. There seems to be a linear progression rate of RPE loss in patients treated with ranibizumab as well as in patients with aflibercept. No significant increase of progression rate was found after switch to aflibercept.

  1. Adenoviral E4 Gene Stimulates Secretion of Pigmental Epithelium Derived Factor (PEDF) that Maintains Long-term Survival of Human Glomerulus-derived Endothelial Cells*

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    Jerebtsova, Marina; Kumari, Namita; Obuhkov, Yuri; Nekhai, Sergei

    2012-01-01

    Renal glomerular endothelial cells are specialized cells with an important role in physiological filtration and glomerular disease. However, maintenance of human primary endothelial cells requires stimulation with serum and growth factors that often results in modification of the cells properties. Previously, expression of early adenovirus region E4 was shown to help maintaining long-term survival of human endothelial cells in serum free media without addition of growth factors. In the current study, we showed that media conditioned with human epithelial cells stably transfected with Ad E4 region also supported survival of human glomerulus-derived endothelial cells in serum-free media. Mass-spectrometry analysis of the conditioned media identified pigmental epithelium derived factor (PEDF) as a major component of the conditioned media. PEDF expression in 293-E4 cells was validated by RT-PCR, Western blot and ELISA analysis. PEDF expression was detected in mouse glomeruli. Supplementation with recombinant PEDF supported survival of primary endothelial cells and the cells transformed with SV40 large T antigen in serum-free media, and extended the life-span of both cell cultures. PEDF did not inhibit FGF-2 stimulated growth and tubulogenesis of endothelial cells. Thus we demonstrated that adenoviral E4 region stimulated expression and secretion of PEDF by human renal epithelial cells that acted as a survival factor for glomerulus-derived endothelial cells. PMID:22915824

  2. Oxalomalate reduces expression and secretion of vascular endothelial growth factor in the retinal pigment epithelium and inhibits angiogenesis: Implications for age-related macular degeneration

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    Sung Hwan Kim

    2016-12-01

    Full Text Available Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF, secreted by the retinal pigment epithelium (RPE, in pathological angiogenesis and the development of choroidal neovascularization (CNV in age-related macular degeneration (AMD. RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects. Oxalomalate (OMA is a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase (IDH, which plays an important role in cellular signaling pathways regulated by reactive oxygen species (ROS. Here, we have investigated the inhibitory effect of OMA on the expression of VEGF, and the associated underlying mechanism of action, using in vitro and in vivo RPE cell models of AMD. We found that OMA reduced the expression and secretion of VEGF in RPE cells, and consequently inhibited CNV formation. This function of OMA was linked to its capacity to activate the pVHL-mediated HIF-1α degradation in these cells, partly via a ROS-dependent ATM signaling axis, through inhibition of IDH enzymes. These findings reveal a novel role for OMA in inhibiting RPE-derived VEGF expression and angiogenesis, and suggest unique therapeutic strategies for treating pathological angiogenesis and AMD development.

  3. MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors.

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    Shelby, Shameka J; Feathers, Kecia L; Ganios, Anna M; Jia, Lin; Miller, Jason M; Thompson, Debra A

    2015-11-01

    Photoreceptor outer segments (OS) in the vertebrate retina undergo a process of continual renewal involving shedding of disc membranes that are cleared by phagocytic uptake into the retinal pigment epithelium (RPE). In dystrophic Royal College of Surgeons (RCS) rats, OS phagocytosis is blocked by a mutation in the gene encoding the receptor tyrosine kinase MERTK. To identify proteins tyrosine-phosphorylated downstream of MERTK in the RPE, MALDI-mass spectrometry with peptide-mass fingerprinting was used in comparative studies of RCS congenic and dystrophic rats. At times corresponding to peak phagocytic activity, the RAB GTPase effector GDP dissociation inhibitor alpha (GDI1) was found to undergo tyrosine phosphorylation only in congenic rats. In cryosections of native RPE/choroid, GDI1 colocalized with MERTK and the intracellular tyrosine-kinase SRC. In cultured RPE-J cells, and in transfected heterologous cells, MERTK stimulated SRC-mediated tyrosine phosphorylation of GDI1. In OS-fed RPE-J cells, GDI1 colocalized with MERTK and SRC on apparent phagosomes located near the apical membrane. In addition, both GDI1 and RAB5, a regulator of vesicular transport, colocalized with ingested OS. Taken together, these findings identify a novel role of MERTK signaling in membrane trafficking in the RPE that is likely to subserve mechanisms of phagosome formation.

  4. Positive association of circulating levels of advanced glycation end products (AGEs) with pigment epithelium-derived factor (PEDF) in a general population.

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    Yamagishi, Sho-Ichi; Matsui, Takanori; Adachi, Hisashi; Takeuchi, Masayoshi

    2010-02-01

    We have recently found that serum levels of pigment epithelium-derived factor (PEDF), a glycoprotein with anti-oxidative and anti-inflammatory properties, are elevated in proportion to the accumulation of the number of the components of the metabolic syndrome. Since formation and accumulation of advanced glycation end products (AGEs) progress under the metabolic syndrome and that PEDF could inhibit the AGE-elicited tissue damage, it is conceivable that PEDF levels may be increased as a counter-system against AGEs in patients with the metabolic syndrome. However, correlation between circulating levels of AGEs and PEDF in humans remains to be elucidated. In this study, we investigated the relationship between serum AGE and PEDF levels in a general population and examined the effects of AGEs on PEDF gene expression in vitro. One hundred ninety-six Japanese subjects in a general population underwent a complete history and physical examination, determination of blood chemistries, including serum levels of AGEs and PEDF. In multiple regression analyses, creatinine, body mass index, triglycerides, AGEs and insulin were independently correlated with serum PEDF levels. AGEs dose-dependently increased PEDF gene expression in cultured adipocytes and liver cells. Our present study demonstrated first that circulating AGEs were one of the independent correlates of serum levels of PEDF. Adipose tissue and liver may be target organs for the AGE-induced PEDF overexpression in humans. Serum PEDF levels may be elevated in response to circulating AGEs as a counter-system against the AGE-elicited tissue damage.

  5. Neurotrophic Effect of Adipose Tissue-Derived Stem Cells on Erectile Function Recovery by Pigment Epithelium-Derived Factor Secretion in a Rat Model of Cavernous Nerve Injury

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    Xin Chen

    2016-01-01

    Full Text Available The paracrine effect is the major mechanism of stem cell therapy. However, the details of the effect’s mechanism remain unknown. The aim of this study is to investigate whether adipose tissue-derived stem cells (ADSCs can ameliorate cavernous nerve injury-induced erectile dysfunction (CNIED rats and to determine its mechanism. Twenty-eight days after intracavernous injection of 5-ethynyl-2-deoxyuridine- (EdU- labeled ADSCs, the erectile function of all the rats was evaluated by intracavernosal pressure (ICP. The ADSCs steadily secreted detectable pigment epithelium-derived factor (PEDF in vitro. The expression of PEDF increased in the penis of the bilateral cavernous nerve injury (BCNI group for 14 days and then gradually decreased. On day 28 after the intracavernous injection, the ADSCs group exhibited a significantly increased ICP compared with the phosphate buffered saline- (PBS- treated group. Moreover, the neuronal nitric oxide synthase (nNOS and S100 expression in penile dorsal nerves and the smooth muscle content to collagen ratio in penile tissues significantly increased. Furthermore, elevated PEDF, p-Akt, and p-eNOS were identified in the ADSCs group. This study demonstrated that intracavernous injection of ADSCs improved erectile function, repaired the nerve, and corrected penile fibrosis. One potential mechanism is the PEDF secretion of ADSCs and subsequent PI3K/Akt pathway activation.

  6. GABA maintains the proliferation of progenitors in the developing chick ciliary marginal zone and non-pigmented ciliary epithelium.

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    Henrik Ring

    Full Text Available GABA is more than the main inhibitory neurotransmitter found in the adult CNS. Several studies have shown that GABA regulates the proliferation of progenitor and stem cells. This work examined the effects of the GABA(A receptor system on the proliferation of retinal progenitors and non-pigmented ciliary epithelial (NPE cells. qRT-PCR and whole-cell patch-clamp electrophysiology were used to characterize the GABA(A receptor system. To quantify the effects on proliferation by GABA(A receptor agonists and antagonists, incorporation of thymidine analogues was used. The results showed that the NPE cells express functional extrasynaptic GABA(A receptors with tonic properties and that low concentration of GABA is required for a baseline level of proliferation. Antagonists of the GABA(A receptors decreased the proliferation of dissociated E12 NPE cells. Bicuculline also had effects on progenitor cell proliferation in intact E8 and E12 developing retina. The NPE cells had low levels of the Cl-transporter KCC2 compared to the mature retina, suggesting a depolarising role for the GABA(A receptors. Treatment with KCl, which is known to depolarise membranes, prevented some of the decreased proliferation caused by inhibition of the GABA(A receptors. This supported the depolarising role for the GABA(A receptors. Inhibition of L-type voltage-gated Ca(2+ channels (VGCCs reduced the proliferation in the same way as inhibition of the GABA(A receptors. Inhibition of the channels increased the expression of the cyclin-dependent kinase inhibitor p27(KIP1, along with the reduced proliferation. These results are consistent with that when the membrane potential indirectly regulates cell proliferation with hyperpolarisation of the membrane potential resulting in decreased cell division. The increased expression of p27(KIP1 after inhibition of either the GABA(A receptors or the L-type VGCCs suggests a link between the GABA(A receptors, membrane potential, and

  7. Selective impairment of a subset of Ran-GTP-binding domains of ran-binding protein 2 (Ranbp2) suffices to recapitulate the degeneration of the retinal pigment epithelium (RPE) triggered by Ranbp2 ablation.

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    Patil, Hemangi; Saha, Arjun; Senda, Eugene; Cho, Kyoung-in; Haque, MdEmdadul; Yu, Minzhong; Qiu, Sunny; Yoon, Dosuk; Hao, Ying; Peachey, Neal S; Ferreira, Paulo A

    2014-10-24

    Retinal pigment epithelium (RPE) degeneration underpins diseases triggered by disparate genetic lesions, noxious insults, or both. The pleiotropic Ranbp2 controls the expression of intrinsic and extrinsic pathological stressors impinging on cellular viability. However, the physiological targets and mechanisms controlled by Ranbp2 in tissue homeostasis, such as RPE, are ill defined. We show that mice, RPE-cre::Ranbp2(-/-), with selective Ranbp2 ablation in RPE develop pigmentary changes, syncytia, hypoplasia, age-dependent centrifugal and non-apoptotic degeneration of the RPE, and secondary leakage of choriocapillaris. These manifestations are accompanied by the development of F-actin clouds, metalloproteinase-11 activation, deregulation of expression or subcellular localization of critical RPE proteins, atrophic cell extrusions into the subretinal space, and compensatory proliferation of peripheral RPE. To gain mechanistic insights into what Ranbp2 activities are vital to the RPE, we performed genetic complementation analyses of transgenic lines of bacterial artificial chromosomes of Ranbp2 harboring loss of function of selective Ranbp2 domains expressed in a Ranbp2(-/-) background. Among the transgenic lines produced, only Tg(RBD2/3*-HA)::RPE-cre::Ranbp2(-/-)-expressing mutations, which selectively impair binding of RBD2/3 (Ran-binding domains 2 and 3) of Ranbp2 to Ran-GTP, recapitulate RPE degeneration, as observed with RPE-cre::Ranbp2(-/-). By contrast, Tg(RBD2/3*-HA) expression rescues the degeneration of cone photoreceptors lacking Ranbp2. The RPE of RPE-cre::Ranbp2(-/-) and Tg(RBD2/3*-HA)::RPE-cre::Ranbp2(-/-) share proteostatic deregulation of Ran GTPase, serotransferrin, and γ-tubulin and suppression of light-evoked electrophysiological responses. These studies unravel selective roles of Ranbp2 and its RBD2 and RBD3 in RPE survival and functions. We posit that the control of Ran GTPase by Ranbp2 emerges as a novel therapeutic target in diseases promoting

  8. Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo.

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    Marianne Pons

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly population. Debris (termed drusen below the retinal pigment epithelium (RPE have been recognized as a risk factor for dry AMD and its progression to wet AMD, which is characterized by choroidal neovascularization (CNV. The underlying mechanism of how drusen might elicit CNV remains undefined. Cigarette smoking, oxidative damage to the RPE and inflammation are postulated to be involved in the pathophysiology of the disease. To better understand the cellular mechanism(s linking oxidative stress and inflammation to AMD, we examined the expression of pro-inflammatory monocyte chemoattractant protein-1 (MCP-1, pro-angiogenic vascular endothelial growth factor (VEGF and anti-angiogenic pigment epithelial derived factor (PEDF in RPE from smoker patients with AMD. We also evaluated the effects of hydroquinone (HQ, a major pro-oxidant in cigarette smoke on MCP-1, VEGF and PEDF expression in cultured ARPE-19 cells and RPE/choroids from C57BL/6 mice. PRINCIPAL FINDINGS: MCP-1, VEGF and PEDF expression was examined by real-time PCR, Western blot, and ELISA. Low levels of MCP-1 protein were detected in RPE from AMD smoker patients relative to controls. Both MCP-1 mRNA and protein were downregulated in ARPE-19 cells and RPE/choroids from C57BL/6 mice after 5 days and 3 weeks of exposure to HQ-induced oxidative injury. VEGF protein expression was increased and PEDF protein expression was decreased in RPE from smoker patients with AMD versus controls resulting in increased VEGF/PEDF ratio. Treatment with HQ for 5 days and 3 weeks increased the VEGF/PEDF ratio in vitro and in vivo. CONCLUSION: We propose that impaired RPE-derived MCP-1-mediated scavenging macrophages recruitment and phagocytosis might lead to incomplete clearance of proinflammatory debris and infiltration of proangiogenic macrophages which along with increased VEGF/PEDF ratio favoring

  9. Lesion of the olfactory epithelium accelerates prion neuroinvasion and disease onset when prion replication is restricted to neurons.

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    Jenna Crowell

    Full Text Available Natural prion diseases of ruminants are moderately contagious and while the gastrointestinal tract is the primary site of prion agent entry, other mucosae may be entry sites in a subset of infections. In the current study we examined prion neuroinvasion and disease induction following disruption of the olfactory epithelium in the nasal mucosa since this site contains environmentally exposed olfactory sensory neurons that project directly into the central nervous system. Here we provide evidence for accelerated prion neuroinvasion and clinical onset from the olfactory mucosa after disruption and regeneration of the olfactory epithelium and when prion replication is restricted to neurons. In transgenic mice with neuron restricted replication of prions, there was a reduction in survival when the olfactory epithelium was disrupted prior to intranasal inoculation and there was >25% decrease in the prion incubation period. In a second model, the neurotropic DY strain of transmissible mink encephalopathy was not pathogenic in hamsters by the nasal route, but 50% of animals exhibited brain infection and/or disease when the olfactory epithelium was disrupted prior to intranasal inoculation. A time course analysis of prion deposition in the brain following loss of the olfactory epithelium in models of neuron-restricted prion replication suggests that neuroinvasion from the olfactory mucosa is via the olfactory nerve or brain stem associated cranial nerves. We propose that induction of neurogenesis after damage to the olfactory epithelium can lead to prion infection of immature olfactory sensory neurons and accelerate prion spread to the brain.

  10. X-box binding protein 1 is essential for the anti-oxidant defense and cell survival in the retinal pigment epithelium.

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    Yimin Zhong

    Full Text Available Damage to the retinal pigment epithelium (RPE is an early event in the pathogenesis of age-related macular degeneration (AMD. X-box binding protein 1 (XBP1 is a key transcription factor that regulates endoplasmic reticulum (ER homeostasis and cell survival. This study aimed to delineate the role of endogenous XBP1 in the RPE. Our results show that in a rat model of light-induced retinal degeneration, XBP1 activation was suppressed in the RPE/choroid complex, accompanied by decreased anti-oxidant genes and increased oxidative stress. Knockdown of XBP1 by siRNA resulted in reduced expression of SOD1, SOD2, catalase, and glutathione synthase and sensitized RPE cells to oxidative damage. Using Cre/LoxP system, we generated a mouse line that lacks XBP1 only in RPE cells. Compared to wildtype littermates, RPE-XBP1 KO mice expressed less SOD1, SOD2, and catalase in the RPE, and had increased oxidative stress. At age 3 months and older, these mice exhibited apoptosis of RPE cells, decreased number of cone photoreceptors, shortened photoreceptor outer segment, reduced ONL thickness, and deficit in retinal function. Electron microscopy showed abnormal ultrastructure, Bruch's membrane thickening, and disrupted basal membrane infolding in XBP1-deficient RPE. These results indicate that XBP1 is an important gene involved in regulation of the anti-oxidant defense in the RPE, and that impaired activation of XBP1 may contribute to RPE dysfunction and cell death during retinal degeneration and AMD.

  11. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex.

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    Bhutto, Imran; Lutty, Gerard

    2012-08-01

    There is a mutualistic symbiotic relationship between the components of the photoreceptor/retinal pigment epithelium (RPE)/Bruch's membrane (BrMb)/choriocapillaris (CC) complex that is lost in AMD. Which component in the photoreceptor/RPE/BrMb/CC complex is affected first appears to depend on the type of AMD. In atrophic AMD (~85-90% of cases), it appears that large confluent drusen formation and hyperpigmentation (presumably dysfunction in RPE) are the initial insult and the resorption of these drusen and loss of RPE (hypopigmentation) can be predictive for progression of geographic atrophy (GA). The death and dysfunction of photoreceptors and CC appear to be secondary events to loss in RPE. In neovascular AMD (~10-15% of cases), the loss of choroidal vasculature may be the initial insult to the complex. Loss of CC with an intact RPE monolayer in wet AMD has been observed. This may be due to reduction in blood supply because of large vessel stenosis. Furthermore, the environment of the CC, basement membrane and intercapillary septa, is a proinflammatory milieu with accumulation of complement components as well as proinflammatory molecules like CRP during AMD. In this toxic milieu, CC die or become dysfunction making adjacent RPE hypoxic. These hypoxic cells then produce angiogenic substances like VEGF that stimulate growth of new vessels from CC, resulting in choroidal neovascularization (CNV). The loss of CC might also be a stimulus for drusen formation since the disposal system for retinal debris and exocytosed material from RPE would be limited. Ultimately, the photoreceptors die of lack of nutrients, leakage of serum components from the neovascularization, and scar formation. Therefore, the mutualistic symbiotic relationship within the photoreceptor/RPE/BrMb/CC complex is lost in both forms of AMD. Loss of this functionally integrated relationship results in death and dysfunction of all of the components in the complex.

  12. A Possible Role of Acrolein in Diabetic Retinopathy: Involvement of a VEGF/TGFβ Signaling Pathway of the Retinal Pigment Epithelium in Hyperglycemia

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    Grigsby, Jeffery; Betts, Brandi; Vidro-Kotchan, Eileen; Culbert, Richard; Tsin, Andrew

    2015-01-01

    Purpose Acrolein has been implicated in retinal pigment epithelium (RPE) cell death, and has been associated with diabetic retinopathy. Our purpose was to investigate the potential effect of high glucose in influencing acrolein-mediated RPE cytokine production and cell death. We investigated the influence of the acrolein effect on ARPE-19 cells in high glucose conditions and quantified the release of transforming growth factor β (TGFβ1 and 2) and vascular endothelial growth factor (VEGF). We assessed the ability of N-benzylhydroxylamine(NBHA) as well as TGFβ pathway inhibitors SIS3 and SB431542 to prevent this effect of acrolein on ARPE-19 cells. Materials and methods Confluent ARPE-19 cells were treated with acrolein and/or NBHA in both 5.5 and 18.8 mM glucose conditions. Cells were also pretreated with SIS3, a specific inhibitor of the SMAD3 pathway, and SB431542, a specific inhibitor of TGFβ signaling pathway, before treating them with acrolein. Viable cells were counted and ELISAs were performed to measure the cytokines TGFβ1 and 2, and VEGF released into the conditioned media. Results In ARPE-19 cells exposed to acrolein and hyperglycemia there was reduced cell viability and an increase in the cell media of VEGF, TGFβ1, and TGFβ2, which was reversed by NBHA. Acrolein/hyperglycemia-induced cell viability reduction and cytokine overproduction was also reduced by TGFβ pathway blockade. Conclusions We conclude that the effect of acrolein on the reduction of viability and VEGF increase by ARPE-19 cells in hyperglycemic media is conducted through the TGFβ signaling pathway. Our results suggest that benefits of sequestering acrolein by NBHA and the blockage of the TGFβ pathway by SB431542 and SIS3 offer suggestions as to potential useful pharmacological drug candidates for the prevention of diabetes-induced complications in the eye. PMID:22906079

  13. Complement Factor H Expressed by Retinal Pigment Epithelium Cells Can Suppress Neovascularization of Human Umbilical Vein Endothelial Cells: An in vitro Study.

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    Yi Zhang

    Full Text Available Complement factor H (CFH is one of the most important soluble complement regulatory proteins and is closely associated with age-related macular degeneration (AMD, the leading cause of irreversible central vision loss in the elderly population in developed countries. Our study searches to investigate whether CFH expression is changed in oxidative damaged retinal pigment epithelium (RPE cells and the role of CFH in the in vitro neovascularization. First, it was confirmed by immunofluorescence staining that CFH was expressed by ARPE-19 cells. CFH mRNA and protein in oxidative (H2O2 damaged ARPE-19 cells were both reduced, as determined by Real-time PCR and Western blotting analysis. Enzyme-linked immunosorbent assay (ELISA also showed that ARPE-19 cells treated with H2O2 caused an increase in C3a content, which indicates complement activation. Then, wound assays were performed to show that CFH expression suppression promoted human umbilical vein endothelial cell (HUVECs migration. Thereafter, ARPE-19 cells were transfected with CFH-specific siRNA and CFH knockdown was confirmed with the aid of Real-time PCR, immunofluorescence staining and Western blotting. The ELISA results showed that specific CFH knockdown in ARPE-19 cells activated the complement system. Finally, in vitro matrigel tube formation assay was performed to determine whether change of CFH expression in RPE would affect tube formation by HUVECs. More tubes were formed by HUVECs co-cultured with ARPE-19 cells transfected with CFH specific-siRNA when compared with controls. Our results suggested that RPE cells might be the local CFH source, and RPE cell injuries (such as oxidative stress may cause CFH expression suppression, which in turn may lead to complement activation and promotion of tube formation by HUVECs. This finding is of importance in elucidating the role of complement in the pathogenesis of ocular neovascularization including choroidal neovascularization.

  14. Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats,

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    Guilherme Silva Julian

    2015-02-01

    Full Text Available Objective: Obstructive sleep apnea syndrome is mainly characterized by intermittent hypoxia (IH during sleep, being associated with several complications. Exposure to IH is the most widely used animal model of sleep apnea, short-term IH exposure resulting in cognitive and neuronal impairment. Pigment epithelium-derived factor (PEDF is a hypoxia-sensitive factor acting as a neurotrophic, neuroprotective, and antiangiogenic agent. Our study analyzed performance on learning and cognitive tasks, as well as PEDF gene expression and PEDF protein expression in specific brain structures, in rats exposed to long-term IH. Methods: Male Wistar rats were exposed to IH (oxygen concentrations of 21-5% for 6 weeks-the chronic IH (CIH group-or normoxia for 6 weeks-the control group. After CIH exposure, a group of rats were allowed to recover under normoxic conditions for 2 weeks (the CIH+N group. All rats underwent the Morris water maze test for learning and memory, PEDF gene expression and PEDF protein expression in the hippocampus, frontal cortex, and temporal cortex being subsequently assessed. Results: The CIH and CIH+N groups showed increased PEDF gene expression in the temporal cortex, PEDF protein expression remaining unaltered. PEDF gene expression and PEDF protein expression remained unaltered in the frontal cortex and hippocampus. Long-term exposure to IH did not affect cognitive function. Conclusions: Long-term exposure to IH selectively increases PEDF gene expression at the transcriptional level, although only in the temporal cortex. This increase is probably a protective mechanism against IH-induced injury.

  15. Pigment epithelium-derived factor and diabetic nephropathy%色素上皮衍生因子与糖尿病肾病

    Institute of Scientific and Technical Information of China (English)

    李珍瑾; 李竞

    2008-01-01

    色素上皮衍生因子(PEDF)是一种高效、天然的血管增生抑制剂,具有神经营养保护、调节血管通透性和高效抑制血管生成等作用.近年来有研究表明,PEDF的减少与糖尿病肾病(DN)有密切关系,PEDF可抑制转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)的表达,抑制细胞外基质(ECM)的聚积,提示其具有抗纤维化活性,同时可通过调节肾脏脉管系统发展和维持肾自身稳态来发挥对DN的保护作用.PEDF可抑制DN的发生、发展,可能成为DN治疗的一种新方向.%Pigment epithelium-derived factor(PEDF)is an efficient natural angiogenic inhibitor that can protect neuronal nutrition,regulate vascular permeability and antiangiogenie activity.Recent studies show that the decrease of PEDF levels may be closely involved in diabetic nephmpathy(DN).PEDF inhibits the expression of TGF-β1 and CTGF,and suppresses the production of ECM protein in diabetic kidney,suggesting it has antifibrogenic activity.Meanwhile,PEDF phys a role in regulating the development of renal vasculature and maintenance of renal homeostasis,and may be responsible for its salutary effect in DN.PEDF can inhibit the occurrence and development of DN,and may become a new target for the treatment of DN.

  16. Blockade of Jagged/Notch pathway abrogates transforming growth factor β2-induced epithelial-mesenchymal transition in human retinal pigment epithelium cells.

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    Chen, X; Xiao, W; Liu, X; Zeng, M; Luo, L; Wu, M; Ye, S; Liu, Y

    2014-05-01

    The epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays a key role in proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR), which lead to the loss of vision. The Jagged/Notch pathway has been reported to be essential in EMT during embryonic development, fibrotic diseases and cancer metastasis. However, the function of Jagged/Notch signaling in EMT of RPE cells is unknown. Thus, we hypothesized that a crosstalk between Notch and transforming growth factor β2 (TGF-β2) signaling could induce EMT in RPE cells, which subsequently contributes to PVR and PDR. Here, we demonstrate that Jagged-1/Notch pathway is involved in the TGF-β2-mediated EMT of human RPE cells. Blockade of Notch pathway with DAPT (a specific inhibitor of Notch receptor cleavage) and knockdown of Jagged-1 expression inhibited TGF-β2-induced EMT through regulating the expression of Snail, Slug and ZEB1. Besides the canonical Smad signaling pathway, the noncanonical PI3K/Akt and MAPK pathway also contributed to TGF-β2-induced up-regulation of Jagged-1 in RPE cells. Overexpression of Jagged-1 could mimic TGF-β2 induce EMT. Our data suggest that the Jagged-1/Notch signaling pathway plays a critical role in TGF-β2-induced EMT in human RPE cells, and may contribute to the development of PVR and PDR. Inhibition of the Jagged/Notch signaling pathway, therefore, may have therapeutic value in the prevention and treatment of PVR and PDR.

  17. 色素上皮细胞源性因子的抗肿瘤活性%Anti-tumor effects of pigment epithelium-derived factor

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    任远; 张锡林

    2011-01-01

    色素上皮细胞源性因子(PEDF)是一种最早从人类胚胎视网膜色素上皮中发现的相对分子质量约为50 KDa的分泌糖蛋白.PEDF广泛存在于人体内多个器官和组织中,且其表达量与人体内多项病理生理过程密切相关.最近研究表明,PEDF在肿瘤的生长、侵袭和转移过程中发挥着重要作用.肿瘤组织中的微血管密度与肿瘤的生长速度呈正相关,作为目前已知的最强的内源性血管生成抑制因子,PEDF能够通过抑制肿瘤血管生成而抑制肿瘤的生长.此外,PEDF亦能通过激活多种复杂信号转导通路诱导肿瘤细胞的凋亡.%PEDF is a 50-kDa secreted glycoprotein first discovered as a factor secreted by the retina pigmented epithelium of the human foetal eye. PEDF is widely spread in human tissues and organs, and its expression is related to the function of human body. Recent studies have shown that PEDF plays an important role in tumor growth, invasion, and metastasis. As we know, microvessel density is correlated with the rapid growth of tumor cells. As the most potent endogenous angiogenesis inhibitor, PEDF can suppress tumor growth by inhibiting angiogenesis. In addition, PEDF can also induce apoptosis through activating complex signal transduction pathways.

  18. Retina-specific nuclear receptor: A potential regulator of cellular retinaldehyde-binding protein expressed in retinal pigment epithelium and Müller glial cells.

    Science.gov (United States)

    Chen, F; Figueroa, D J; Marmorstein, A D; Zhang, Q; Petrukhin, K; Caskey, C T; Austin, C P

    1999-12-21

    In an effort to identify nuclear receptors important in retinal disease, we screened a retina cDNA library for nuclear receptors. Here we describe the identification of a retina-specific nuclear receptor (RNR) from both human and mouse. Human RNR is a splice variant of the recently published photoreceptor cell-specific nuclear receptor [Kobayashi, M., Takezawa, S., Hara, K., Yu, R. T., Umesono, Y., Agata, K., Taniwaki, M., Yasuda, K. & Umesono, K. (1999) Proc. Natl. Acad. Sci. USA 96, 4814-4819] whereas the mouse RNR is a mouse ortholog. Northern blot and reverse transcription-PCR analyses of human mRNA samples demonstrate that RNR is expressed exclusively in the retina, with transcripts of approximately 7.5 kb, approximately 3.0 kb, and approximately 2.3 kb by Northern blot analysis. In situ hybridization with multiple probes on both primate and mouse eye sections demonstrates that RNR is expressed in the retinal pigment epithelium and in Müller glial cells. By using the Gal4 chimeric receptor/reporter cotransfection system, the ligand binding domain of RNR was found to repress transcriptional activity in the absence of exogenous ligand. Gel mobility shift assays revealed that RNR can interact with the promoter of the cellular retinaldehyde binding protein gene in the presence of retinoic acid receptor (RAR) and/or retinoid X receptor (RXR). These data raise the possibility that RNR acts to regulate the visual cycle through its interaction with cellular retinaldehyde binding protein and therefore may be a target for retinal diseases such as retinitis pigmentosa and age-related macular degeneration.

  19. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.

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    Lakeland, Thomas V; Borg, Melissa L; Matzaris, Maria; Abdelkader, Amany; Evans, Roger G; Watt, Matthew J

    2014-06-15

    Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo. Copyright © 2014 the American Physiological Society.

  20. Angiotensin-2-mediated Ca2+ signaling in the retinal pigment epithelium: role of angiotensin-receptor-associated-protein and TRPV2 channel.

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    Rene Barro-Soria

    Full Text Available Angiotensin II (AngII receptor (ATR is involved in pathologic local events such as neovascularisation and inflammation including in the brain and retina. The retinal pigment epithelium (RPE expresses ATR in its AT1R form, angiotensin-receptor-associated protein (Atrap, and transient-receptor-potential channel-V2 (TRPV2. AT1R and Atrap co-localize to the basolateral membrane of the RPE, as shown by immunostaining. Stimulation of porcine RPE (pRPE cells by AngII results in biphasic increases in intracellular free Ca(2+inhibited by losartan. Xestospongin C (xest C and U-73122, blockers of IP3R and PLC respectively, reduced AngII-evoked Ca(2+response. RPE cells from Atrap(-/- mice showed smaller AngII-evoked Ca(2+peak (by 22% and loss of sustained Ca(2+elevation compared to wild-type. The TRPV channel activator cannabidiol (CBD at 15 µM stimulates intracellular Ca(2+-rise suggesting that porcine RPE cells express TRPV2 channels. Further evidence supporting the functional expression of TRPV2 channels comes from experiments in which 100 µM SKF96365 (a TRPV channel inhibitor reduced the cannabidiol-induced Ca(2+-rise. Application of SKF96365 or reduction of TRPV2 expression by siRNA reduced the sustained phase of AngII-mediated Ca(2+transients by 53%. Thus systemic AngII, an effector of the local renin-angiotensin system stimulates biphasic Ca(2+transients in the RPE by releasing Ca(2+from cytosolic IP3-dependent stores and activating ATR/Atrap and TRPV2 channels to generate a sustained Ca(2+elevation.

  1. Review of spectral domain-enhanced depth imaging optical coherence tomography of tumors of the retina and retinal pigment epithelium in children and adults

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    Carol L Shields

    2015-01-01

    Full Text Available Background: Spectral domain (SD enhanced depth imaging optical coherence tomography (EDI-OCT is a useful tool for anatomic, cross-sectional imaging of retinal conditions. Aims: The aim was to identify characteristic patterns of retinal and retinal pigment epithelial tumors on EDI-OCT in children and adults. Settings and Design: Retrospective review. Materials and Methods: Analysis of published reports and personal observations using office-based EDI-OCT for adults and portable hand-held SD OCT for infants and children. Results: Using EDI-OCT, retinal tumors such as small retinoblastoma, astrocytic hamartoma, and hemangioblastoma arose abruptly from the retina, immediately adjacent to normal retina. Small exophytic retinoblastoma and retinal hemangioblastoma showed the full-thickness, homogeneous retinal disorganization with surrounding normal retina "draping" over the margins. Retinoblastoma occasionally had intralesional cavities and surrounding subretinal fluid. Hemangioblastoma often had adjacent intraretinal edema and subretinal fluid. Astrocytic hamartoma arose within the nerve fiber layer and sometimes with a "moth-eaten" or cavitary appearance. Retinal pigment epithelial (RPE lesions such as congenital hypertrophy of RPE appeared flat with shadowing, occasional subretinal cleft, and abrupt photoreceptor loss. Congenital simple hamartoma showed an abrupt elevation from the inner retina with crisp, dark posterior shadowing. Combined hamartoma of the retina/RPE showed vitreoretinal traction causing "sawtooth mini-peak" or gently "maxi-peak" folding of the retina. RPE adenoma often produces remote macular edema or epiretinal membrane and the tumor has an irregular, "rugged" surface with deep shadowing. Conclusions: Enhanced depth imaging optical coherence tomography shows characteristic patterns that are suggestive of certain retinal and RPE tumors.

  2. Oral pigmentation: A review.

    Science.gov (United States)

    Sreeja, C; Ramakrishnan, K; Vijayalakshmi, D; Devi, M; Aesha, I; Vijayabanu, B

    2015-08-01

    Pigmentations are commonly found in the mouth. They represent in various clinical patterns that can range from just physiologic changes to oral manifestations of systemic diseases and malignancies. Color changes in the oral mucosa can be attributed to the deposition of either endogenous or exogenous pigments as a result of various mucosal diseases. The various pigmentations can be in the form of blue/purple vascular lesions, brown melanotic lesions, brown heme-associated lesions, gray/black pigmentations.

  3. Prehistological evaluation of benign and malignant pigmented skin lesions with optical computed tomography

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    Kokolakis, Athanasios; Zacharakis, Giannis; Krasagakis, Konstantin; Lasithiotakis, Konstantinos; Favicchio, Rosy; Spiliopoulos, George; Giannikaki, Elpida; Ripoll, Jorge; Tosca, Androniki

    2012-06-01

    Discrimination of benign and malignant melanocytic lesions is a major issue in clinical dermatology. Assessment of the thickness of melanoma is critical for prognosis and treatment selection. We aimed to evaluate a novel optical computed tomography (optical-CT) system as a tool for three-dimensional (3-D) imaging of melanocytic lesions and its ability to discriminate benign from malignant melanocytic lesions while simultaneously determining the thickness of invasive melanoma. Seventeen melanocytic lesions, one hemangioma, and normal skin were assessed immediately after their excision by optical-CT and subsequently underwent histopathological examination. Tomographic reconstructions were performed with a back-propagation algorithm calculating a 3-D map of the total attenuation coefficient (AC). There was a statistically significant difference between melanomas, dysplastic nevi, and non-dysplastic nevi, as indicated by Kruskal-Wallis test. Median AC values were higher for melanomas compared with dysplastic and non-dysplastic nevi. No statistically significant difference was observed when thickness values obtained by optical-CT were compared with histological thickness using a Wilcoxon sighed rank test. Our results suggest that optical-CT can be important for the immediate prehistological evaluation of biopsies, assisting the physician for a rapid assessment of malignancy and of the thickness of a melanocytic lesion.

  4. The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser. A comparative study.

    Science.gov (United States)

    Tse, Y; Levine, V J; McClain, S A; Ashinoff, R

    1994-12-01

    The Q-switched ruby laser (QSRL) (694 nm) has been used successfully in the removal of tattoos and a variety of cutaneous pigmented lesions. The frequency-doubled Q-switched neodymium:yttrium-aluminum-garnet laser (QSNd:YAG) (1064 and 532 nm) has also been shown to be effective in the treatment of tattoos, however, little has been published regarding the QSNd:YAG laser in the removal of cutaneous pigmented lesions. The purpose of this study is to compare the efficacy and side effect profile of the QSRL and the frequency-doubled QSNd:YAG lasers in the removal of cutaneous pigmented lesions, including lentigines, café-au-lait macules, nevus of Ota, nevus spilus, Becker's nevus, postinflammatory hyperpigmentation, and melasma. Twenty patients with pigmented lesions were treated with the QSRL and the frequency-doubled QSNd:YAG lasers. Clinical lightening of the lesion was assessed 1 month after a single treatment. Side effects and patient satisfaction were also evaluated. A minimum of 30% lightening was achieved in all patients after only one treatment with either the QSRL or the frequency-doubled QSNd:YAG laser. The QSRL seems to provide a slightly better treatment response than the QSNd:YAG laser. Neither laser caused scarring or textural change of the skin. Most patients found the QSRL to be more painful during treatment, but the QSNd:YAG laser caused more postoperative discomfort. Both the QSRL and the frequency-doubled QSND:YAG laser are safe and effective methods of treatment of epidermal and dermal pigmented lesions.

  5. Tumorigenicity studies of induced pluripotent stem cell (iPSC-derived retinal pigment epithelium (RPE for the treatment of age-related macular degeneration.

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    Hoshimi Kanemura

    Full Text Available Basic studies of human pluripotential stem cells have advanced rapidly and stem cell products are now seeing therapeutic applications. However, questions remain regarding the tumorigenic potential of such cells. Here, we report the tumorigenic potential of induced pluripotent stem cell (iPSC-derived retinal pigment epithelium (RPE for the treatment of wet-type, age-related macular degeneration (AMD. First, immunodeficient mouse strains (nude, SCID, NOD-SCID and NOG were tested for HeLa cells' tumor-forming capacity by transplanting various cell doses subcutaneously with or without Matrigel. The 50% Tumor Producing Dose (TPD50 value is the minimal dose of transplanted cells that generated tumors in 50% of animals. For HeLa cells, the TPD50 was the lowest when cells were embedded in Matrigel and transplanted into NOG mice (TPD50 = 10(1.1, n = 75. The TPD50 for undifferentiated iPSCs transplanted subcutaneously to NOG mice in Matrigel was 10(2.12; (n = 30. Based on these experiments, 1×10(6 iPSC-derived RPE were transplanted subcutaneously with Matrigel, and no tumor was found during 15 months of monitoring (n = 65. Next, to model clinical application, we assessed the tumor-forming potential of HeLa cells and iPSC 201B7 cells following subretinal transplantation of nude rats. The TPD50 for iPSCs was 10(4.73 (n = 20 and for HeLa cells 10(1.32 (n = 37 respectively. Next, the tumorigenicity of iPSC-derived RPE was tested in the subretinal space of nude rats by transplanting 0.8-1.5×10(4 iPSC-derived RPE in a collagen-lined (1 mm×1 mm sheet. No tumor was found with iPSC-derived RPE sheets during 6-12 months of monitoring (n = 26. Considering the number of rodents used, the monitoring period, the sensitivity of detecting tumors via subcutaneous and subretinal administration routes and the incidence of tumor formation from the iPSC-derived RPE, we conclude that the tumorigenic potential of the iPSC-derived RPE was

  6. Specific interaction of Gαi3 with the Oa1 G-protein coupled receptor controls the size and density of melanosomes in retinal pigment epithelium.

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    Alejandra Young

    Full Text Available BACKGROUND: Ocular albinism type 1, an X-linked disease characterized by the presence of enlarged melanosomes in the retinal pigment epithelium (RPE and abnormal crossing of axons at the optic chiasm, is caused by mutations in the OA1 gene. The protein product of this gene is a G-protein-coupled receptor (GPCR localized in RPE melanosomes. The Oa1-/- mouse model of ocular albinism reproduces the human disease. Oa1 has been shown to immunoprecipitate with the Gαi subunit of heterotrimeric G proteins from human skin melanocytes. However, the Gαi subfamily has three highly homologous members, Gαi1, Gαi2 and Gαi3 and it is possible that one or more of them partners with Oa1. We had previously shown by in-vivo studies that Gαi3-/- and Oa1-/- mice have similar RPE phenotype and decussation patterns. In this paper we analyze the specificity of the Oa1-Gαi interaction. METHODOLOGY: By using the genetic mouse models Gαi1-/-, Gαi2-/-, Gαi3-/- and the double knockout Gαi1-/-, Gαi3-/- that lack functional Gαi1, Gαi2, Gαi3, or both Gαi1 and Gαi3 proteins, respectively, we show that Gαi3 is critical for the maintenance of a normal melanosomal phenotype and that its absence is associated with changes in melanosomal size and density. GST-pull-down and immunoprecipitation assays conclusively demonstrate that Gαi3 is the only Gαi that binds to Oa1. Western blots show that Gαi3 expression is barely detectable in the Oa1-/- RPE, strongly supporting a previously unsuspected role for Gαi3 in melanosomal biogenesis. CONCLUSION: Our results identify the Oa1 transducer Gαi3 as the first downstream component in the Oa1 signaling pathway.

  7. The 'common mole' from the point of view of digital dermoscopy analysis: subjective vs. objective evaluation of easy pigmented skin lesions.

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    Burroni, M; Rubegni, P; Dell'eva, G; Santini, S; Perotti, R; Biagioli, M; Taddeucci, P; Andreassi, L

    2003-01-01

    The term 'common mole', often used to describe a subset of benign pigmented skin lesions, is traditionally defined on the basis of morpho-chromatic features. In recent years, certain research groups have developed equipment and methods, such as digital dermoscopy analysis, that enable objective evaluation of pigmented skin lesions. In this study we use a digital dermoscopy analyser trained for the recognition of pigmented skin lesions to compare the subjective definition of 'common' and the mathematical concept of 'close to the mean of measurements'. A subset (100) of digital images of flat pigmented lesions, obtained in daily practice, were classified by trained and non-expert clinicians as common moles (60) or clear-cut melanoma (40), and processed with a DB-Mips analyser. The resulting parameters, validated by a classifier, were used to evaluate Hotelling's T2 multivariate distances from the mean. 'Common' moles could not be clearly defined in terms of closeness to the means of objectively evaluated parameters. Their diagnosis indudes many other evaluations and clusters of variables. The clinical semantics of the term 'common' does not conform to any unambiguous mathematical definition.

  8. Pulsed dye laser treatment of pigmented lesions: a randomized clinical pilot study comparison of 607- and 595-nm wavelength lasers.

    Science.gov (United States)

    Chern, Peggy L; Domankevitz, Yacov; Ross, E Victor

    2010-12-01

    The 595-nm pulsed dye laser has been used for the treatment of benign epidermal pigmented lesions (EPLs), but there is a risk of inducing undesirable purpura with treatment. To compare a 607-nm laser with a commercially-available 595-nm laser for the treatment of EPLs. Monte-Carlo simulations were performed to characterize laser interaction with skin. Ten patients with EPLs were treated with a 607-nm study prototype laser and the 595-nm pulsed dye laser twice at 2- to 4-week intervals on the left or right side on a randomized basis. Study endpoints included clearance rate of lesions, side effects immediately after treatment and at final follow-up, and patient discomfort/pain. Monte-Carlo simulations show that the 607-nm is absorbed more specifically by melanin than the 595-nm wavelength. Both lasers were effective in treatment of EPLs. The average degree of improvement overall was 41.2% with the 607-nm laser and 40% with the 595-nm laser. Patients reported less discomfort/pain during treatment with the 607-nm laser. Our findings suggest that the 607-nm laser is safe and at least as effective as the 595-nm laser in treatment of EPLs. There was less patient discomfort/pain during treatment using the 607-nm laser. Copyright © 2010 Wiley-Liss, Inc.

  9. Iris pigment epithelial cysts in a newborn

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    Zargar, Shabnam

    2016-04-01

    Full Text Available Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia.Methods: We describe a case of an abnormal red reflex seen on a newborn exam.Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2– dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months.Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia.

  10. A fractal analysis of skin pigmented lesions using the novel tool of the variogram technique

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    Mastrolonardo, Mario [Department of Medical and Occupational Sciences, Unit of Dermatology, Azienda Ospedaliero-Universitaria ' Ospedali Riuniti' di Foggia (Italy)]. E-mail: mariomastrolonardo@libero.it; Conte, Elio [Department of Medical and Occupational Sciences, Unit of Dermatology, Azienda Ospedaliero-Universitaria ' Ospedali Riuniti' di Foggia (Italy); Department of Pharmacology and Human Physiology, TIRES-Center for Innovative Technology for Signal Detection and Processing, Bari University, 70100 Bari (Italy); Zbilut, Joseph P. [Department of Molecular Biophysics and Physiology, Rush University, Chicago, IL 60612 (United States)

    2006-06-15

    The incidence of the cutaneous malignant melanoma is increasing rapidly in the world [Ferlay J, Bray F, Pisani P, et al. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, Version 1.0 IARC Cancer Base no. 5. Lyon: IARC Press, 2001]. The therapeutic address requires a method having high sensitivity and capability to diagnose such disease at an early stage. We introduce a new diagnostic method based on non-linear methodologies. In detail we suggest that fractal as well as noise and chaos dynamics are the most important components responsible for genetic instability of melanocytes. As consequence we introduce the new technique of the variogram and of fractal analysis extended to the whole regions of interest of skin in order to obtain parameters able to identify the malignant lesion. In a preliminary analysis, satisfactory results are reached.

  11. Retinal pigment epithelium protein of 65 kDA gene-linked retinal degeneration is not modulated by chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C/ chondroitin sulfate proteoglycan 5.

    Science.gov (United States)

    Cottet, Sandra; Jüttner, René; Voirol, Nathalie; Chambon, Pierre; Rathjen, Fritz G; Schorderet, Daniel F; Escher, Pascal

    2013-01-01

    To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65⁻/⁻ mouse model of Leber congenital amaurosis. We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5⁻/⁻/Rpe65⁻/⁻). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Transcriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin α subunit (Gnat1), and cone transducin α subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. No differences in the progression of retinal degeneration were observed between the Rpe65⁻/⁻ and Cspg5⁻/⁻/Rpe65⁻/⁻ mice. No retinal phenotype was detected in the late postnatal and adult Cspg5⁻/⁻ mice, when compared to the wild-type mice. Despite the previously reported upregulation of Cspg5 during retinal degeneration in Rpe65⁻/⁻ mice, no protective effect or any involvement of Cspg5 in disease progression was identified.

  12. Transplante autólogo do epitélio pigmentado da retina na degeneração macular relacionada com a idade Autologous transplantation of retinal pigment epithelium in age related macular degeneration

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    Rubens Camargo Siqueira

    2009-02-01

    Full Text Available Acredita-se que a disfunção do epitélio pigmentado da retina é a principal causa de muitas doenças debilitantes da retina das quais a degeneração macular relacionada com a idade é a mais comum. Nesta doença a disfunção das células do epitélio pigmentado da retina leva a um comprometimento secundário dos fotorreceptores com perda visual grave. O epitélio pigmentado da retina e membrana de Bruch sofrem dano acumulativo com o tempo o qual induz à degeneração macular relacionada com a idade em indivíduos susceptíveis. Nos últimos 20 anos, uma grande quantidade de pesquisas tem sido conduzida na área de transplante do epitélio pigmentado da retina. A técnica tem como objetivo, restaurar a anatomia sub-retiniana e restabelecer a interação crítica entre o epitélio pigmentado da retina e o fotorreceptor, o qual é fundamental para a visão. O transplante autólogo do epitélio pigmentado da retina tem sido usado em alguns casos de degeneração macular relacionada com a idade através de duas técnicas: epitélio pigmentado da retina em suspensão e transplante de espessura total do epitélio pigmentado da retina-coróide. Apesar da viabilidade desta técnica, pesquisas buscando uma fonte de células para repor epitélio pigmentado da retina autólogo como células-tronco embrionárias, células-tronco derivadas da medula óssea e derivadas do cordão umbilical continuam em andamento. A combinação do transplante de células com outras modalidades de tratamento como transferência de genes permanecem como excitante perspectiva futura.Retinal pigment epithelial dysfunction is believed to be the main cause of many debilitating retinal diseases of which age-related macular degeneration is the most common. In this disease, the retinal pigment epithelial dysfunction leads to photoreceptors damage causing severe vision loss. The retinal pigment epithelium and Bruch's membrane suffer cumulative damage over lifetime, which is

  13. Pigmented epidermal cyst with dense collection of melanin: A rare entity - Report of a case with review of the literature.

    Science.gov (United States)

    Jayalakshmy, P S; Subitha, K; Priya, P V; Johnson, Gerald

    2012-05-01

    Epidermal cyst is a very common benign cystic lesion of the skin. It is usual to find ulceration of the lining epithelium, rupture of the cyst wall with chronic inflammation and foreign body giant cell reaction. But, it is very rare to see an epidermal cyst with marked accumulation of melanin pigment. Only a few cases of pigmented epidermal cyst with dense collection of melanin pigment have been published in the literature. Here, we are reporting a case of ruptured epidermal cyst with keratin granuloma formation and showing dense collection of melanin pigment.

  14. Molecular imaging of melanin distribution in vivo and quantitative differential diagnosis of human pigmented lesions using label-free harmonic generation biopsy (Conference Presentation)

    Science.gov (United States)

    Sun, Chi-Kuang; Wei, Ming-Liang; Su, Yu-Hsiang; Weng, Wei-Hung; Liao, Yi-Hua

    2017-02-01

    Harmonic generation microscopy is a noninvasive repetitive imaging technique that provides real-time 3D microscopic images of human skin with a sub-femtoliter resolution and high penetration down to the reticular dermis. In this talk, we show that with a strong resonance effect, the third-harmonic-generation (THG) modality provides enhanced contrast on melanin and allows not only differential diagnosis of various pigmented skin lesions but also quantitative imaging for longterm tracking. This unique capability makes THG microscopy the only label-free technique capable of identifying the active melanocytes in human skin and to image their different dendriticity patterns. In this talk, we will review our recent efforts to in vivo image melanin distribution and quantitatively diagnose pigmented skin lesions using label-free harmonic generation biopsy. This talk will first cover the spectroscopic study on the melanin enhanced THG effect in human cells and the calibration strategy inside human skin for quantitative imaging. We will then review our recent clinical trials including: differential diagnosis capability study on pigmented skin tumors; as well as quantitative virtual biopsy study on pre- and post- treatment evaluation on melasma and solar lentigo. Our study indicates the unmatched capability of harmonic generation microscopy to perform virtual biopsy for noninvasive histopathological diagnosis of various pigmented skin tumors, as well as its unsurpassed capability to noninvasively reveal the pathological origin of different hyperpigmentary diseases on human face as well as to monitor the efficacy of laser depigmentation treatments. This work is sponsored by National Health Research Institutes.

  15. The treatment of benign pigmented lesions and tattoos with the Q-switched ruby laser. A comparative study using the 5.0- and 6.5-mm spot size.

    Science.gov (United States)

    Nehal, K S; Levine, V J; Ashinoff, R

    1996-08-01

    The Q-switched ruby laser (QSRL) is useful in the treatment of benign pigmented lesions and tattoos. Two spot sizes are available in the QSRL (5 and 6.5 mm). It has not been shown if one spot size is more efficacious in the treatment of benign pigmented lesions and tattoos. The purpose of this study is to compare the clinical lightening and side effects observed with the 5.0- and 6.5-mm spot sizes of the QSRL in the treatment of benign pigmented lesions and tattoos. Eleven patients with 12 benign pigmented lesions or tattoos were prospectively studied with the QSRL. Half of the lesion was treated with the 5.0-mm spot size while the other half was treated with the 6.5-mm spot size. Clinical lightening of the lesion was assessed using pretreatment and posttreatment photographs. No significant clinical difference in the lightening of lesions or in the side effect profile was observed with either spot size. The 5.0- and 6.5-mm spot sizes of the QSRL are equally efficacious in the removal of benign pigmented lesions and tattoos. It seems prudent to use the 6.5-mm spot size when treating large lesions to reduce treatment time, patient discomfort, and treatment cost.

  16. Sexual experience does not compensate for the disruptive effects of zinc sulfate--lesioning of the main olfactory epithelium on sexual behavior in male mice.

    Science.gov (United States)

    Keller, Matthieu; Douhard, Quentin; Baum, Michael J; Bakker, Julie

    2006-10-01

    Recent studies point to an important role for the main olfactory epithelium (MOE) in regulating sexual behavior in male mice. We asked whether sexual experience could compensate for the disruptive effects of lesioning the MOE on sexual behavior in male mice. Male mice, which were either sexually naive or experienced, received an intranasal irrigation of either a zinc sulfate solution to destroy the MOE or saline. Sexual behavior in mating tests with an estrous female was completely abolished in zinc sulfate-treated male mice regardless of whether subjects were sexually experienced or not before the treatment. Furthermore, zinc sulfate treatment clearly disrupted olfactory investigation of both volatile and nonvolatile odors. Destruction of the MOE by zinc sulfate treatment was confirmed by a significant reduction in the expression of Fos protein in the main olfactory bulb following exposure to estrous female urine. By contrast, vomeronasal function did not seem to be affected by zinc sulfate treatment: nasal application of estrous female urine induced similar levels of Fos protein in the mitral and granule cells of the accessory olfactory bulb (AOB) of zinc sulfate- and saline-treated males. Likewise, the expression of soybean agglutinin, which stains the axons of vomeronasal organ neurons projecting to the glomerular layer of the AOB, was similar in zinc sulfate- and saline-treated male mice. These results show that the main olfactory system is essential for the expression of sexual behavior in male mice and that sexual experience does not overcome the disruptive effects of MOE lesioning on this behavior.

  17. Early diagnosis of malignant melanoma: Proposal of a working formulation for the management of cutaneous pigmented lesions from the Melanoma Cooperative Group.

    Science.gov (United States)

    Ascierto, Paolo A; Palmieri, Giuseppe; Botti, Gerardo; Satriano, Rocco A; Stanganelli, Ignazio; Bono, Riccardo; Testori, Alessandro; Bosco, Leonardo; Daponte, Antonio; Caracò, Corrado; Chiofalo, Maria Grazia; Melucci, Maria Teresa; Calignano, Rosario; Tatangelo, Fabiana; Cochran, Alistair J; Castello, Giuseppe

    2003-06-01

    Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

  18. Tyrosinase-Cre-Mediated Deletion of the Autophagy Gene Atg7 Leads to Accumulation of the RPE65 Variant M450 in the Retinal Pigment Epithelium of C57BL/6 Mice

    Science.gov (United States)

    Sukseree, Supawadee; Chen, Ying-Ting; Laggner, Maria; Gruber, Florian; Petit, Valérie; Nagelreiter, Ionela-Mariana; Mlitz, Veronika; Rossiter, Heidemarie; Pollreisz, Andreas; Schmidt-Erfurth, Ursula; Larue, Lionel; Tschachler, Erwin

    2016-01-01

    Targeted gene knockout mouse models have helped to identify roles of autophagy in many tissues. Here, we investigated the retinal pigment epithelium (RPE) of Atg7f/f Tyr-Cre mice (on a C57BL/6 background), in which Cre recombinase is expressed under the control of the tyrosinase promoter to delete the autophagy gene Atg7. In line with pigment cell-directed blockade of autophagy, the RPE and the melanocytes of the choroid showed strong accumulation of the autophagy adaptor and substrate, sequestosome 1 (Sqstm1)/p62, relative to the levels in control mice. Immunofluorescence and Western blot analysis demonstrated that the RPE, but not the choroid melanocytes, of Atg7f/f Tyr-Cre mice also had strongly increased levels of retinoid isomerohydrolase RPE65, a pivotal enzyme for the maintenance of visual perception. In contrast to Sqstm1, genes involved in retinal regeneration, i.e. Lrat, Rdh5, Rgr, and Rpe65, were expressed at higher mRNA levels. Sequencing of the Rpe65 gene showed that Atg7f/f and Atg7f/f Tyr-Cre mice carry a point mutation (L450M) that is characteristic for the C57BL/6 mouse strain and reportedly causes enhanced degradation of the RPE65 protein by an as-yet unknown mechanism. These results suggest that the increased abundance of RPE65 M450 in the RPE of Atg7f/f Tyr-Cre mice is, at least partly, mediated by upregulation of Rpe65 transcription; however, our data are also compatible with the hypothesis that the RPE65 M450 protein is degraded by Atg7-dependent autophagy in Atg7f/f mice. Further studies in mice of different genetic backgrounds are necessary to determine the relative contributions of these mechanisms. PMID:27537685

  19. Recurrence of squamous cell lung carcinoma is associated with the co-presence of reactive lesions in tumor-adjacent bronchial epithelium.

    Science.gov (United States)

    Pankova, Olga V; Denisov, Evgeny V; Ponomaryova, Anastasia A; Gerashchenko, Tatiana S; Tuzikov, Sergey A; Perelmuter, Vladimir M

    2016-03-01

    Recurrences occur in 30 % of lung cancer patients after radical therapy; however, known prognostic factors are not always effective. In this study, we investigated whether the frequency of squamous non-small cell lung cancer (NSCLC) recurrence depends on the presence of reactive lesions in tumor-adjacent bronchial epithelium. Specimens of adjacent lung tissue from 104 patients with squamous NSCLC were used for the determination of basal cell hyperplasia (BCH) and squamous metaplasia (SM) and for the analysis of the expression of Ki-67, p53, Bcl-2, and CD138. We found that recurrence was observed in 36.7 % of patients with BCH combined with SM (BCH + SM+) in the same bronchus, compared with 1.8 % in patients with isolated BCH (BCH + SM-; odds ratio (OR) 31.26, 95 % confidence interval (CI) 3.77-258.60; p = 0.00002). The percentage of Ki-67-positive cells was significantly higher in BCH + SM+ than in BCH + SM- (34.9 vs. 18.3 %; effect size 2.86, 95 % CI 2.23-3.47; p = 0.003). P53 expression was also more significant in BCH + SM+ than in BCH + SM- (14.4 vs. 9.6 %; effect size 1.22, 95 % CI 0.69-1.76; p = 0.0008). In contrast, CD138 expression was lower in BCH + SM+ than in BCH + SM- (21.8 vs. 38.5 %; effect size -6.26, 95 % CI -7.31 to -5.22; p = 0.003). Based on our results, we concluded that the co-presence of reactive bronchial lesions is associated with the development of recurrent squamous NSCLC and may be a negative prognostic indicator. In addition, significant differences in Ki-67, p53, and CD138 expression exist between isolated BCH and BCH combined with SM that probably reflect part of biological differences, which could relate to the mechanism of lung cancer recurrence.

  20. Performance of a dermoscopy-based computer vision system for the diagnosis of pigmented skin lesions compared with visual evaluation by experienced dermatologists.

    Science.gov (United States)

    Zortea, Maciel; Schopf, Thomas R; Thon, Kevin; Geilhufe, Marc; Hindberg, Kristian; Kirchesch, Herbert; Møllersen, Kajsa; Schulz, Jörn; Skrøvseth, Stein Olav; Godtliebsen, Fred

    2014-01-01

    It is often difficult to differentiate early melanomas from benign melanocytic nevi even by expert dermatologists, and the task is even more challenging for primary care physicians untrained in dermatology and dermoscopy. A computer system can provide an objective and quantitative evaluation of skin lesions, reducing subjectivity in the diagnosis. Our objective is to make a low-cost computer aided diagnostic tool applicable in primary care based on a consumer grade camera with attached dermatoscope, and compare its performance to that of experienced dermatologists. We propose several new image-derived features computed from automatically segmented dermoscopic pictures. These are related to the asymmetry, color, border, geometry, and texture of skin lesions. The diagnostic accuracy of the system is compared with that of three dermatologists. With a data set of 206 skin lesions, 169 benign and 37 melanomas, the classifier was able to provide competitive sensitivity (86%) and specificity (52%) scores compared with the sensitivity (85%) and specificity (48%) of the most accurate dermatologist using only dermoscopic images. We show that simple statistical classifiers can be trained to provide a recommendation on whether a pigmented skin lesion requires biopsy to exclude skin cancer with a performance that is comparable to and exceeds that of experienced dermatologists. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Ai Ling Wang

    Full Text Available Age-related Macular Degeneration (AMD is a major cause of central vision loss in the elderly and smoking is a primary risk factor associated with the prevalence and incidence of AMD. To better understand the cellular and molecular bases for the association between smoking and AMD, we determined the effects of Benzo(aPyrene (B(aP, a toxic element in cigarette smoke, on cultured retinal pigment epithelia (RPE and we examined the RPE/choroid from mice exposed to chronic cigarette smoke. We measured: mitochondrial DNA (mtDNA damage, phagocytic activity, lysosomal enzymes, exosome markers and selected complement pathway components. In the presence of a non-cytotoxic dose of B(aP, there was extensive mtDNA damage but no nuclear DNA damage. RPE phagocytic activity was not altered but there were increased lysosomal activity, exocytotic activity and complement pathway components. Retinas from mice exposed to cigarette smoke contained markers for mtDNA damage, exosomes and complement pathway components surrounding Bruch's membrane. Markers for these processes are found in drusen from AMD patients. Thus, smoking may cause damage to mtDNA and increased degradative processes in the RPE. These altered cell biological processes in the RPE may contribute to the formation of drusen in individuals who are cigarette smokers and underlie susceptibility to genetic mutations associated with AMD.

  2. Oral postinflammatory pigmentation: an analysis of 7 cases.

    Science.gov (United States)

    Mergoni, Giovanni; Ergun, Sertan; Vescovi, Paolo; Mete, Özgür; Tanyeri, Hakkı; Meleti, Marco

    2011-01-01

    Oral postinflammatory pigmentation (OPP) is a discoloration of the oral mucosa caused by an excess of melanin production and deposition within the basal layer of the epithelium and connective tissue of areas affected by chronic inflammation. Therefore, it is mandatory to demonstrate the association with a previous or concomitant inflammatory process in the same area of oral mucosa. Clinically OPP appears as a localized or diffuse, black to brown pigmentation. OPP may persist for many years even though the disappearing of the pigmentation after the resolution of the inflammatory state has been reported. We reviewed retrospectively the medical records and, when performed, biopsy examinations of 7 cases of OPP. Four cases were associated with oral lichen planus, two cases with lichenoid lesions and one case with proliferative verrucous leukoplakia. Despite a possible high prevalence of OPP, only a few reports concerning diagnosis, etiopathogenesis and clinical manifestation have been published so far.

  3. Wnt信号通路在视网膜色素上皮发育中的作用%The roles of Wnt signaling pathway in the development of retinal pigment epithelium

    Institute of Scientific and Technical Information of China (English)

    殷秋菊; 赵娉婷; 杨春波; 李筱荣

    2014-01-01

    Wnt signaling plays important roles in embryonic development and cell differentiation, especially during central nervous system (CNS) development. At the early stage of eye development, retinal pigment epithelium (RPE) in the dorsal optic vesicle shows intensive Wnt/β-catenin signaling activity, which is critical for the development of neural retina and RPE. This review focuses on recent advances in the fields of Wnt signaling pathway, Wnt protein family and the relationship between Wnt signaling and RPE development and differentiation.%Wnt(wingless-type MMTV integration site family members)信号通路与细胞的发育分化密切相关,尤其对动物胚胎期中枢神经系统的发育至关重要。在眼的早期发育中,视泡背部视网膜色素上皮细胞(RPE)Wnt/βcatenin信号通路高度活跃,对神经视网膜及RPE的发育调控起重要作用。本文结合目前该领域研究进展,综合评述Wnt信号通路、Wnt蛋白家族以及Wnt信号通路与RPE发育的关系。

  4. 色素上皮衍生因子在肿瘤中的研究进展%The progression in the study of pigmented epithelium-derived factor in tumors

    Institute of Scientific and Technical Information of China (English)

    苏宏伟; 杨澄; 任慧文; 李宏伟

    2014-01-01

    色素上皮衍生因子(PEDF)作为丝氨酸蛋白酶抑制剂超家族成员,通过抑制内皮细胞的增殖和迁移、诱导相关的凋亡信号通路和增加肿瘤细胞分化程度,从而发挥抑制肿瘤发生、发展及其转移的生物学功能.研究表明,PEDF在骨骼的正常生理和病理过程发挥重要调节作用.PEDF为基础的免疫治疗方法可以成功的用于治疗骨肉瘤(OS),并极大抑制了OS的进展和控制肺部转移.%Pigmented epithelium-derived factor(PEDF),a member of the serine protease inhibitor family,could inhibit the occurrence,development and metastasis of tumors through controlling proliferation of endothelial cells,inducing apoptosis,and promoting the differentiation of tumor cells.Studies have showed that PEDF plays regulatory effects in physiological and pathological processes of the bone.PEDF-based immunotherapy could efficiently restrain the development of osteosarcoma (OS) and its lung metastusis.

  5. Translational read-through of the RP2 Arg120stop mutation in patient iPSC-derived retinal pigment epithelium cells

    Science.gov (United States)

    Schwarz, Nele; Carr, Amanda-Jayne; Lane, Amelia; Moeller, Fabian; Chen, Li Li; Aguilà, Mònica; Nommiste, Britta; Muthiah, Manickam N.; Kanuga, Naheed; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin; da Cruz, Lyndon; Coffey, Peter J.; Cheetham, Michael E.; Hardcastle, Alison J.

    2015-01-01

    Mutations in the RP2 gene lead to a severe form of X-linked retinitis pigmentosa. RP2 patients frequently present with nonsense mutations and no treatments are currently available to restore RP2 function. In this study, we reprogrammed fibroblasts from an RP2 patient carrying the nonsense mutation c.519C>T (p.R120X) into induced pluripotent stem cells (iPSC), and differentiated these cells into retinal pigment epithelial cells (RPE) to study the mechanisms of disease and test potential therapies. RP2 protein was undetectable in the RP2 R120X patient cells, suggesting a disease mechanism caused by complete lack of RP2 protein. The RP2 patient fibroblasts and iPSC-derived RPE cells showed phenotypic defects in IFT20 localization, Golgi cohesion and Gβ1 trafficking. These phenotypes were corrected by over-expressing GFP-tagged RP2. Using the translational read-through inducing drugs (TRIDs) G418 and PTC124 (Ataluren), we were able to restore up to 20% of endogenous, full-length RP2 protein in R120X cells. This level of restored RP2 was sufficient to reverse the cellular phenotypic defects observed in both the R120X patient fibroblasts and iPSC-RPE cells. This is the first proof-of-concept study to demonstrate successful read-through and restoration of RP2 function for the R120X nonsense mutation. The ability of the restored RP2 protein level to reverse the observed cellular phenotypes in cells lacking RP2 indicates that translational read-through could be clinically beneficial for patients. PMID:25292197

  6. αB crystallin is apically secreted within exosomes by polarized human retinal pigment epithelium and provides neuroprotection to adjacent cells.

    Directory of Open Access Journals (Sweden)

    Parameswaran G Sreekumar

    Full Text Available αB crystallin is a chaperone protein with anti-apoptotic and anti-inflammatory functions and has been identified as a biomarker in age-related macular degeneration. The purpose of this study was to determine whether αB crystallin is secreted from retinal pigment epithelial (RPE cells, the mechanism of this secretory pathway and to determine whether extracellular αB crystallin can be taken up by adjacent retinal cells and provide protection from oxidant stress. We used human RPE cells to establish that αB crystallin is secreted by a non-classical pathway that involves exosomes. Evidence for the release of exosomes by RPE and localization of αB crystallin within the exosomes was achieved by immunoblot, immunofluorescence, and electron microscopic analyses. Inhibition of lipid rafts or exosomes significantly reduced αB crystallin secretion, while inhibitors of classic secretory pathways had no effect. In highly polarized RPE monolayers, αB crystallin was selectively secreted towards the apical, photoreceptor-facing side. In support, confocal microscopy established that αB crystallin was localized predominantly in the apical compartment of RPE monolayers, where it co-localized in part with exosomal marker CD63. Severe oxidative stress resulted in barrier breakdown and release of αB crystallin to the basolateral side. In normal mouse retinal sections, αB crystallin was identified in the interphotoreceptor matrix. An increased uptake of exogenous αB crystallin and protection from apoptosis by inhibition of caspase 3 and PARP activation were observed in stressed RPE cultures. αB Crystallin was taken up by photoreceptors in mouse retinal explants exposed to oxidative stress. These results demonstrate an important role for αB crystallin in maintaining and facilitating a neuroprotective outer retinal environment and may also explain the accumulation of αB crystallin in extracellular sub-RPE deposits in the stressed microenvironment in age

  7. The 5HT1a receptor agonist 8-Oh DPAT induces protection from lipofuscin accumulation and oxidative stress in the retinal pigment epithelium.

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    Prajitha Thampi

    Full Text Available Age-related macular degeneration (AMD, a major cause of blindness in the elderly, is associated with oxidative stress, lipofuscin accumulation and retinal degeneration. The aim of this study was to determine if a 5-HT(1A receptor agonist can reduce lipofuscin accumulation, reduce oxidative damage and prevent retinal cell loss both in vitro and in vivo. Autophagy-derived and photoreceptor outer segment (POS-derived lipofuscin formation was assessed using FACS analysis and confocal microscopy in cultured retinal pigment epithelial (RPE cells in the presence or absence of the 5-HT(1A receptor agonist, 8-OH DPAT. 8-OH DPAT treatment resulted in a dose-dependent reduction in both autophagy- and POS-derived lipofuscin compared to control. Reduction in autophagy-induced lipofuscin was sustained for 4 weeks following removal of the drug. The ability of 8-OH DPAT to reduce oxidative damage following exposure to 200 µM H(2O(2 was assessed. 8-OH DPAT reduced superoxide generation and increased mitochondrial superoxide dismutase (MnSOD levels and the ratio of reduced glutathione to the oxidized form of glutathione in H(2O(2-treated cells compared to controls and protected against H(2O(2-initiated lipid peroxidation, nitrotyrosine levels and mitochondrial damage. SOD2 knockdown mice, which have an AMD-like phenotype, received daily subcutaneous injections of either saline, 0.5 or 5.0 mg/kg 8-OH DPAT and were evaluated at monthly intervals. Systemic administration of 8-OH DPAT improved the electroretinogram response in SOD2 knockdown eyes of mice compared to knockdown eyes receiving vehicle control. There was a significant increase in the ONL thickness in mice treated with 8-OH DPAT at 4 months past the time of MnSOD knockdown compared to untreated controls together with a 60% reduction in RPE lipofuscin. The data indicate that 5-HT(1A agonists can reduce lipofuscin accumulation and protect the retina from oxidative damage and mitochondrial dysfunction. 5-HT

  8. Bilateral lesions of suprachiasmatic nuclei affect circadian rhythms in (/sup 3/H)-thymidine incorporation into deoxyribonucleic acid in mouse intestinal tract, mitotic index of corneal epithelium, and serum corticosterone

    Energy Technology Data Exchange (ETDEWEB)

    Scheving, L.E.; Tsai, T.H.; Powell, E.W.; Pasley, J.N.; Halberg, F.; Dunn, J.

    1983-03-01

    Investigations into the role of the suprachiasmatic nuclei (SCN) in the coordination of circadian rhythms have presented differing results. Several reports have shown that ablation of the suprachiasmatic nuclei (SCNA) alters the phase and amplitude of rhythms but does not abolish them. The present study investigates the effect of SCNA on the rhythms in cell proliferation in various regions of the intestinal tract as measured by the incorporation of (/sup 3/H)-thymidine into deoxyribonucleic acid, in the mitotic activity of the corneal epithelium, and in serum corticosterone levels. The study involved mice with verified lesions of the SCN (six to 13 mice per time point) and control groups of both sham-operated and unoperated mice (seven of each per time point). The mice were killed in groups that represented seven time points over a single 24 hr span (3 hr intervals with the 0800 hr sampled both at start and end of the series). The tissues examined were the tongue, esophagus, gastric stomach, and colon for DNA synthesis, the corneal epithelium for mitotic index, and blood serum for corticosterone level. The most consistent result of SCNA was a phase advance in the rhythms in cell proliferation in the tongue, esophagus, gastric stomach, colon, and corneal epithelium. A reduction in rhythm amplitude occurred in the tongue, esophagus, and corneal epithelium; however, there was an amplitude increase for the stomach, colon, and serum corticosterone. The mesor (rhythm-adjusted mean) was increased by SCNA in all tissues except the corneal epithelium. These findings further support the role of the suprachiasmatic nuclear area in the control of rhythms in cell proliferation and corticosterone production, by acting as a ''phase-resetter'' and as a modulator of rhythm amplitude.

  9. Inhibition of Corneal Neovascularization with the Combination of Bevacizumab and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 (p-PEDF-SAINT-18 Vector in a Rat Corneal Experimental Angiogenesis Model

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    Ching-Hsein Chen

    2013-04-01

    Full Text Available Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups (Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μg of p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV. The bFGF and PEDF genes were successfully expressed as shown by western blot analysis, and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival.Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonalantibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeabilityproperties. In this study, we demonstrated that the combination of bevacizumaband plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and

  10. The complex interplay between ERK1/2, TGFβ/Smad, and Jagged/Notch signaling pathways in the regulation of epithelial-mesenchymal transition in retinal pigment epithelium cells.

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    Xiaoyun Chen

    Full Text Available Epithelial-mesenchymal transition (EMT of retinal pigment epithelium (RPE cells is a major pathologic change in the development of proliferative vitreoretinopathy (PVR, which leads to severe visual impairment. ERK1/2 pathway has been reported to play a key role in the carcinogenesis, cancer metastasis, and multiple fibrotic diseases. We hypothesized that ERK1/2 signaling could cross-interact with transforming growth factor β2 (TGFβ2/Smad and Notch signaling pathways in the regulation of EMT in RPE cells. Here, we demonstrated that ERK1/2 signaling was activated in TGFβ2-induced EMT in human RPE cells, while blockade of the canonical TGFβ2/Smad2/3 signaling with SB431542 could not inhibit TGFβ2-induced the activation of ERK1/2. Meanwhile, blockade of ERK1/2 signaling with a specific MEK/ERK1/2 inhibitor U0126 strongly prevented TGFβ2-induced the downregulation of P-cadherin, and the upregulation of α-SMA, collagen type IV, N-cadherin and fibronectin in RPE cells. In addition, we also identified that blockade of ERK1/2 signaling could inhibit not only the canonical TGFβ/Smad signaling, but also the Jagged/Notch pathway. Finally, we found that blockade of Notch pathway with a specific inhibitor DAPT could inhibit TGFβ2-induced the activation of ERK1/2 pathway conversely. Therefore, our study provides evidence that ERK1/2 signaling can cross-interact with the canonical TGFβ/Smad and the Jagged/Notch signaling pathways in RPE cells EMT. ERK1/2 inhibitor may have therapeutic value in the prevention and treatment of PVR and other fibrotic diseases.

  11. Bis-Retinoid A2E Induces an Increase of Basic Fibroblast Growth Factor via Inhibition of Extracellular Signal-Regulated Kinases 1/2 Pathway in Retinal Pigment Epithelium Cells and Facilitates Phagocytosis

    Science.gov (United States)

    Balmer, Delphine; Bapst-Wicht, Linda; Pyakurel, Aswin; Emery, Martine; Nanchen, Natacha; Bochet, Christian G.; Roduit, Raphael

    2017-01-01

    Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD. PMID:28298893

  12. Protocol for the MoleMate™ UK Trial: a randomised controlled trial of the MoleMate system in the management of pigmented skin lesions in primary care [ISRCTN 79932379

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    Wilson Edward CF

    2010-05-01

    Full Text Available Abstract Background Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. Differentiating melanomas from other pigmented lesions in primary care is challenging: currently, 95% of all lesions referred to a UK specialist are benign. The MoleMate system is a new diagnostic aid, incorporating a hand-held SIAscopy scanner with a primary care diagnostic algorithm. This trial tests the hypothesis that adding the MoleMate system to current best primary care practice will increase the proportion of appropriate referrals of suspicious pigmented lesions to secondary care compared with current best practice alone. Methods/design The MoleMate UK Trial is a primary care based multi-centre randomised controlled trial, with randomisation at patient level using a validated block randomisation method for two age groups (45 years and under; 46 years and over. We aim to recruit adult patients seen in general practice with a pigmented skin lesion that cannot immediately be diagnosed as benign and the patient reassured. The trial has a 'two parallel groups' design, comparing 'best practice' with 'best practice' plus the MoleMate system in the intervention group. The primary outcome is the positive predictive value (PPV of referral defined as the proportion of referred lesions seen by secondary care experts that are considered 'clinically significant' (i.e. biopsied or monitored. Secondary outcomes include: the sensitivity, specificity and negative predictive value (NPV of the decision not to refer; clinical outcomes (melanoma thickness, 5 year melanoma incidence and mortality; clinician outcomes (Index of Suspicion, confidence, learning effects; patient outcomes (satisfaction, general and cancer-specific worry, and cost-utility. Discussion The MoleMate UK Trial tests a new technology designed to improve the management of suspicious pigmented lesions in primary care

  13. Protective effect of genistein on human retinal pigment epithelium cell cultured in high glucose%金雀异黄素对高糖诱导的人RPE细胞损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    帅捷; 洪瑾; 袁志兰

    2007-01-01

    目的 探讨金雀异黄素(genistein,Gen)对高糖诱导的人视网膜色素上皮(retinal pigment epithelium,RPE)细胞的保护作用.方法 培养人RPE细胞,分别以Gen 0 μmol·L-1、50 μmol·L-1、100 μmol·L-1、200 μmol·L-1的药物浓度作用高糖(33 mmol·L-1)培养的RPE细胞48 h,噻唑蓝比色法检测细胞活性;流式细胞仪检测细胞周期;激光共聚焦显微镜检测细胞内活性氧(reactive oxygen species,ROS)水平;黄嘌呤氧化酶法测定细胞内超氧化物歧化酶(SOD)活性.结果 高糖组细胞活力(0.308±0.022)明显低于正常对照组(0.424±0.014)(P<0.01);高糖+Gen组细胞活力较高糖组升高(P<0.05),且随Gen浓度增大,细胞活力增加更明显.与正常对照组比较,高糖组细胞增殖受到抑制,被阻滞于S期和G2期;与高糖组比较,Gen可减轻高糖对细胞增殖的抑制作用.与正常对照组比较,高糖组细胞内ROS的产生明显增多;Gen以浓度依赖方式抑制高糖组RPE细胞内ROS的产生.与正常对照组(31.04±0.02)比较,高糖组SOD活性(12.32±0.02)显著降低(P<0.01);与高糖组比较,高糖+Gen组SOD活性随Gen浓度的增加而升高(均P<0.05).结论 Gen可保护和修复高糖诱导的人RPE细胞的损伤,其作用可能与抗氧化、增强SOD活性有关.

  14. In vitro culture and phagocytosis of human embryonic retinal pigment epithelium%人胚胎视网膜色素上皮细胞的体外培养和吞噬作用

    Institute of Scientific and Technical Information of China (English)

    靳晓亮; 徐国彤; 张文芳; 鲁建华

    2011-01-01

    Objective To analyze the culturing characteristics and phagocytosis of the retinal pigment epithelium (RPE) from human embryo, and to provide the cellular basis for the further research of RPE related diseases. Methods Fresh human embryonic eyeballs (13~15 weeks) were collected, and RPE cells were separated by mechanical and trypsin digestion after microdissec-tion. Human embryonic RPE phagocytosis of retinal outer segments was investigated by using immunofluorescence. Results After the human embryo had developed for 13~15 weeks, the RPE cells could be cultured in vitro according to standard culturing methods. Based on the growth curve, the RPE cells in generations 2~6 were collected for essays and showed the ability of phagocytosis afterwards. Conclusion The method of culturing human embryonic RPE cells is improved, and phagocytosis ability of human embryonic RPE cells is also proved in vitro according to this study.%目的 探讨人胚胎视网膜色素上皮(RPE)细胞分离培养的特性及其吞噬作用.方法 取发育至13~15周的新鲜人胚胎眼球,显微解剖后采用机械胰酶消化法分离培养RPE细胞,应用免疫荧光法观察人胚胎RPE细胞吞噬视网膜光感受细胞外节膜盘.结果 人胚胎发育至13~15周后,RPE细胞可应用标准的培养方法进行体外培养和传代.根据测定的人胚胎RPE细胞生长曲线,取2~6代细胞用于实验培养的人胚胎RPE细胞具备吞噬功能.结论 改进了人胚胎RPE细胞的培养方法,证明人胚胎RPE细胞在体外具有吞噬能力.

  15. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    Science.gov (United States)

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2016-09-08

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP. © 2016

  16. DRUGS CAUSING OROFACIAL PIGMENTATION: AN OVERVIEW OF LITERATURE

    OpenAIRE

    Shamimul Hasan; Nabeel Ishrat Khan; Osama Adeel Khan Sherwani; Shane Rafi; Ayesha Siddiqui

    2013-01-01

    The term “Oro-facial pigmentation” refers to a wide range of lesions or conditions featuring a change of color of Oro-facial tissues. Pigmentation of the Oro-facial tissues is seen in certain races or ethnic groups such as Indians, Africans and Europeans. Broadly classifying, Oro-facial pigmentation is divided into endogenous pigmentation and exogenous pigmentation. Endogenous pigmentation is due to pigments produced within the body. Exogenous pigmentation occurs when foreign bodies get impre...

  17. Definition of an automated Content-Based Image Retrieval (CBIR system for the comparison of dermoscopic images of pigmented skin lesions

    Directory of Open Access Journals (Sweden)

    Manganaro Mario

    2009-08-01

    Full Text Available Abstract Background New generations of image-based diagnostic machines are based on digital technologies for data acquisition; consequently, the diffusion of digital archiving systems for diagnostic exams preservation and cataloguing is rapidly increasing. To overcome the limits of current state of art text-based access methods, we have developed a novel content-based search engine for dermoscopic images to support clinical decision making. Methods To this end, we have enrolled, from 2004 to 2008, 3415 caucasian patients and collected 24804 dermoscopic images corresponding to 20491 pigmented lesions with known pathology. The images were acquired with a well defined dermoscopy system and stored to disk in 24-bit per pixel TIFF format using interactive software developed in C++, in order to create a digital archive. Results The analysis system of the images consists in the extraction of the low-level representative features which permits the retrieval of similar images in terms of colour and texture from the archive, by using a hierarchical multi-scale computation of the Bhattacharyya distance of all the database images representation with respect to the representation of user submitted (query. Conclusion The system is able to locate, retrieve and display dermoscopic images similar in appearance to one that is given as a query, using a set of primitive features not related to any specific diagnostic method able to visually characterize the image. Similar search engine could find possible usage in all sectors of diagnostic imaging, or digital signals, which could be supported by the information available in medical archives.

  18. 基因转染的虹膜色素上皮细胞移植后RCS鼠视网膜BDNF表达观察%Retinal BDNF expressions in RCS rats after transplantation of gene transfected iris pigment epithelium

    Institute of Scientific and Technical Information of China (English)

    张英瑜; 高朋芬; 杨丽霞

    2011-01-01

    目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因转染的虹膜色素上皮细胞(AAV-BDNF-IPE)移植入皇家外科学院(royal college of surgeons,RCS)大鼠视网膜下腔后,不同时期视网膜组织BDNF表达变化.方法 通过外路途径将BDNF基因转染的虹膜色素上皮细胞移植到RCS大鼠视网膜下腔,术后3、5、7、9、11周分别取RCS大鼠手术眼及对照组动物眼视网膜组织,用酶联免疫吸附法(Elisa)检测视网膜组织中BDNF的表达水平,比较分析这些数据.结果 对照组RCS大鼠出生后3周龄时视网膜组织中BDNF仍保持较高水平,其后迅速降低,其中3周龄组与其它周龄组比较,P<0.01;手术组RCS大鼠术时、术后3、5、7、9、11周各组间两两比较,BDNF表达无显著差异(P>0.05);出生后6周龄直到14周龄的不同时期,AAV-BDNF-IPE移植手术组RCS大鼠视网膜BDNF表达水平均明显高于对照组(其中6周龄组P<0.05,其它各周龄组P<0.01).结论 BDNF基因转染的虹膜色素上皮细胞在RCS大鼠视网膜下腔移植后,视网膜组织中BDNF可以持续稳定高水平表达,这为临床开发新的神经营养因子给药方式提供了实验依据.%Objective To investigate the retinal brain derived neurotrophic factor( BDNF) expressions in different phases of royal college of surgeons( RCS) rats after BDNF transfected iris pigment epithelium( AAV-BDNF-IPE) being transplanted into the subretinal space of RCS rat. Methods AAV-BDNF-IPEs were transplanted into the subretinal space of RCS rats. BDNF expressions in retinal tissue of intact RCS rats and surgery RCS rats were detected by enzyme linked immunosorbent assay ( Elisa) at 3 ,5 ,7 ,9and 11 weeks after surgery. Results BDNF expressions in retinal tissue of intact RCS rats were still high at postnatal 3w and were sharply decreased into low level later; retinal BDNF expression of intact RCS rats at postnatal 3w were much higher than those at other

  19. The inhibitory effect of pigment epithelium-derived factor on migration of gliomas%色素上皮细胞衍生因子与胶质瘤侵袭的相关性

    Institute of Scientific and Technical Information of China (English)

    张伎; 关明; 吕元

    2008-01-01

    目的 评价色素上皮细胞衍生因子(PEDF)对胶质瘤侵袭的抑制作用.方法 将PEDF(100 ng/ml)加入胶质瘤细胞U87中(U87PEDF),以未加PEDF蛋白的胶质瘤细胞作对照组(U87con),同时在U87PEDF中加入0.25μg/ml的促血管生成因子(VEGF,U87PEDF+VEGF).细胞迁徙实验检测PEDF抑制胶质瘤细胞侵袭性;实时荧光定量逆转录(RT)-PCR检测层粘连蛋白Laminin-8表达.结果 迁徙实验结果表明,对照组胶质瘤细胞穿透数明显多于PEDF处理组细胞,加入VEGF后,胶质瘤细胞迁徙率的抑制率仍减少38%;实时荧光定量RT-PCR结果显示,U87对照组 Laminin-8α4、β1、γlmRAN表达分别为(1.043±0.090)、(0.823±0.012)、(0.762±0.005)拷贝/μl,明显高于U87PEDF组[(0.633±0.004)、(0.442±0.005)、(0.424±0.002)拷贝/μl,P<0.05].结论 在VEGF存在的条件下,PEDF能有效抑制胶质瘤细胞的迁徙,表明其可能由下调Laminin-8基因的表达所致.%Objective To assess the impact of pigment epithelium-derived factor(PEDF) on the migration of the glioma cells.Methods PEDF(100 ng/ml)was added to U87 cells(U87PFDF),and VEGF of 0.25μg/ml was added to U87PEDF+VEGF while U87 cells as control(U87con).The cell migratory assav was used tbr evaluating its inhibitory migration rate of PEDF.Real time RT-PCR was used for evaluating the expression of Laminin-8 gene.Results The number of migratory cells was higher than those with added PEDF,and the inhibitory rate of migratory was 38% even in the presence of VEGF.Real time RT-PCR revealed that the mRNA expression levels of α4,β1,γl were(1.043±0.090),(0.823±0.012).(0.762±0.05) copy/μl,which were higher than those treated by PEDF(0.633±0.004),(0.442±0.005).(0.424±0.002)copy/μl,respectively (P<0.05).Conclusion PEDF could decrease the migmtory capacity of the glioma cells even in the presence of VEGF because of the regulation of Laminin-8 in part.

  20. Methods for culturing retinal pigment epithelial cells: a review of current protocols and future recommendations

    Directory of Open Access Journals (Sweden)

    Aaron H Fronk

    2016-07-01

    Full Text Available The retinal pigment epithelium is an important part of the vertebrate eye, particularly in studying the causes and possible treatment of age-related macular degeneration. The retinal pigment epithelium is difficult to access in vivo due to its location at the back of the eye, making experimentation with age-related macular degeneration treatments problematic. An alternative to in vivo experimentation is cultivating the retinal pigment epithelium in vitro, a practice that has been going on since the 1970s, providing a wide range of retinal pigment epithelial culture protocols, each producing cells and tissue of varying degrees of similarity to natural retinal pigment epithelium. The purpose of this review is to provide researchers with a ready list of retinal pigment epithelial protocols, their effects on cultured tissue, and their specific possible applications. Protocols using human and animal retinal pigment epithelium cells, derived from tissue or cell lines, are discussed, and recommendations for future researchers included.

  1. Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors: one year follow-up of a peripheral lesion

    Directory of Open Access Journals (Sweden)

    Rony Carlos Preti

    2015-06-01

    Full Text Available ABSTRACT This case report describes peripheral idiopathic polypoidal choroidal vasculopathy (IPCV with a collection of small aneurysmal dilations that masqueraded as choroidal tumors in an elderly patient. A 68-year-old African American woman was referred to us with a suspected diagnosis of asymptomatic vascular choroidal tumor and choroidal capillary hemangioma, affecting the temporal peripheral fundus. Upon examination, optical coherence tomography (OCT revealed two large hemorrhagic pigment epithelium detachments (PED, and indocyanine green angiography (ICG confirmed the diagnosis of IPCV. One year later, there was reduction in the hemorrhagic pigment epithelium detachments and the lesion took on a different appearance, resembling a choroidal osteoma. No treatment was necessary despite the presence of multiple polyps. IPCV is a rare condition that can resemble other choroidal diseases depending on the stage of presentation. OCT is the best tool to determine the characteristics of the lesions, and indocyanine green angiography should be used to confirm the diagnosis. Not all cases require treatment.

  2. A case of pigmented Bowen's disease*

    Science.gov (United States)

    Vivan, Márcia Maria; Hirata, Sérgio Henrique; do Nascimento, Liliane Santos; Enokihara, Milvia Maria Simões e Silva

    2017-01-01

    Pigmented Bowen's disease is a rare subtype of Bowen's disease. Clinically it presents as a slow-growing, well-defined, hyperpigmented plaque, and should be included as a differential diagnosis of other pigmented lesions. The authors describe a challenging case of pigmented Bowen's disease with non-diagnostic dermscopy findings. PMID:28225972

  3. Translocation of the retinal pigment epithelium and choroidal neovascularization induced by injecting Matrigel to subretinal space of rats%大鼠视网膜下注射Matrigel诱导视网膜色素上皮易位和脉络膜新生血管形成

    Institute of Scientific and Technical Information of China (English)

    汪振芳; 万鹏霞; 何丽文; 袁钊辉; 温容

    2007-01-01

    Objective To establish an animal model of sub-retinal pigment epithelium (sub-RPE)deposits,and to explore the pathological process of the transloeation of retinal pigment epithelium, choroidal neovascularization and the pathogenesis of age-related macular degeneration (AMD). Methods Matrigel was injected to the subretinal space of rats to create an amorphous deposit. Translocation of retinal pigment epithelium and choroidal neovascularization were observed. Results The subretinal deposit of Matrigel induced RPE translocation and therefore it became a sub-RPE deposit. The RPE mobilization required the presence of photoreceptors. Bruch's membrane devoid of RPE attachment became vulnerable to the invasion of new blood vessels from the choroid. Conclusions A novel model of sub-RPE deposit formation is established successfully. The presence of sub-RPE deposit is sufficient to induce choroidal neovascularization to penetrate Bruch's membrane and may cause the exudative form of AMD.%目的 制备视网膜色素上皮(RPE)下沉积物形成动物模型,并探讨其诱导视网膜色素上皮易位和脉络膜新牛血管(CNV)形成的病理过程以及年龄相关性黄斑变性(AMD)的发病机制.方法 将Matrigel基质胶注射于大鼠视网膜下形成视网膜下沉积物,观察视网膜色素上皮的迁移和脉络膜新生血管的形成.结果 Matrigel形成视网膜下沉积物后诱导RPE易位,而沉积物换位成为视网膜色素上皮层下沉积物.REP细胞的动员需要光感受器细胞的参与.缺乏色素上皮细胞贴附的Bruch膜易受脉络膜新生血管的侵袭.结论 建立了一个新的视网膜色素上皮层下沉积物形成的AMD动物模型.视网膜色素上皮层下沉积物足以导致CNV穿透Bruch膜,可能导致湿性AMD发生.

  4. Effects of extremely low frequency electromagnetic fields on human retinal pigment epithelium cells%极低频电磁场对体外培养人视网膜色素上皮细胞的影响

    Institute of Scientific and Technical Information of China (English)

    王洁; 朱煌; 杜尔罡

    2015-01-01

    Objective To investigate pathological changes in the molecules of human retinal pigment epithelium (hRPE) exposed to an extremely low frequency electromagnetic field (ELF-EMF),and study its possible significance in the occurrence and development of myopia.Methods In this experimental study,the experimental group was composed of hRPE exposed to 50 Hz electromagnetic fields; the untreated group was composed of hRPE without exposure.The changes in hRPE cell morphology were observed and cell proliferation in hRPE was measured by a CCK8 assay.The expressions of matrix metallo-proteinase-2 (MMP-2),tissue inhibitor of metalloproteinase 2 (TIMP-2),transforming growth factor-β2 (TGF-β2) and fibroblast growth factor 2 (FGF-2) mRNA in hRPE were detected by reverse transcription-polymerase chain reaction (RT-PCR).The concentrations of TGF-β2 and FGF-2 in the culture medium of hRPE were assayed by enzyme-linked immunosorbent assay (ELISA).The difference between the two group using independent t test.Results hRPE cell morphology changed,and the proliferation of hRPE was inhibited (t=-7.069,-3.652,-6.974,P< 0.05).The mRNA expressions of MMP-2,TIMP-2 and TGF-β2 were up-regulated significantly (t=10.562,6.277,4.940,P<0.01).However,the mRNA expression of FGF-2 was down-regulated significantly (t=-6.905,P<0.01).The results of ELISA indicated that after exposure to ELF-EMF,the expression of TGF-β2 in hRPE supernatant medium was up-regulated significantly (t=-4.079,P< 0.05).However,the expression of FGF-2 in hRPE supernatant medium was down-regulated (t=4.441,P<0.05).Conclusion ELF-EMF changed the proliferation of hRPE,and also changed the expressions of MMP-2,TIMP-2,TGF-β2 and FGF-2 mRNA in hRPE,which might induce the occurrence of myopia through pathological changes in the molecules of hRPE.%目的 研究极低频电磁场(ELF-EMF)作用下体外培养的人视网膜色素上皮细胞(hRPE)的分子病理改变,探讨其在近视发生发展

  5. 高级糖基化终末产物对人视网膜色素上皮细胞的作用机制研究%Advanced glycosylation end products and human retinal pigment epithelium cells

    Institute of Scientific and Technical Information of China (English)

    黄焱; 周敏; 郑卫东; 徐国兴

    2013-01-01

    目的 探讨高级糖基化终末产物(AGEs)对人视网膜色素上皮(RPE)细胞的作用机制.方法 原代培养人RPE细胞,在传代细胞生长状态良好的情况下,无血清的Dulbecco改良Eagle培养基同步化24 h,进行分组:(1)C组:BSA浓度为0.1 g/L,各作用24、48 h,分别为C1、C2组;(2)NC组:葡萄糖浓度为5.6 mmol/L,各作用24、48 h,分别为NC1、NC2组;(3)A组:AGEs浓度分别为0.1、0.2、0.4 g/L,各作用24、48 h,作用24 h依次为A1组、A2组、A3组,作用48 h依次为A4组、A5组、A6组.免疫组织化学检测AGEs受体(RAGE)、过氧化物酶体增生物激活受体γ辅助激活因子-1α(PGC-1α)和血管内皮生长因子(VEGF)蛋白的表达;激光共聚焦显微镜检测核因子-κB (NF-κB)的活化.通过图像分析软件IPP6.0和统计软件SPSS 17.0进行定量分析.结果 A组RPE细胞较C组和NC组RAGE、PGC-1α和VEGF蛋白的表达明显增加,且随着AGEs浓度的升高和刺激时间的延长而增加(F=294.5、228.3、241.5,P<0.05);随着AGEs浓度的升高和刺激时间的延长,NF-κB的活化增加.结论 AGEs的堆积可导致其受体RAGE在RPE细胞表达增加,并促进核转录共同激活因子PGC-1α蛋白的表达和NF-cB的活化,促进RPE细胞VEGF的分泌.%Objective To study the effect of advanced glycosylation end products (AGEs) on human retinal pigment epithelium (RPE) cells.Methods Human primary RPE cells were cultured in basal and different concentrations of AGEs with different times.The cells were divided into several groups as follows:group C (control):bovine serum albumin 0.1 g/L,24 hours (C1) and 48 hours (C2); group NC (normal control):basal culture medium with 5.6 mmol/L of glucose,24 hours (NC1) and 48 hours (NC2) ; group A (AGEs):0.1 g/L,24 hours and 48 hours,A1 and A4 ; 0.2 g/L,24 hours and 48 hours,A2 and A5 ; 0.4 g/L,24 hours and 48 hours,A3 and A6.Immunohistochemistry analysis was used to study the protein expression of receptor for AGEs (RAGE

  6. 色素上皮衍生因子抑制人肝癌裸鼠移植瘤生长%Pigment epithelium-derived factor gene therapy inhibits the growth of transplanted human hepatocellular carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    高云; 张伟; 赵亮; 王学浩

    2009-01-01

    目的 观察人色素上皮衍生因子(PEDF)对血管生成的抑制作用,探讨PEDF在肝癌基因治疗中的应用前景. 方法构建色素上皮衍生因子慢病毒表达质粒pLenti-PEDF,经293T细胞包装,收集病毒上清液,感染肝癌细胞株HepG2.收集各组细胞的条件培养基,通过Westernblot分析各组细胞PEDF的表达情况,并通过人脐静脉血管内皮细胞增殖及迁移试验研究其体外生物学活性.人肝癌细胞HepG2移植到裸鼠皮下,研究Lenti-PEDF病毒对肝癌移植瘤生长的抑制作用,逆转录聚合酶链反应检测肿瘤组织中PEDF mRNA表达.多组间均数比较采用单因素方差分析,组间两两比较采用LSD法.结果 限制性内切酶酶切分析和测序结果均表明成功构建了PEDF慢病毒表达载体,以293T细胞包装的重组慢病毒能够高效感染肝癌细胞,肝痛细胞感染重组慢病毒后可高效表达PEDF并分泌到培养上清液中.体外研究结果表明,重组PEDF可明显抑制人脐静脉血管内皮细胞的增殖及迁移,抑制率分别达29%和48%,与空白对照组相比,差异有统计学意义(P值均<0.01).Lenti-PEDF病毒能明显抑制人肝癌裸鼠皮下移植瘤的生长(P<0.01).瘤内注射Lenti-PEDF病毒21 d后,逆转录聚合酶链反应在肿瘤组织检测到PEDF mRNA的过表达.结论 本研究初步提示PEDF能有效遏制肿瘤的血管生成和肿瘤生长,为肝癌的基因治疗提供了一条新的思路.%Objectives To evaluate the antiangiogenic property of pigment epithelium-derived factor (PEDF) in heptocarcinoma cell lines and explore its possible application in the gene therapy of human hepa-tocellular carcinoma (HCC). Methods The gene encoding human PEDF was subcloned into lentiviral vector to generate the recombinant plasmid pLenti-PEDF. The plasmid pLenti-PEDF and two other packag-ing plasmids were cotransfected to 293T cells by calcium phosphate. Then HepG2 was infected with recom-binant lentivirus and the expression

  7. Laugier-hunziker pigmentation

    Directory of Open Access Journals (Sweden)

    Ajith C

    2005-01-01

    Full Text Available Laugier-Hunziker pigmentation (LHP is an acquired disorder of hypermelanosis characterized by mucocutaneous hyperpigmentation. LHP may resemble various disorders characterized by mucocutaneous pigmentation. A 58-year-old lady presented with progressively increasing number of variable sized, hyperpigmented macules over the lips, fingers, toes and nails. There was no family history of similar illness. Systemic examination and all relevant investigations were within normal limits. Histopathology of a skin lesion had features consistent with LHP. The diagnosis of LHP must be made only after relevant investigations to rule out any associated systemic involvement. This case further highlights that LHP is not restricted to European countries.

  8. 视网膜脱离外路显微手术中色素颗粒进入玻璃体临床观察%Clinical observation of intravitreal dispersion of retinal pigment epithelium cells during external approach microsurgery of retinal detachment

    Institute of Scientific and Technical Information of China (English)

    许大玲; 刘文; 霍鸣; 罗彤

    2008-01-01

    Objective It is a common phenomenon that a lot of pigmented debris disperses into vitreous cavity through retinal breaks during the cryotherapy or location of retinal breaks while the external approach microsurgery for rhegmatogenous retinal detachment (RRD) is performed.The study was designed for observing the surgical outcomes of this complication.Methods A consecutive thirty-eight patients (39eyes) with RRD,which were found intravitreal dispersion of retinal pigment epithelium cells during external approach mierosurgery of retinal detachment,were retrospectively analyzed.All of them were primary RRD and proliferative vitreoretinopathy (PVR) was classified equal to or under B.The numbers of average retinal breaks were 2.67.The size of the retinal break ranged from 1/7DD to 1.5 clock hour.The scleral buckling was performed in 11 eyes,and the circling and buckling in 28 eyes.Results The following-up times were 6 months at least.The retinal pigment epithelium cells of intravitreal dispersion gradually decreased and faded away.Retinal reattachment was achieved in 38 eyes (96.7%) after the primary surgery.A new retinal break was formed in one case and caused retinal redetachment.After vitreous surgery,this case got retinal reattachment.The final rate of reattachment was 100%.The excessive cryotherapy and severe PVR were not occurred.Conclusion As long as the holes or tears are closed effectively,the intravitreal dispersion of retinal pigment epithelium cells during external approach microsurgery of retinal detachment doesn't cause PVR develop or aggravate.The surgical outcomes are excellent.%目的 观察在视网膜脱离外路显微手术中做视网膜裂孔冷凝或定位时,色素颗粒从裂孔播散入玻璃体腔,对手术效果的影响.方法 回顾性统计分析视网膜脱离外路显微手术中有色素颗粒从裂孔涌人玻璃体腔的连续38例39只眼,均是初发裂孔性视网膜脱离患者,PVR分级为B级以下.平均每只眼裂孔数2.67

  9. Transport of protons and lactate in cultured human fetal retinal pigment epithelial cells

    DEFF Research Database (Denmark)

    Hamann, Steffen; Cour, Morten la; Ming Lui, Ge

    2000-01-01

    Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange......Electron microscopy, intracellular pH, monocarboxylate transport, pigment epithelium of eye, proton-lactate cotransport, retinal metabolism, sodium/proton exchange...

  10. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  11. Pink lesions.

    Science.gov (United States)

    Giacomel, Jason; Zalaudek, Iris

    2013-10-01

    Dermoscopy (dermatoscopy or surface microscopy) is an ancillary dermatologic tool that in experienced hands can improve the accuracy of diagnosis of a variety of benign and malignant pigmented skin tumors. The early and more accurate diagnosis of nonpigmented, or pink, tumors can also be assisted by dermoscopy. This review focuses on the dermoscopic diagnosis of pink lesions, with emphasis on blood vessel morphology and pattern. A 3-step algorithm is presented, which facilitates the timely and more accurate diagnosis of pink tumors and subsequently guides the management for such lesions.

  12. 色素内镜在上消化道早期癌及癌前病变的诊断价值%Diagnostic value for early cancer and precancerous lesions in the digestive tract under pigment endoscopy

    Institute of Scientific and Technical Information of China (English)

    陈函清; 潘文胜; 金冠福; 潘邦兴

    2012-01-01

    目的 研究色素内镜对上消化道早期癌及癌前病变的诊断价值.方法 将内镜下216例食管黏膜病变患者分为两组,染色组108例用Lugol氏液对食管黏膜染色,并对不染色和浅染色区进行病理活检;对照组108例食管黏膜患者进行单纯病理活检.将内镜下220例胃黏膜病变患者分为两组,染色组110例用靛胭脂一美兰染色后进行病理活检,对照组110例胃黏膜病变患者进行单纯病理活检.结果 食管染色组不染色或浅染色病例60例(55.6%),病理活检发现早期食管癌12例(11.1%),癌前病变6例(5.6%);胃染色组有69例(62.7%)不同程度染色,病理活检发现早期胃癌14例(12.7%),其中原位癌4例(3.6%),癌前病变9例(8.1%).发现早期癌及癌前病变与对照组的诊断率比较差异有显著性(P<0.01).结论 色素内镜有助于提高上消化道早期癌及癌前病变的诊断率及病理活检准确率,方法简便安全,值得基层医院推广.%[Objective] To study diagnostic value of early cancer and precancerous lesions in upper gastrointestinal under pigment endoscopy. [Methods] 216 cases of endoscopic esophageal mucosal lesions, staining group of 108 cases were treated with Lugol's solution staining of the esophageal mucosa, and non-staining and light staining zone biopsy; Control group, 108 cases of esophageal mucosa in patients with a simple biopsy. 220 cases of endo- scopic gastric mucosal lesions, indigo dyeing group of 110 cases with rouge - methylene blue staining and biopsy in the control group of 110 cases gastric mucosal lesions in patients with a simple biopsy. [Results] Esophagus didn't stain or stained pale group of 60 cases (55.6%), biopsy of 12 early esophageal cancer (11.1%), precancerous lesions in 6 patients (5.6%); Stomach stained group of 69 patients (62.7%) varying degrees of staining, biopsy detection of 14 early gastric cancer (12.7%), which carcinoma in situ in 4 cases, 9 cases of precancerous

  13. Acute Retinal Pigment Epitheliitis: Spectral Domain Optical Coherence Tomography, Fluorescein Angiography, and Autofluorescence Findings

    Directory of Open Access Journals (Sweden)

    Tuğba Aydoğan

    2015-01-01

    Full Text Available A 17-year-old presented with central and paracentral scotomas in his right eye for one week. There was no remarkable medical or ocular history. Blood analyses were within normal range. At presentation both eyes’ best-corrected visual acuities were 20/20. Slit-lamp examination result was normal. Fundus examination revealed yellow-white hypopigmented areas in the macula. Fluorescein angiography (FA showed hypofluorescence surrounded by ring of hyperfluorescence. Fundus autofluorescence (FAF was slightly increased. Spectral domain optical coherence tomography (SD-OCT showed disruption of IS/OS junction with expansion of abnormal hyperreflectivity from retinal pigment epithelium to the outer nuclear layer (ONL. One month later fundus examination showed disappearance of the lesions. FA revealed transmission hyperfluorescence. FAF showed increased autofluorescence and pigment clumping. Hyperreflective band in SD-OCT disappeared. Loss of photoreceptor segment layers was observed in some of the macular lesions. The diagnosis of acute retinal pigment epitheliitis can be challenging after disappearance of fundus findings. FA, FAF, and SD-OCT are important tests for diagnosis after resolution of the disease.

  14. Retinal Pigment Epithelium and Müller Progenitor Cell Interaction Increase Müller Progenitor Cell Expression of PDGFR and Ability to Induce Proliferative Vitreoretinopathy in a Rabbit Model

    Directory of Open Access Journals (Sweden)

    Gisela Velez

    2012-01-01

    Full Text Available Purpose. Proliferative vitreoretinopathy (PVR is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRα expression alter Müller cell pathogenicity. Methods. Human MIO-M1 Müller progenitor (MPC and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα (MIO-M1α was generated, and tested in a rabbit model for its ability to induce PVR. Results. The expression of PDGFRα and PDGFRβ was upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRα in the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model. Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRα and increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.

  15. Fine structure of the retinal pigment epithelium and cones of Antarctic fish Notohenia coriiceps Richardson in light and dark-conditions Ultraestrutra do epitélio pigmentar da retina e dos cones do peixe Antártico Notothenia coriiceps Richardson submetido à luz e ao escuro

    Directory of Open Access Journals (Sweden)

    Lucélia Donatti

    2007-03-01

    Full Text Available The Antarctic fish Notothenia coriiceps Richardson, 1844 lives in an environment of daily and annual photic variation and retina cells have to adjust morphologically to environmental luminosity. After seven day dark or seven day light acclimation of two groups of fish, retinas were extracted and processed for light and transmission electron microscopy. In seven day dark adapted, retina pigment epithelium melanin granules were aggregated at the basal region of cells, and macrophages were seen adjacent to the apical microvilli, between the photoreceptors. In seven day light adapted epithelium, melanin granules were inside the apical microvilli of epithelial cells and macrophages were absent. The supranuclear region of cones adapted to seven day light had less electron dense cytoplasm, and an endoplasmic reticulum with broad tubules. The mitochondria in the internal segment of cones adapted to seven day light were larger, and less electron dense. The differences in the morphology of cones and pigment epithelial cells indicate that N. coriiceps has retinal structural adjustments presumably optimizing vision in different light conditions.O peixe Antártico Notothenia coriiceps Richardson, 1844 habita meios com variações fóticas diária e anual e as células da retina se adaptam morfologicamente a esta luminosidade ambiental. Dois grupos de peixes foram aclimatados durante sete dias à luz constante ou ao escuro constante. Após secção medular, as retinas foram extraídas e processadas para microscopia de luz e microscopia eletrônica de transmissão. No epitélio pigmentar da retina adaptado sete dias ao escuro, os pigmentos de melanina agregam-se na base coroidal das células epiteliais pigmentares e macrófagos são encontrados no interior do processos apicais entre as células fotorreceptoras. No epitélio adaptado sete dias à luz os pigmentos de melanina se dispõem ao longo das projeções apicais das células epiteliais pigmentares e os

  16. Lesiones pigmentadas buco-faciales más frecuentes: Estudio clínico y correlación histopatológica The most frequent buccofacial pigmented injuries: Clinical study and histopathological correlation

    Directory of Open Access Journals (Sweden)

    Rafael Delgado Fernández

    2005-08-01

    Full Text Available Las lesiones pigmentadas de la piel y la mucosa bucal constituyen alteraciones que aparecen frecuentemente en la clínica estomatológica; por sus características y las diferentes formas de presentarse, su diagnóstico clínico con frecuencia discrepa del estudio morfológico. Por la importancia clínica de algunas de estas lesiones, nos propusimos hacer un estudio retrospectivo desde el punto de vista clínico y morfológico en 6 años (1998-2003, en los archivos de biopsias del Departamento de Patología de la Facultad de Estomatología. La búsqueda estuvo dirigida a aquellas solicitudes de biopsias sobre lesiones pigmentadas buco-faciales con su correspondiente informe histopatológico, con el propósito de determinar algunos parámetros clínicos como edad, sexo, localización y la correlación de diagnóstico clínico histopatológico. Se seleccionó un total de 155 biopsias de pacientes afectados. Los resultados indicaron que las lesiones que predominaron en los diagnósticos fueron las siguientes: los nevus (de localización cutánea, la pigmentación exógena, el léntigo y el melanoma, con una distribución del 65,2 %, 29 %, 4,5 % y 1,3 %, respectivamente. El sexo femenino fue el más afectado en cada una de las entidades. La presentación según grupos de edades fue variable, se observó que los nevus y el léntigo fueron más frecuentes en los jóvenes, entre los 30 y 39 años de edad (25,7 y 28,6 %, respectivamente, mientras que las pigmentaciones exógenas fueron más frecuentes en pacientes mayores de 60 años (26,7% en la cavidad bucal. Se estableció una correlación clínico-histopatológica, y de esta forma se comprobó el diagnóstico clínico o se rectificó este en cada uno de los casos estudiados.The pigmented injuries of the skin and oral mucosa are alterations that appear commonly at the dental clinic Due to their characteristics and different forms of presentation, their clinical diagnosis usually differs from the

  17. Skin Pigmentation Disorders

    Science.gov (United States)

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  18. Pseudoephedrine may cause "pigmenting" fixed drug eruption.

    Science.gov (United States)

    Ozkaya, Esen; Elinç-Aslan, Meryem Sevinç

    2011-05-01

    Fixed drug eruption (FDE) is a distinctive drug eruption characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. Two different clinical forms have been described: the common classic pigmenting form and the rare nonpigmenting form. Nonpigmenting FDE is mainly characterized by symmetrical large erythematous plaques and the dermal histopathologic reaction pattern. Pseudoephedrine is known as the major inducer of nonpigmenting FDE. Pigmenting FDE from pseudoephedrine has not been reported previously. Here, the first case of pseudoephedrine-induced pigmenting FDE is reported, showing the characteristic features of classic pigmenting FDE such as asymmetry, normal-sized lesions, and the epidermodermal histopathologic reaction pattern. Moreover, a positive occlusive patch-test reaction to pseudoephedrine could be demonstrated on postlesional FDE skin for the first time.

  19. Monascus pigments.

    Science.gov (United States)

    Feng, Yanli; Shao, Yanchun; Chen, Fusheng

    2012-12-01

    Monascus pigments (MPs) as natural food colorants have been widely utilized in food industries in the world, especially in China and Japan. Moreover, MPs possess a range of biological activities, such as anti-mutagenic and anticancer properties, antimicrobial activities, potential anti-obesity activities, and so on. So, in the past two decades, more and more attention has been paid to MPs. Up to now, more than 50 MPs have been identified and studied. However, there have been some reviews about red fermented rice and the secondary metabolites produced by Monascus, but no monograph or review of MPs has been published. This review covers the categories and structures, biosynthetic pathway, production, properties, detection methods, functions, and molecular biology of MPs.

  20. Fluorescence and reflectance properties of hemoglobin-pigmented skin disorders

    Science.gov (United States)

    Troyanova, P.; Borisova, E.; Avramov, L.

    2007-06-01

    There has been growing interest in clinical application of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue, including skin pathologies. Pigmented cutaneous lesions diagnosis plays important role in clinical practice, as malignant melanoma, which is characterized with greatest mortality from all skin cancer types, must be carefully discriminated form other colorized pathologies. The goals of this work were investigation of cutaneous hemoglobin-pigmented lesions (heamangioma, angiokeratoma, and fibroma) by the methods of LIAFS and RS. Spectra from healthy skin areas near to the lesion were detected to be used posteriori in analysis. Fluorescence and reflectance of cutaneous hemoglobin-pigmented lesions are used to develop criterion for differentiation from other pigmented pathologies. Origins of the spectral features obtained are discussed and determination of lesion types is achieved using selected spectral features. The spectral results, obtained were used to develop multispectral diagnostic algorithms based on the most prominent spectral features from the fluorescence and reflectance spectra of the lesions investigated. In comparison between normal skin and different cutaneous lesion types and between lesion types themselves sensitivities and specificities higher than 90 % were achieved. These results show a perspective possibility to differentiate hemoglobin-pigmented lesions from other pigmented pathologies using non-invasive and real time discrimination procedure.

  1. Bilateral pigmented villonodular synovitis of the knee

    Science.gov (United States)

    Shah, Samir H.; Porrino, Jack A.; Green, John R.; Chew, Felix S.

    2015-01-01

    Pigmented villonodular synovitis is a disorder resulting in a villous, nodular, or villonodular proliferation of the synovium, with pigmentation related to the presence of hemosiderin. These lesions are almost exclusively benign with rare reports of malignancy. Pigmented villonodular synovitis can occur in a variety of joints and at any age but most often occurs within the knee in the young adult. Pigmented villonodular synovitis is a rare disease entity, and bilateral synchronous or metachronous involvement of a joint is even more uncommon, with few reports previously described in the literature. We present a case of pigmented villonodular synovitis involving both the right and left knee in the same patient, with radiographic imaging, magnetic resonance imaging, photograph and video intraoperative imaging, and pathologic correlation. PMID:26649121

  2. Bilateral pigmented villonodular synovitis of the knee

    Directory of Open Access Journals (Sweden)

    Samir H. Shah

    2015-12-01

    Full Text Available Pigmented villonodular synovitis is a disorder resulting in a villous, nodular, or villonodular proliferation of the synovium, with pigmentation related to the presence of hemosiderin. These lesions are almost exclusively benign with rare reports of malignancy. Pigmented villonodular synovitis can occur in a variety of joints and at any age but most often occurs within the knee in the young adult. Pigmented villonodular synovitis is a rare disease entity, and bilateral synchronous or metachronous involvement of a joint is even more uncommon, with few reports previously described in the literature. We present a case of pigmented villonodular synovitis involving both the right and left knee in the same patient, with radiographic imaging, magnetic resonance imaging, photograph and video intraoperative imaging, and pathologic correlation.

  3. Depression of Intraocular Pressure Following Inactivation of Connexin43 in the Nonpigmented Epithelium of the Ciliary Body

    Science.gov (United States)

    Calera, Mónica R.; Wang, Zhao; Sanchez-Olea, Roberto; Paul, David L.; Civan, Mortimer M.; Goodenough, Daniel A.

    2010-01-01

    Purpose Conditional inactivation of connexin43 (Cx43) in the pigmented epithelium of the mouse eye results in a reduction in aqueous humor production and complete loss of the vitreous chamber. It was proposed that gap junctions between pigmented and nonpigmented epithelia of the ciliary body are critical for the production of the aqueous humor. To form such junctions, Cx43 in the pigmented epithelium must interact with connexin(s) present in the adjacent cells of the nonpigmented epithelium. The importance of Cx43 expression in the nonpigmented epithelium for the establishment of gap junctions and the regulation of intraocular pressure was tested. Methods To inactivate Cx43 in the nonpigmented epithelium of the mouse eye, a mouse line was crossed with a floxed Cx43 locus (Cx43flox/flox) and a transgenic mouse line expressing cre recombinase under the control of the Pax6α promoter. General eye structure was evaluated by light microscopy, gap junctions were analyzed by electron microscopy, and intraocular pressure was directly assessed with micropipettes. Results In Pax6α-cre/Cx43flox/flox mice, Cx43 was partially inactivated in the nonpigmented epithelium of the ciliary body and iris. Animals developed dilatations between the pigmented and nonpigmented epithelia and displayed a significant reduction in intraocular pressure. However, gap junctions between the ciliary epithelial layers were decreased but not eliminated. Conclusions Cx43 expression in the nonpigmented epithelium of the ciliary body contributes to the formation of gap junctions with the cells of the pigmented epithelium. These gap junctions play a critical role in maintaining the physical integrity of the ciliary body epithelium. Although the partial loss of Cx43 from the nonpigmented epithelium was correlated with a measurable drop in intraocular pressure, possible changes in Cx43 in the aqueous outflow pathway may provide an additional contribution to the observed phenotype. PMID:19168903

  4. Functional optical coherence tomography of pigmented lesions

    NARCIS (Netherlands)

    Wessels, R.; Bruin, de D.M.; Relyveld, G.N.; Faber, D.J.; Vincent, A.D.; Sanders, J.; Leeuwen, van T.G.; Ruers, T.J.M.

    2015-01-01

    Background Cutaneous melanomas are diagnosed worldwide in 231 130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of im

  5. Deer tick masquerading as pigmented conjunctival lesion

    Directory of Open Access Journals (Sweden)

    Robin K. Kuriakose

    2017-04-01

    Conclusions and importance: Despite the low risk for Lyme disease, which is endemic to the Adirondack region where the patient was affected, doxycycline was prescribed for prophylaxis. In any case of suspected tick penetration to the ocular surface, immediate ophthalmologic consultation and prompt removal via the method mentioned above is recommended, as well as attention paid to the Infectious Diseases Society of America guidelines regarding prophylaxis.

  6. Unusual extensive physiologic melanin pigmentation of the oral cavity: A clinical presentation

    Directory of Open Access Journals (Sweden)

    K Mallikarjuna

    2013-01-01

    Full Text Available Pigmented lesions are commonly found in the oral cavity. Oral pigmentations may be physiological or pathological in nature. It may represent as a localized anomaly of limited significance or the presentation of potentially life threatening multisystem disease. Oral pigmentation has a multifactorial etiology. Most of the oral pigmentations are physiologic. Evaluation of a patient with pigmented lesions should include a full medical and dental history, extraoral and intraoral examinations. In this article, we report a case of extensive physiologic pigmentation of the oral cavity in a 12 year old female patient, posing a diagnostic challenge.

  7. 水蛭渗滤液对凝血酶诱导的人视网膜色素上皮细胞周期的影响%The effects of leech percolate on cell dividing cycle of human retinal pigment epithelium cells induced by thrombin.

    Institute of Scientific and Technical Information of China (English)

    郑燕林; 左玉霞; 马素红

    2008-01-01

    Objective To investigate the effects of leech percolate on cell division cycle of culturedhuman retinal pigment epithelium (hRPE)cells induced by thrombin.Exploring mechanism of leech percolateon preventing and curing PVR.Methods (1)Human retinal pigment epithelium(hRPE)cells were cultured invitro with digest culture method. (2)The selected concentrations of leech percolate (128mg/ml,64mg/ml,32mg/ml,16mg/ml and 8mg/ml)were based on the previous experiments.With or without 0.5NIHU/mlthrombin, hRPE cells were treated with leech percolate by various concentrations for 24hrs, and the effects ofcell division cycle of leech percolate were studied with Flow Cytometer (FCM). (3)With or without0.5NIHU/ml thrombin, hRPE cells were treated with 64mg/ml leech percolate at different times(6hr, 12hr,24hrand 48hr), and the effects of cell division cycle of leech percolate were treated with FCM.Results (1)Therewas a general tendency that leech percolate of the selected concentrations arrested hRPE cells on G0/G1 phaseand 64mg/mi leech percolate inhibited 77.9% hRPE cells on G0/G1 phase and made hRPE cells on S phaseless especially. (2)During the period of 6hrs and 48hrs the longer the treat time of 64mg/ml leech percolate, themore the RPE cells arrested on G0/G1 phase.Conclusion The results approve leech percolate can inhibitproliferation of human RPE cells cultured in vitro.Its mechanism may be that leech percolate could act on celldivision cycle and arrest RPE cells on G0/G1 phase to make proliferation power of hRPE cells lower.%目的 研究水蛭渗滤液对凝血酶诱导的人视网膜色素上皮细胞周期的影响,从而探讨中药水蛭用于防治PVR的作用机制.方法 (1)采用消化培养法,对人视网膜色素上皮细胞进行体外传代培养. (2)在前期实验基础上选择128mg/ml、64mg/ml、32mg/ml、16mg/ml、8mg/ml浓度的水蛭渗滤液,用流式细胞仪测定细胞周期,观察水蛭渗滤液单独或与0.5NIHU/ml凝血酶共同作用

  8. [Regeneration of airway epithelium].

    Science.gov (United States)

    Adam, D; Perotin, J-M; Lebargy, F; Birembaut, P; Deslée, G; Coraux, C

    2014-04-01

    Epithelial regeneration is a complex process. It can lead to the remodeling of the airway epithelium as in asthma, COPD or cystic fibrosis. The development of in vivo and in vitro models has allowed the analysis of remodeling mechanisms and showed the role of components of extracellular matrix, proteases, cytokines and growth factors. Airway epithelial progenitors and stems cells have been studied in these models. However, their identification remains difficult. Identification and characterization of airway epithelial progenitor/stem-cells, and a better knowledge of the regeneration process may allow the development of new therapeutic strategies for airway epithelial reconstitution. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  9. 芪参益气滴丸对糖尿病大鼠视网膜血管内皮生长因子和色素上皮衍生因子表达的影响%Influence of Qishenyiqi Gutta Pills on expression of vascular endothelial growth factor and pigment epithelium derived factor in retina of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    苑维; 金明; 邓辉; 潘琳; 刘海丹

    2013-01-01

    目的:观察芪参益气滴丸对糖尿病大鼠视网膜血管内皮生长因子(VEGF)和色素上皮衍生因子(PEDF)及其mRNA表达的影响.方法:70只SD大鼠以链脲佐菌素(65mg/kg)诱导糖尿病大鼠模型,成模后随机分成模型组、对照组和芪参益气滴丸组.设正常组12只.10个月后用免疫组织化学方法检测各组视网膜VEGF和PEDF表达水平,逆转录-聚合酶链式反应检测VEGFmRNA和PEDFmRNA表达水平.结果:糖尿病大鼠视网膜VEGF及其mRNA表达较正常组显著增强(P<0.01),PEDF及其mRNA表达较正常组显著降低(P<0.01).对照组和芪参益气滴丸组视网膜VEGF及其mRNA表达较模型组降低,PEDF及其mRNA表达较模型组显著增加(P<0.01).结论:芪参益气滴丸可通过降低视网膜VEGF及其mRNA的表达、增加PEDF及其mRNA表达延缓糖尿病视网膜病变进展.%Objective:To discuss the influence of QiShenYiQi Gutta Pills (QGP)on expression of vascular en-dothelial growth factor (VEGF) .pigment epithelium derived factor (PEDF)and mRNA expression of VEGF and PEDF in rats with diabetic retinopathy.MethodS;The diabetic rat model was established by one-time injection of streptozotozin(STZ,65mg/kg).All SD rats(n=82)were randomly divided into the normal group,model group, control group and QGP group.After 10 months,the expression of VEGF and PEDF was detected by immuno-histochemistry method ,VEGFmRNA and PEDFmRNA were examined by reverse transcription-polymerase chain reaction(RT-PCR).Results:The expression of VEGF and VEGFmRNA in model group was higher than that in the normal group (P<0.01).The expression of PEDF and PEDFmRNA in model group was lower than the normal group (P<0.01).The expression of VEGF and VEGFmRNA in QGP group was lower than that in the model group (P<0.01).The expression of PEDF and PEDFmRNA in QGP group was higher than the model group (P<0.01).Conclusion;QGP can delay the development of diabetic retinopathy in rats through decreasing the expression

  10. Retinal Pigment Epithelial Features in Central Serous Chorioretinopathy Identified by Polarization-Sensitive Optical Coherence Tomography.

    Science.gov (United States)

    Roberts, Philipp; Baumann, Bernhard; Lammer, Jan; Gerendas, Bianca; Kroisamer, Julia; Bühl, Wolf; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula; Sacu, Stefan

    2016-04-01

    To determine the subclinical RPE lesions detected by tissue selective polarization-sensitive optical coherence tomography (PS-OCT) in eyes with central serous chorioretinopathy (CSC) and to compare PS-OCT findings to current imaging standards. In this prospective observational case series, individuals with unilateral or bilateral active CSC were imaged using PS-OCT at baseline and after resolution of serous retinal detachment. Features seen on PS-OCT were compared with corresponding lesions as seen on conventional, intensity-based spectral-domain OCT (SD-OCT), fluorescein angiography, and indocyanine green angiography (ICGA). Features of RPE evaluated by PS-OCT were as follows: area and volume of pigment epithelium detachment (PED), presence of RPE aggregations, RPE skip lesions, RPE thickening, and RPE atrophy. Twenty-five study eyes and 23 fellow eyes of 25 participants (2 women, 23 men; mean age ± standard deviation = 40.5 ± 7.4 years) were included and followed for 6.1 ± 3 months. Study eyes and fellow eyes with recurrent CSC showed more RPE abnormalities in PS-OCT than eyes with acute CSC, which correlated well with lesions in ICGA. Closure of the leakage site was observed only in eight (32%) eyes after resolution of subretinal fluid (SRF). All study eyes showed widespread RPE aggregates and 23 (92%) eyes showed RPE skip lesions after resolution of SRF. Features of RPE indicative of previous episodes of CSC detected by PS-OCT correspond well to choroidal lesions in ICGA. In addition, noninvasive PS-OCT imaging enables detection of RPE microrips and aggregations invisible to clinical examination or SD-OCT, thus providing valuable information about disease processes in vivo.

  11. Pigmented Villonodular Synovitis (PVNS)

    Science.gov (United States)

    ... OverviewWhat is pigmented villonodular synovitis?Pigmented villonodular synovitis (PVNS) is a joint problem that usually affects the ... ankle, elbow, hand or foot.When you have PVNS, the lining of a joint becomes swollen and ...

  12. Neovascularisation by tattoo pigment

    Directory of Open Access Journals (Sweden)

    Abdul Razack E

    1991-01-01

    Full Text Available Split skin grafting for the removal of a tattoo resulted in the appearance of pigmented papules in the periphery of the grafted skin as well as distal to it on the normal skin. Histologically they showed large vascular laminae containing red blood corpuscles and pigment deposits, a hitherto not documented complication of tattoo pigment.

  13. Overview of plant pigments

    Science.gov (United States)

    Chlorophylls, carotenoids, flavonoids and betalains are four major classes of biological pigments produced in plants. Chlorophylls are the primary pigments responsible for plant green and photosynthesis. The other three are accessary pigments and secondary metabolites that yield non-green colors and...

  14. Late-onset necrotizing scleritis due to pigmented mycetoma (dematiaceous fungi) in 2 cases.

    Science.gov (United States)

    Reddy, Jagadesh C; Rapuano, Christopher J; Eagle, Ralph C; Shields, Carol L; Shields, Jerry A

    2013-04-01

    To describe the atypical presentation of fungal infection and necrotizing scleritis, the potential role of histopathology in the diagnosis, and surgical excision in the management. Retrospective interventional case series. Two patients presented with a pigmented conjunctival mass, one resembling necrotizing scleritis with uveal prolapse and the other resembling a pigmented ocular surface tumor, both after excision of nasal pterygium, 12 and 50 years previously, respectively. The pigmented lesion was 2 × 1.5 mm in each case, both situated on the bulbar surface 2 mm from the nasal limbus. After surgical excision, each lesion histopathologically displayed fungal filaments (pigmented dematiaceous fungi). Pigmented mycetoma (dematiaceous fungi) can simulate uveal tissue prolapse, pigmented foreign body, or pigmented epibulbar tumors, particularly melanoma. Surgical excision of the entire lesion is effective for management.

  15. Assessing burn depth in tattooed burn lesions with LASCA Imaging.

    Science.gov (United States)

    Krezdorn, N; Limbourg, A; Paprottka, F J; Könneker; Ipaktchi, R; Vogt, P M

    2016-09-30

    Tattoos are on the rise, and so are patients with tattooed burn lesions. A proper assessment with regard to burn depth is often impeded by the tattoo dye. Laser speckle contrast analysis (LASCA) is a technique that evaluates burn lesions via relative perfusion analysis. We assessed the effect of tattoo skin pigmentation on LASCA perfusion imaging in a multicolour tattooed patient. Depth of burn lesions in multi-coloured tattooed and untattooed skin was assessed using LASCA. Relative perfusion was measured in perfusion units (PU) and compared to various pigment colours, then correlated with the clinical evaluation of the lesion. Superficial partial thickness burn (SPTB) lesions showed significantly elevated perfusion units (PU) compared to normal skin; deep partial thickness burns showed decreased PU levels. PU of various tattoo pigments to normal skin showed either significantly lower values (blue, red, pink) or significantly increased values (black) whereas orange and yellow pigment showed values comparable to normal skin. In SPTB, black and blue pigment showed reduced perfusion; yellow pigment was similar to normal SPTB burn. Deep partial thickness burn (DPTB) lesions in tattoos did not show significant differences to normal DPTB lesions for black, green and red. Tattoo pigments alter the results of perfusion patterns assessed with LASCA both in normal and burned skin. Yellow pigments do not seem to interfere with LASCA assessment. However proper determination of burn depth both in SPTB and DPTB by LASCA is limited by the heterogenic alterations of the various pigment colours.

  16. Graph-based pigment network detection in skin images

    Science.gov (United States)

    Sadeghi, M.; Razmara, M.; Ester, M.; Lee, T. K.; Atkins, M. S.

    2010-03-01

    Detecting pigmented network is a crucial step for melanoma diagnosis. In this paper, we present a novel graphbased pigment network detection method that can find and visualize round structures belonging to the pigment network. After finding sharp changes of the luminance image by an edge detection function, the resulting binary image is converted to a graph, and then all cyclic sub-graphs are detected. Theses cycles represent meshes that belong to the pigment network. Then, we create a new graph of the cyclic structures based on their distance. According to the density ratio of the new graph of the pigment network, the image is classified as "Absent" or "Present". Being Present means that a pigment network is detected in the skin lesion. Using this approach, we achieved an accuracy of 92.6% on five hundred unseen images.

  17. Dermoscopy Clues in Pigmented Bowen's Disease

    Directory of Open Access Journals (Sweden)

    Daniela Gutiérrez-Mendoza

    2010-01-01

    Full Text Available Pigmented tumors have similar clinical features that overlap and hamper diagnosis. Dermoscopy increases the diagnostic accuracy of doubtful melanocytic lesions and has been used as a noninvasive tool in the detection of pigmented lesions (PLs like melanoma, basal cell carcinoma, and pigmented Bowen's disease (pBD. Our objective was to show the dermoscopic features of 2 cases of pBD and compare with the findings reported in the literature. Two dermoscopic images of biopsy proven pBD were retrospectively analyzed for dermoscopic patterns. Both cases showed brown regular globules, structureless brown and blue pigmentation, glomerular vessels, hypopigmented regression-like areas, and keratosis. These findings were similar to the cases reported previously. The dermoscopic diagnosis of pBD is based on the absence of criteria for a melanocytic lesion in the presence of glomerular vessels, regular brown globules and keratosis. Although pBD is rare, it should be included in the differential diagnosis of PLs, especially melanoma.

  18. 小干扰RNA介导丝氨酸蛋白酶HtrA1沉默对光损伤人视网膜色素上皮细胞的影响%Influence of down-regulation of HtrA1 expression by small interfering RNA on light-injured human retinal pigment epithelium cells

    Institute of Scientific and Technical Information of China (English)

    余天; 邢怡桥; 陈长征

    2016-01-01

    Objective To observe the influence of down-regulation of HtrA1 expression by small interfering RNA on light-injured human retinal pigment epithelium (RPE) cells.Methods Cultured human RPE cells(8th-12th generations)were exposed to the blue light at the intensity of (2000 ± 500) Lux for 6 hours to establish the light injured model.Light injured cells were divided into HtrA1 siRNA group,negative control group and blank control group.HtrA1 siRNA group and negative control group were transfected with HtrA1 siRNA and control siRNA respectively.The proliferation of cells was assayed by CCK-8 method.Transwell test was used to detect the invasion ability of these three groups.Flow cytometry was used to detect the cell cycle and apoptosis.The expression of HtrA1 and vascular endothelial growth factor (VEGF)-A was detected by real time-polymerase chain reaction and Western blot respectively.Results The mRNA and protein level of HtrA1 in the light injured cells increased significantly compared to that in normal RPE cells (t=17.62,15.09;P<0.05).Compared with negative control group and blank control group,the knockdown of HtrA1 in HtrA1 siRNA group was associated with reduced cellular proliferation (t=6.37,4.52),migration (t =9.56,12.13),apoptosis (t =23.37,29.08) and decreased mRNA (t=17.36,11.32,7.29,4.05) and protein levels (t=12.02,15.28,4.98,6.24) of HtrA1 and VEGF-A.Cells of HtrA1 siRNA group mainly remained in G0/G1 phase,the difference was statistically significant (t=6.24,4.93;P <0.05).Conclusion Knockdown of HtrA1 gene may reduce the proliferation,migration capability and apoptosis of light-injured RPE cells,and decrease the expression of VEGF-A.%目的 观察丝氨酸蛋白酶HtrA1沉默对光损伤人视网膜色素上皮(RPE)细胞的影响.方法 体外培养人RPE细胞,取第8~12代生长良好的传代细胞用于实验.将细胞分为正常对照组、光损伤模型组.采用波长400 nm的蓝色节能灯以(2000±500) Lux持续光照RPE细胞6h建立

  19. The effects of anti-VEGF drugs on the retinal pigment epithelium and inner segment after intravitreal injection in the monkeys%猴眼玻璃体腔内注射抗VEGF药物对视网膜色素上皮层和光感受器内节VEGF含量的影响

    Institute of Scientific and Technical Information of China (English)

    苏楠; 李付广; Ulrich Schraermeyer

    2016-01-01

    目的::研究比较抗血管内皮生长因子( VEGF )药物(贝伐单抗、雷珠单抗、阿柏西晋)行猴眼玻璃体腔内注射后对视网膜色素上皮层和眼内节VEGF的作用效果。方法:选取14只健康猕猴,4只双眼注射贝伐单抗,4只双眼注射雷珠单抗,4只双眼注射阿柏西晋,每种注射药物的4只猴双眼分别于注射药物后第一天和第七天分别摘除2只猴的眼球,剩余2只未注射任何药物猴的双眼作为对照。所有摘除后的眼球福尔马林固定,石蜡包埋,切片后给予抗 VEGF 抗体,用光学显微镜观察,经 Image-Pro Plus软件处理图片,用JMP10.0进行统计学分析。结果:这三种药物均能降低视网膜色素上皮( RPE)和光感受器內节( inner segment)的VEGF水平,贝伐单抗作用在三种药物中作用最强,雷珠单抗在注射后第一天与阿柏西晋注射后第一天相比,雷珠单抗作用较强,但二者在注射后第七天,作用基本相似。结论:这三种药物均能降低RPE和inner segment的VEGF水平。%• AIM: To compare the effects on the retina inner segment and retinal pigment epithelium ( RPE ) of intravitreally injecting bevacizumab, ranibizumab and aflibercept into monkey eyes.• METHODS: Fourteen healthy cynomolgus monkeys (Macaca fascicularis, aged 3-8y,10 males,4 females) were raised at the Covance Laboratories under standard conditions. The 14 monkeys were grouped into 4 groups. Three of the groups with 4 monkeys each were injected intravitreally with one of the drugs, either bevacizumab, ranibizumab or aflibercept, while the 4th group with 2 monkeys served as a negative control. On 1d and 7d of injection, 2 monkeys from each drug treatment group were sacrificed under general anaesthesia and the 4 eyes were enucleated. All the enucleated eyes were fixed in formalin, embedded in paraffin wax, cut into 4. 0 μm sections and deparaffinized according to standard procedures. Image-Pro Plus was used for all the photos to

  20. Slit2基因转染对人视网膜色素上皮细胞VEGF表达的影响及其作用机制%Effect of Slit2 gene transfection on vascular endothelial growth factor in retinal pigment epithelium cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    梅雨; 周希瑗

    2014-01-01

    目的:研究Slit2基因对人视网膜色素上皮(retinal pigment epithelium,RPE)细胞表达血管内皮生长因子(vascular endothelial growth factor,VEGF)的影响,并探讨丝裂原激活(mitogen-activated,MEK)/细胞外信号调节蛋白激酶(extracellular signal regulated protein kinase,ERK)和磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI3K)/丝氨酸苏氨酸蛋白激酶(serine-threonine kinase,AKT)这2条信号通路在此过程中的作用.方法:(1)体外培养人RPE细胞株RPE-19; (2)将腺病毒介导的Slit2(adenovirus-mediated Slit2,Ad-Slit2)转染RPE细胞,培养12、24 h及48 h;(3)转染前将MEK信号通路阻断剂PD98059、PI3K 信号通路阻断剂LY294002预处理RPE细胞1 h;(4)用real-time PCR及酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测VEGF的表达水平,用Western blot检测磷酸化ERK、磷酸化AKT的表达情况.结果:Slit2转染的RPE细胞后,real-time PCR结果显示不同时间之间VEGF mRNA表达有差别(F=12.789,P=0.018),组别和时间之间存在交互作用(F=13.375,P=0.017),不同组别有差别(F=16.855,P=0.015),在24 h与48 h,Ad-Slit2组高于空腺病毒组(P4 h=0.002,P48 h=0.018).ELISA结果显示不同时间之间VEGF蛋白表达有差别(F=24.886,P=0.000),组别和时间之间存在交互作用(F=23.524,P=0.000),不同组别有差别(F=28.250,P=0.006),在48 h,Ad-Slit2组高于空腺病毒组(P=0.003).Western blot结果可见p-ERK及p-AKT的蛋白表达水平增加,阻断剂PD98059及LY294002分别能降低ERK、AKT的磷酸化水平,并与Ad-Slit2组相比较,real-time PCR结果显示VEGF mRNA表达水平在不同时间有差别(F=32.202,P=0.000),组别和时间之间存在交互作用(F=8.372,P=0.006);不同组别存在差别(F=15.062,P=0.001),ELISA结果显示VEGF蛋白表达水平在不同时间之间有差别(F=90.703,P=0.000),组别和时间之间存在交互作用(F=4.968,P=0.005),不同组别存在差别(F=69.636,P=0.000).结论:PI3K/AKT以及MEK/ERK这

  1. 不同波长的光照射对视网膜色素上皮细胞生长及其分泌生长因子的影响%Effects of different wave-length lights on proliferation and secretion of growth factors in human retinal pigment epithelium cells

    Institute of Scientific and Technical Information of China (English)

    郑晓汾; 康玉国; 褚仁远

    2011-01-01

    异均有统计学意义(P<0.05)。RT-PCR结果显示,不同波长光照射后RPE细胞中HGF mRNA的表达水平不同,蓝光下培养的RPE细胞HGF mRNA表达量最少,白光组、红光组和蓝光组HGF mRNA的表达量(A490)与对照组比较差异均有统计学意义( P<0.05)。透射电子显微镜下红光组、白光组人胚RPE细胞与对照组相比超微结构均无明显变化,但蓝光组RPE细胞核染色质稀疏变淡,细胞器减少,细胞界膜不清或消失。结论不同波长的光照射可影响人RPE细胞的增生及其分泌HGF、bFGF和TGF-β的功能,提示近视的形成可能与不同波长的光相互作用有关。%Background The study of myopia development is always the hotspot worldwide. Recently,scientist found that some growth factor secreted by retinal nerve epithelium cells and retinal pigment epithelium(RPE)cells are associated with the development of myopia. Whenever, the absorption of RPE cells to different wave-length lights is different. ObjectiveThis study was to investigate the effects of different wave-lengths lights on the proliferation of human RPE cells, and explore the influence of different wave-lengths lights on RPE cells secreting hepatocyte growth factor(HGF) ,basic fibroblast growth factor(bFGF) and transforming growth factor-β(TGF-β).Methods The fourth to fifth passages of human embryonic RPE cells were exposed to blue light( λ =480 nm),red light( λ =775 nm) and white light. The cells of control group were harvested in normal condition. The proliferation and growth of RPE cells were assayed by MTT,and the ultrastructure of cells was examined under the transmission electron microscopy at 48 hours after light exposure of RPE cells. Enzyme linked immunosorbent assay(ELISA) was adopted to determine the concentrations of HGF,bFGF and TGF-β in the culture medium in 12,24,48,72 hours. The expression of HGF mRNA in RPE cells was detected by RT-PCR. This study was approved by Ethic committee of Fudan University. Results

  2. Lesiones pigmentadas buco-faciales más frecuentes: Estudio clínico y correlación histopatológica The most frequent buccofacial pigmented injuries: Clinical study and histopathological correlation

    OpenAIRE

    Rafael Delgado Fernández; Rosa María Segismundo Rodríguez; Katia Barceló López

    2005-01-01

    Las lesiones pigmentadas de la piel y la mucosa bucal constituyen alteraciones que aparecen frecuentemente en la clínica estomatológica; por sus características y las diferentes formas de presentarse, su diagnóstico clínico con frecuencia discrepa del estudio morfológico. Por la importancia clínica de algunas de estas lesiones, nos propusimos hacer un estudio retrospectivo desde el punto de vista clínico y morfológico en 6 años (1998-2003), en los archivos de biopsias del Departamento de Pato...

  3. Trafficking of osteonectin by retinal pigment epithelial cells: evidence for basolateral secretion.

    Science.gov (United States)

    Ratnayaka, Arjuna; Paraoan, Luminita; Nelson, Glyn; Spiller, Dave G; White, Michael R H; Hiscott, Paul

    2007-01-01

    Osteonectin is a glycoprotein that modulates several aspects of cellular behaviour including proliferation and adhesion. The retinal pigment epithelium forms a continuous monolayer of polarised cells immediately bellow the neuroretina, and is integral to the homeostasis of photoreceptor cells. While osteonectin is expressed by normal retinal pigment epithelium in situ, its expression is significantly increased in retinal pigment epithelial cells associated with several common retinal diseases. This pattern of expression implies an important role for osteonectin in the biology of retinal pigment epithelial cells. However, the trafficking, processing, and eventual fate of osteonectin in these cells is not clear at present. Although the theoretical report of a leader sequence within the osteonectin open reading frame and its extracellular presence in some tissues indirectly support secretion of the protein, there is no direct experimental demonstration of the secretion route to date. As a first step towards understanding the role of osteonectin in retinal pigment epithelium, we studied the intracellular distribution and trafficking of the protein in living cells. Here, we present experimental evidence that a precursor osteonectin fusion protein is targeted to the endoplasmic reticulum/Golgi pathway, with a likely basal secretion in retinal pigment epithelial cells. In addition, we show that the precursor osteonectin protein having the leader sequence masked fails to undergo secretion leading to cell death, a phenotype which may be of relevance not only for retinal pathology, but also for other diseases such as the bone disorder known as pseudoachondroplasia that is associated with a lack of osteonectin secretion.

  4. A pigmented calcifying cystic odontogenic tumor associated with compound odontoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Borkosky Silvia S

    2007-09-01

    Full Text Available Abstract Background Pigmented intraosseous odontogenic lesions are rare with only 47 reported cases in the English literature. Among them, pigmented calcifying cystic odontogenic tumor, formerly known as calcifying odontogenic cyst, is the most common lesion with 20 reported cases. Methods A case of pigmented calcifying cystic odontogenic tumor associated with odontoma occurring at the mandibular canine-premolar region of a young Japanese boy is presented with radiographic, and histological findings. Special staining, electron microscopic study and immunohistochemical staining were also done to characterize the pigmentation. Results The pigments in the lesion were confirmed to be melanin by Masson-Fontana staining and by transmission electron microscopy. The presence of dendritic melanocytes within the lesion was also demonstrated by S-100 immunostaining. Conclusion The present case report of pigmented calcifying cystic odontogenic tumor associated with odontoma features a comprehensive study on melanin and melanocytes, including histochemical, immunohistochemical and transmission electron microscopic findings.

  5. Pigments in Thermophilic fungi

    OpenAIRE

    Somasundaram, T.; Rao, Sanjay SR; Maheshwari,R.

    1986-01-01

    UV and visible absorption spectra of thermophilic fungi were obtained by photoacoustic spectroscopy. Based on these data as well as on the chem. properties and IR spectra, it is suggested that the pigments may be hydroxylated polycyclic quinones.

  6. Photosynthetic Pigments in Diatoms

    OpenAIRE

    Paulina Kuczynska; Malgorzata Jemiola-Rzeminska; Kazimierz Strzalka

    2015-01-01

    Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvestin...

  7. Photosynthetic Pigments in Diatoms

    Directory of Open Access Journals (Sweden)

    Paulina Kuczynska

    2015-09-01

    Full Text Available Photosynthetic pigments are bioactive compounds of great importance for the food, cosmetic, and pharmaceutical industries. They are not only responsible for capturing solar energy to carry out photosynthesis, but also play a role in photoprotective processes and display antioxidant activity, all of which contribute to effective biomass and oxygen production. Diatoms are organisms of a distinct pigment composition, substantially different from that present in plants. Apart from light-harvesting pigments such as chlorophyll a, chlorophyll c, and fucoxanthin, there is a group of photoprotective carotenoids which includes β-carotene and the xanthophylls, diatoxanthin, diadinoxanthin, violaxanthin, antheraxanthin, and zeaxanthin, which are engaged in the xanthophyll cycle. Additionally, some intermediate products of biosynthetic pathways have been identified in diatoms as well as unusual pigments, e.g., marennine. Marine algae have become widely recognized as a source of unique bioactive compounds for potential industrial, pharmaceutical, and medical applications. In this review, we summarize current knowledge on diatom photosynthetic pigments complemented by some new insights regarding their physico-chemical properties, biological role, and biosynthetic pathways, as well as the regulation of pigment level in the cell, methods of purification, and significance in industries.

  8. The Development of the Ciliary Epithelium in the Embryonic Chicken Eye

    Science.gov (United States)

    1989-08-04

    experiment was to test the role of I extraocular tissues in eye growth. The periocular mesoderm ! I I was stripped away from a small area on one surface...Eichhorn and Barany , 1985). The cells in the pigmented and nonpigmented layers of the ciliary epithelium begin to differentiate from the adjacent...Statistics: The data from the individual chicken embryos in each experimental group were compared to each other and then pooled. Student’s T- test

  9. [Recurrent pigmented villonodular synovitis (PVNS)].

    Science.gov (United States)

    Neuss, M; Hermanns, B; Wirtz, D C

    2001-01-01

    The pigmented vilionodular synovitis (PVNS) is a tumour like disease of unknown origin that often shows recurrence. The pathogenesis is still unknown and therefore the question of the right therapy is not resolved. With a case report of a patient with recurrence after two arthroscopic synovectomies, PVNS is discussed against the background of the clinical, histological, and radiological features. We performed an open synovectomy and cystic lesions in both condyles of the femur and proximal tibia were filled with homologous and autologous cancellous bone. Three months later the patient had no pain and the bone density in the former cystic lesions was appropriate. The pathogenesis is still unknown. Diagnosis often is obtained much too late due to missing specific symptoms. PVNS occurs in local forms as well as in a diffuse growth pattern. Recurrence rates of up to 78% are very high. Besides arthroscopic and open synovectomy, the treatment with radiosynoviorthesis must be considered. Depending on the growth pattern, the tumour masses, and the affected joint, the therapy has to be chosen very carefully and sometimes different forms have to be combined if a recurrence--free result is to be achieved.

  10. Idiopathic eruptive macular pigmentation with papillomatosis: Report of nine cases

    Directory of Open Access Journals (Sweden)

    Joshi Rajiv

    2007-01-01

    Full Text Available Nine patients, seven males and two females aged 6-14 years, presented with extensive, asymptomatic, brown-black macules and mildly elevated, pigmented lesions of a few months′ duration. The sites affected were the face, trunk and proximal extremities. The skin lesions were discrete and individual lesions were less than 2 cm in size. The clinical diagnoses rendered by the referring physicians were lichen planus pigmentosus, urticaria pigmentosa, erythema dyschromicum perstans and postinflammatory hyperpigmentation. Histology in all nine cases showed papillomatosis of the dermis with prominent pigmentation of the basal layer (pigmented papillomatosis without any significant dermal inflammation. Two cases had spores of Pityrosporum ovale in the thickened horny layer, one of which also had, in addition, bacterial colonies in the stratum corneum. The pigmentation resolved on its own over several months. This presentation is similar to the previously described idiopathic eruptive macular pigmentation with the additional histological finding of papillomatosis that is being described for the first time and may be nosologically related to acanthosis nigricans and confluent and reticulate papillomatosis.

  11. Subretinal Pigment Epithelial Deposition of Drusen Components Including Hydroxyapatite in a Primary Cell Culture Model

    Science.gov (United States)

    Pilgrim, Matthew G.; Lengyel, Imre; Lanzirotti, Antonio; Newville, Matt; Fearn, Sarah; Emri, Eszter; Knowles, Jonathan C.; Messinger, Jeffrey D.; Read, Russell W.; Guidry, Clyde; Curcio, Christine A.

    2017-01-01

    Purpose Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Methods Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Results Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. Conclusions The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss. PMID:28146236

  12. Clinicopathological and immunohistochemical study of oral amalgam pigmentation.

    Science.gov (United States)

    Vera-Sirera, Beatriz; Risueño-Mata, Presentación; Ricart-Vayá, José M; Baquero Ruíz de la Hermosa, Carmen; Vera-Sempere, Francisco

    2012-01-01

    Amalgam tattoo, the most common exogenous oral pigmentation, can sometimes be confused with melanotic lesions, being then biopsied. We present the clinicopathological characteristics of 6 biopsied cases (5 females and 1 male) of oral amalgam pigmentation. The most common location was the gingival mucosa, followed by the buccal and palatal mucosa. Morphology and distribution (stromal, perivascular, perineural, endomysial) of pigmentation was variable; there was only 1 case with fibrous capsular reaction and likewise only a single case of granulomatous foreign body reaction. Morphological variability is conditioned by the timing and amount of the pigment deposit, which is often associated with infiltration by mast cells (CD117+), as well as overexpression of metallothionein and HLA-DR at different tissue levels.

  13. Pigmented villonodular synovitis of the spine: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Su Ok; Lee, Joo Hyuk; Yi, Jeong Geun [Cheongju St. Mary' s Hospital, Cheongju (Korea, Republic of)

    2000-10-01

    Pigmented villonodular synovitis (PVNS) is a synovial lesion of joints or tendon sheaths, characterized by villous and nodular overgrowth of the synovial membrane. It commonly occurs in synovial joints of the appendicular skeleton, particularly those of the knee and hip, but rarely affecting those of the spine. We report a case of PVNS of the lumbar spine mimicking epidural mass.

  14. True bursal pigmented villonodular synovitis

    Energy Technology Data Exchange (ETDEWEB)

    Abdelwahab, Ibrahim Fikry [Department of Radiology, New York Methodist Hospital, Affiliated with New York Hospital-Cornell Medical Center, Brooklyn, NY (United States); Kenan, Samuel [Department of Orthopedics, New York University Medical Center, NY (United States); Steiner, German C. [Department of Pathology, Hospital for Joint Diseases/Orthopedic Institute, New York, NY (United States); Abdul-Quader, Mohammed [Department of Radiology, New York Presbyterian Hospital, Columbia University, New York, NY (United States)

    2002-06-01

    We describe two cases of pigmented villonodular synovitis affecting true bursae. This study was also designed to discuss the term ''pigmented villonodular bursitis'', not confined to true synovial bursae, sometimes creating misunderstanding. (orig.)

  15. Oral epithelium in diabetics: A cytomorphometric correlation

    Directory of Open Access Journals (Sweden)

    K P Nandita

    2014-01-01

    Full Text Available Objectives: The study aims to establish an etiological association between diabetes and precancerous lesions of the oral cavity by cytomorphometric analysis of the oral epithelium. Study Design: Smears were obtained from three distinct oral sites - buccal mucosa, dorsum of the tongue and the floor of the mouth in ten controls and ten patients previously diagnosed with type II diabetes. The oral smears were stained with Papanicolaou SA-36 solution. An eye - piece graticule was used to obtain the cytoplasm and nuclear dimension; where larger dimension was denoted as "D" and the smaller dimension was denoted as "d". The nuclear area (NA, nuclear diameter (ND, cytoplasmic area (CA and the cytoplasmic / nuclear ratio (C/N were evaluated from 50 cells predominant in each oral site. Statistical Analysis: The cytomorphometric data obtained was compared between the group of diabetic patients and the control groups using the student′s t- test (SPSS version 11.0. Results: Results showed that the nuclear area and the nuclear diameter of oral epithelial cells were increased in diabetic patients, as compared to non- diabetics, while the non- diabetic patients demonstrated an increase in nuclear ratio. Conclusions: The results from this study suggest that diabetes mellitus can cause alterations in oral epithelial cells that are detectable with exfoliative cytology.

  16. So-called embryonal hyperplasia of Bowman's capsular epithelium: an immunohistochemical and ultrastructural study.

    Science.gov (United States)

    Ogata, K; Hajikano, H; Sakaguchi, H

    1991-01-01

    The so-called embryonal hyperplasia of Bowman's capsular epithelium (EHBCE) is a rather specific lesion occurring in kidneys of patients maintained on chronic dialysis. It consists of poorly differentiated cells proliferating around sclerosed or obsolescent glomeruli. In this study, immunohistochemical and ultrastructural characterization of EHBCE was performed. The poorly differentiated cells in the lesion exhibited a positive reaction for vimentin and a negative one for cytokeratin (PKK 1) and epithelial membrane antigen. On ultrastructural examination, specialized junctions between adjoining cells, microvilli-like structures on their surfaces, and immature basal folds were observed. These observations suggest that the cells of EHBCE may be associated with the anlage of glomerular epithelium. The background in which neoplasms like renal cell carcinoma or atypical epithelium of cyst wall develop in end-stage kidneys of adult patients on long-term dialysis may cause such a proliferation of poorly differentiated cells in young or paediatric age group patients.

  17. Raman af hvide pigmenter

    DEFF Research Database (Denmark)

    Reeler, Nini Elisabeth Abildgaard; Nielsen, Ole Faurskov; Sauer, Stephan P. A.;

    2013-01-01

    Et samspil mellem kunst og kemi. I et samarbejde mellem Statens Museum for Kunst og Kemisk Institut på KU er Ramanspek-troskopi brugt til at definere sammensætningen af blandinger af blyhvidt og calcit i maleriers hvide pigmenter....

  18. Pigmented villonodular synovitis

    Energy Technology Data Exchange (ETDEWEB)

    Al-Nakshabandi, N.A.; Ryan, A.G.; Choudur, H.; Torreggiani, W.; Nicoloau, S.; Munk, P.L. E-mail: plmunk@interchange.ubc.ca; Al-Ismail, K

    2004-05-01

    Pigmented villonodular synovitis (PVNS) is a rare benign proliferative growth of the synovium of obscure aetiology with a wide spectrum of clinical presentations and imaging findings. The purpose of this review is to acquaint the reader with the spectrum of imaging features of PVNS using a variety of imaging techniques.

  19. Using of cyanobacteria pigments

    OpenAIRE

    Кардаш, О. В.; Національний авіаційний університет; Курейшевич, А. В.; Інститут гідробіології НАН України; Васильченко, О. А.; Національний авіаційний університет

    2012-01-01

    Photosynthetic apparatus of all organisms contains light absorbing pigments. Cyanobacteria pigments may be divided into three groups – chlorophylls, carotenoids and phycobiliproteins. Pigments may be used in the food and pharmaceutical industry. Cyanobacteria pigments features and usage possibilities are observed. Фотосинтезирующий аппарат всех организмов состоит из поглощающих свет пигментов. Пигменты цианобактерий можно разделить на три группы – хлорофиллы, каротиноиды и фикобилипротеины...

  20. Raman af hvide pigmenter

    DEFF Research Database (Denmark)

    Reeler, Nini Elisabeth Abildgaard; Nielsen, Ole Faurskov; Sauer, Stephan P. A.

    2013-01-01

    Et samspil mellem kunst og kemi. I et samarbejde mellem Statens Museum for Kunst og Kemisk Institut på KU er Ramanspek-troskopi brugt til at definere sammensætningen af blandinger af blyhvidt og calcit i maleriers hvide pigmenter....

  1. Phototrophic pigment production with microalgae

    NARCIS (Netherlands)

    Mulders, K.J.M.

    2014-01-01

    Abstract

    Microalgal pigments are regarded as natural alternatives for food colorants. To facilitate optimization of microalgae-based pigment production, this thesis aimed to obtain key insights in the pigment metabolism of phototrophic microalgae, with the main  focus

  2. Phototrophic pigment production with microalgae

    NARCIS (Netherlands)

    Mulders, K.J.M.

    2014-01-01

    Abstract

    Microalgal pigments are regarded as natural alternatives for food colorants. To facilitate optimization of microalgae-based pigment production, this thesis aimed to obtain key insights in the pigment metabolism of phototrophic microalgae, with the main  focus

  3. Effects of hypoxia on the expression of human retinal pigment epithelium cells cultured in vitro%缺氧对体外培养的人视网膜色素上皮细胞热休克蛋白47表达的影响

    Institute of Scientific and Technical Information of China (English)

    曾爱萍; 曾水清; 吕明良; 程扬

    2006-01-01

    目的:探讨缺氧对体外培养的人视网膜色素上皮(retinal pigment epitelium,RPE)细胞热休克蛋白47(heat shock protein 47,HSP47)表达的影响.方法:培养的人RPE细胞分为两组:缺氧组使用化学缺氧诱导剂CoCl2模拟RPE细胞缺氧环境来培养人RPE细胞,对照组置入正常环境中培养.采用半定量RT-PCR检测人RPE细胞中HSP47mRNA的表达,Western blot蛋白印迹分析检测人RPE细胞中蛋白水平.结果:缺氧组AHSP47/Aβ-actin比值为1.46±0.15与对照组比值0.94±0.13比较,差异有显著意义(P<0.05).同时缺氧组HSP47蛋白含量平均A值为728.03±38.15显著高于正常对照组平均A值571.47±26.95,差异有统计学意义(P<0.05).结论:HSP47在缺氧状态下异常高表达.

  4. LOCALIZED PIGMENTED VILLONODULAR SYNOVITIS: CASE REPORT

    Science.gov (United States)

    Carvalho Godoy, Fabiola Andrea de; Faustino, Carlos Alberto Cury; Meneses, Cláudio Santos; Nishi, Sergio Tadao; Góes, César Eduardo Giancoli; Canto, Abaeté Leite do

    2015-01-01

    This case concerned a female patient with a complaint of pain in the anterior region of her left knee during and after sports activities, followed by joint blockage three months ago. From imaging examinations, simple radiography of the knee was normal and magnetic resonance showed a solid expansive mass, possibly corresponding to soft-tissue chondroma or focal nodular synovitis. Arthroscopic resection of the lesion was performed, and the diagnosis of diffuse giant cell tumor resembling localized pigmented villonodular synovitis (PVNS) was made from the result of the anatomopathological examination. The patient presented good clinical evolution, with disappearance of symptoms and return to physical activities. PMID:27027040

  5. LOCALIZED PIGMENTED VILLONODULAR SYNOVITIS: CASE REPORT.

    Science.gov (United States)

    Carvalho Godoy, Fabiola Andrea de; Faustino, Carlos Alberto Cury; Meneses, Cláudio Santos; Nishi, Sergio Tadao; Góes, César Eduardo Giancoli; Canto, Abaeté Leite do

    2011-01-01

    This case concerned a female patient with a complaint of pain in the anterior region of her left knee during and after sports activities, followed by joint blockage three months ago. From imaging examinations, simple radiography of the knee was normal and magnetic resonance showed a solid expansive mass, possibly corresponding to soft-tissue chondroma or focal nodular synovitis. Arthroscopic resection of the lesion was performed, and the diagnosis of diffuse giant cell tumor resembling localized pigmented villonodular synovitis (PVNS) was made from the result of the anatomopathological examination. The patient presented good clinical evolution, with disappearance of symptoms and return to physical activities.

  6. Connexins form functional hemichannels in porcine ciliary epithelium.

    Science.gov (United States)

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor.

  7. Tight Junctions in Salivary Epithelium

    Directory of Open Access Journals (Sweden)

    Olga J. Baker

    2010-01-01

    Full Text Available Epithelial cell tight junctions (TJs consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium.

  8. Determination of pigments in vegetables.

    Science.gov (United States)

    Schoefs, Benoît

    2004-10-29

    Plant pigments are responsible for the shining color of plant tissues. They are also found in animal tissues and, eventually in transformed food products as additives. These pigments have an important impact on the commercial value of products, because the colors establish the first contact with the consumer. In addition plant pigments may have an influence on the health of the consumers. Pigments are labile: they can be easily altered, and even destroyed. Analytical processes have been developed to determine pigment composition. The aim of this paper is to provide a brief overview of these methods.

  9. Pigmented ameloblastic fibro-odontoma: clinical, histological, and immunohistochemical profile.

    Science.gov (United States)

    Martínez Martínez, Marisol; Romero, Celeste Sánchez; Piña, Alicia Rumayor; Palma Guzmán, José Mario; de Almeida, Oslei Paes

    2015-02-01

    Ameloblastic fibro-odontoma (AFO) is a slow-growing, expansive, benign odontogenic tumor, composed of ameloblastic epithelium embedded in an ectomesenchymal stroma resembling dental papilla, containing hard dental tissue in variable degrees of maturation, including enamel, dentin, and sometimes cementum. AFO typically affects the posterior mandible, causing bony expansion. We report a case of pigmented AFO in a 5-year-old boy, comprising clinical and histological features illustrated by immunohistochemistry using a large panel of antibodies, polarized light microscopy and scanning electron microscopy.

  10. Pigmentos maculares Macular pigments

    Directory of Open Access Journals (Sweden)

    Renata Canovas

    2009-12-01

    Full Text Available A luteína e a zeaxantina são pigmentos amarelos que se localizam na mácula. Devido à sua localização, diminuem e filtram a quantidade de luz principalmente azul que chega aos fotorreceptores, atuam como antioxidantes e podem melhorar a qualidade visual. Esta é uma revisão do seu mecanismo de incorporação, ação, possíveis aplicações e conhecimento científico a respeito.Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update.

  11. Pigment dispersion syndrome

    Directory of Open Access Journals (Sweden)

    C.S. Sandhya

    2013-10-01

    Full Text Available We report of the rare occurrence of pigment dispersion syndrome (PDS with posterior subcapsular cataract in both eyes in a young male patient. The patient presented with complaints of progressive decrease in vision of one year duration. The patient also had high myopia with mild iridodonesis, phacodonesis and anterior insertion of zonules. Classical signs of PDS like Krukenberg's spindle on the posterior corneal surface were evident on slit lamp examination; transillumination defects in the iris could not be elicited by retroillumination as the iris was heavily pigmented. Gonioscopy revealed heavy and uniform pigmentation of trabecular meshwork. Evidence of a characteristic iris configuration on optical coherence tomography (OCT, namely, posterior bowing of iris in the mid periphery suggested the diagnosis of PDS. This case highlights the importance of OCT in identifying the iris configuration characteristically seen in PDS even in the absence of transillumination defects in the iris and reiterates the need to look for subtle signs like phacodonesis which are important when surgical intervention is planned.

  12. Pigmented basal cell carcinoma of the eyelid in Hispanics

    Directory of Open Access Journals (Sweden)

    Lily Koo Lin

    2008-10-01

    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  13. Idiopathic eruptive macular pigmentation: report of 10 cases.

    Science.gov (United States)

    Jang, K A; Choi, J H; Sung, K S; Moon, K C; Koh, J K

    2001-02-01

    Idiopathic eruptive macular pigmentation (IEMP) is a rare disease. IEMP is characterized by asymptomatic, pigmented macules involving the neck, trunk, and proximal extremities. This study describes 10 cases of idiopathic eruptive macular pigmentation seen during a 9-year period at the Asan Medical Center, Seoul, Korea. We present these characteristic consecutive cases to provide more insight into the clinical picture and course of IEMP. Skin lesions of 8 patients were multiple brown macules involving the trunk, face, neck, and extremities. In 2 patients, multiple dark brown macules and patches were noted. The age of onset varied from 1 to 20 years. Tentative diagnoses were usually ashy dermatosis (erythema dyschromicum perstans), fixed drug eruption, or mastocytosis. The history of any erythema and drug medication was absent. Darier's sign was absent. Skin biopsy specimens showed increased pigmentation of the basal layer in an otherwise normal epidermis. Pigmentary incontinence, melanophages, and mild perivascular lymphohistiocytic infiltrate in the papillary dermis were also revealed. Mast cells could not be found. The lesions gradually disappeared during a period of several months to years. The alleged rarity of IEMP may be partially caused by medical unfamiliarity with this entity, despite its clinical and histopathologic characteristic picture. Treatment of IEMP is unnecessary because spontaneous resolution of the lesions can be expected within several months to a few years.

  14. Amalgam contact hypersensitivity lesion: an unusual presentation-report of a rare case.

    Science.gov (United States)

    Ramnarayan, Bk; Maligi, Pm; Smitha, T; Patil, Us

    2014-09-01

    Amalgam or its components may cause Type IV hypersensitivity reactions on the oral mucosa. These amalgam contact hypersensitivity lesions (ACHL) present as white striae and plaques, erythematous, erosive, atrophic, or ulcerative lesions. Postinflammatory pigmentation in such lesions and pigmentation due to amalgam incorporation in the soft tissue have been reported in the literature. However, ACHL presenting primarily as a black pigmented lesion is extremely rare if not reported. The clinician should be aware of one such presentation of ACHL; we report a unique case of ACHL in a 30-year-old female with such a pigmented lesion in close contact with amalgam restorations. The lesion regressed considerably in a year after replacement of the restoration with posterior composites.

  15. Voltage-gated potassium channel Kvl.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium

    Institute of Scientific and Technical Information of China (English)

    LI Yan-feng; ZHUO Ye-hong; BI Wei-na; BAI Yu-jing; LI Yan-na; WANG Zhi-jian

    2008-01-01

    Background The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance.Ion channels play an important role in these processes.The main aim of this study was to determine whether the well-characterized members of the Kvl family (Kv1.3) contribute to the Kv currents in ciliary epithelium.Methods New Zealand White rabbits were maintained in a 12 hours light/dark cycle.Ciliary epithelium samples were isolated from the rabbits.We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kvl.3 in ciliary body epithelium.Membrane potential change after adding of Kv1.3 inhibitor margatoxin (MgTX) was observed with a fluorescence method.Results Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium,however it seemed to express more in the apical membrane of the nonpigmented epithelial cells.One nmol/L margatoxin,a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium (NPE) membrane potential.The cytosotic calcium increased after NPE cell depolarization,this increase of cytosolic calcium was partially blocked by 12.5 μmol/L dantrolene and 10 μmol/L nifedipine.These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms.Conclusion Kv1.3 channels contribute to K+ efflux at the membrane of rabbit ciliary epithelium.

  16. Premalignant Lesions in the Kidney

    Directory of Open Access Journals (Sweden)

    Ziva Kirkali

    2001-01-01

    Full Text Available Renal cell carcinoma (RCC is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1 morphological similarity; (2 spatial association; (3 development of microinvasive carcinoma; (4 higher frequency, severity, and extent then invasive carcinoma; (5 progression to invasive cancer; and (6 similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  17. Generation of retinal pigment epithelial cells from human embryonic stem cell-derived spherical neural masses.

    Science.gov (United States)

    Cho, Myung Soo; Kim, Sang Jin; Ku, Seung-Yup; Park, Jung Hyun; Lee, Haksup; Yoo, Dae Hoon; Park, Un Chul; Song, Seul Ae; Choi, Young Min; Yu, Hyeong Gon

    2012-09-01

    Dysfunction and loss of retinal pigment epithelium (RPE) are major pathologic changes observed in various retinal degenerative diseases such as aged-related macular degeneration. RPE generated from human pluripotent stem cells can be a good candidate for RPE replacement therapy. Here, we show the differentiation of human embryonic stem cells (hESCs) toward RPE with the generation of spherical neural masses (SNMs), which are pure masses of hESCs-derived neural precursors. During the early passaging of SNMs, cystic structures arising from opened neural tube-like structures showed pigmented epithelial morphology. These pigmented cells were differentiated into functional RPE by neuroectodermal induction and mechanical purification. Most of the differentiated cells showed typical RPE morphologies, such as a polygonal-shaped epithelial monolayer, and transmission electron microscopy revealed apical microvilli, pigment granules, and tight junctions. These cells also expressed molecular markers of RPE, including Mitf, ZO-1, RPE65, CRALBP, and bestrophin. The generated RPE also showed phagocytosis of isolated bovine photoreceptor outer segment and secreting pigment epithelium-derived factor and vascular endothelial growth factor. Functional RPE could be generated from SNM in our method. Because SNMs have several advantages, including the capability of expansion for long periods without loss of differentiation capability, easy storage and thawing, and no need for feeder cells, our method for RPE differentiation may be used as an efficient strategy for generating functional RPE cells for retinal regeneration therapy.

  18. Autofluorescence guided diagnostic evaluation of suspicious oral mucosal lesions: opportunities, limitations, and pitfalls

    Science.gov (United States)

    Vigneswaran, Nadarajah

    2011-03-01

    Wide-filed autofluorescence examination is currently considered as a standard of care for screening and diagnostic evaluation of early neoplastic changes of the skin, cervix, lung, bladder, gastrointestinal tract and oral cavity. Naturally occurring fluorophores within the tissue absorb UV and visible light and can re-emit some of this light at longer wavelengths in the form of fluorescence. This non-invasive tissue autofluorescence imaging is used in optical diagnostics, especially in the early detection of cancer. Usually, malignant transformation is associated with thickening of the epithelium, enhanced cellular density due to increased nuclear cytoplasmic ratio which may attenuate the excitation leading to a decrease in collagen autofluorescence. Hence, dysplastic and cancerous tissues often exhibit decreased blue-green autofluorescence and appear darker compared to uninvolved mucosa. Currently, there are three commercially available devices to examine tissue autofluorescence in the oral cavity. In this study we used the oral cancer screening device IdentafiTM 3000 to examine the tissue reflectance and autofluorescence of PML and confounding lesions of the oral cavity. Wide-field autofluorescence imaging enables rapid inspection of large mucosal surfaces, to aid in recognition of suspicious lesions and may also help in discriminate the PML (class 1) from some of the confounding lesions (class II). However, the presence of inflammation or pigments is also associated with loss of stromal autofluorescence, and may give rise to false-positive results with widefield fluorescence imaging. Clinicians who use these autofluorescence based oral cancer screening devices should be aware about the benign oral mucosal lesions that may give false positivity so that unnecessary patient's anxiety and the need for scalpel biopsy can be eliminated.

  19. Nonphotosynthetic Pigments as Potential Biosignatures

    CERN Document Server

    Schwieterman, Edward W; Meadows, Victoria S

    2015-01-01

    Previous work on possible surface reflectance biosignatures for Earth-like planets has typically focused on analogues to spectral features produced by photosynthetic organisms on Earth, such as the vegetation red edge. Although oxygenic photosynthesis, facilitated by pigments evolved to capture photons, is the dominant metabolism on our planet, pigmentation has evolved for multiple purposes to adapt organisms to their environment. We present an interdisciplinary study of the diversity and detectability of nonphotosynthetic pigments as biosignatures, which includes a description of environments that host nonphotosynthetic biologically pigmented surfaces, and a lab-based experimental analysis of the spectral and broadband color diversity of pigmented organisms on Earth. We test the utility of broadband color to distinguish between Earth-like planets with significant coverage of nonphotosynthetic pigments and those with photosynthetic or nonbiological surfaces, using both 1-D and 3-D spectral models. We demonstr...

  20. Choroidal neovascularization secondary to choroidal nevus simulating an inflammatory lesion

    Directory of Open Access Journals (Sweden)

    Samuray Tuncer

    2013-01-01

    Full Text Available Choroidal nevi are the most common benign pigmented lesions of the fundus. Choroidal neovascularization is a rare complication of choroidal nevi. We report herein a young patient managed successfully with intravitreal bevacizumab injections for juxtapapillary choroidal neovascularization secondary to choroidal nevus simulating an inflammatory lesion.

  1. Lesiones laborales

    OpenAIRE

    2015-01-01

    Las lesiones laborales se producen por un esfuerzo repetitivo, cuando un exceso de presión se ejerce sobre una parte del cuerpo provocando lesiones óseas, articulares, musculares y daños en los tejidos. Los accidentes laborales también pueden producir una lesión en el organismo y esto sumado a diversos factores es un problema para la reinserción laboral de los trabajadores de la energía eléctrica. Objetivo: Establecer cuáles son las lesiones más frecuentes que afectan a los ...

  2. Granulomatous reaction to red tattoo pigment treated with allopurinol.

    Science.gov (United States)

    Godinho, Mariana Marteleto; Aguinaga, Felipe; Grynszpan, Rachel; Lima, Victor Maselli; Azulay, David Rubem; Cuzzi, Tullia; Ramos-E-Silva, Marcia; Manela-Azulay, Mônica

    2015-09-01

    Granulomatous reactions to tattoo ink are most commonly associated with mercury sulfide, a component of red pigments. Treatment options show limited results. Allopurinol, an inhibitor of xanthine oxidase, has been reported as a successful alternative treatment to granulomatous disorders, such as sarcoidosis and granulomatous reactions to fillers and tattoos. We report a case of granulomatous reaction to red tattoo pigment treated with allopurinol for 6 months. Good clinical improvement could be noticed during this time. Two months after we stopped the treatment, the lesion recurred. Allopurinol emerges as an important drug for the management of granulomatous reactions caused by tattoo pigments. Based on the significant clinical improvement noticed during its use, we recommend new studies to elucidate all the potential benefits of the use of allopurinol for the treatment of granulomatous reactions to tattoo ink.

  3. Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2017-01-01

    Full Text Available Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated and rough (squamous epithelium-originated. Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic, and mesenchymal lesions (benign and malignant neoplasms. In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

  4. Peripheral ameloblastoma in-situ: an evidential fact of surface epithelium origin.

    Science.gov (United States)

    Ide, Fumio; Mishima, Kenji; Miyazaki, Yuji; Saito, Ichiro; Kusama, Kaoru

    2009-11-01

    The proposed origin from the adult gingival epithelium for peripheral ameloblastoma is difficult to prove and still remains unresolved. This report details a small fibrous polyp on the maxillary edentulous ridge of a 73-year-old woman, in which the basal layer of covering squamous epithelium dipped down toward the lamina propria over a wide area. Basal cells of the downgrowth were ameloblastic in type, and bulbous parts assumed an appearance of the bud-shaped enamel organ. Multiple sectioning failed to detect any epithelial nests in the submucosa. In addition to the morphologic overlap, early ameloblastoma epithelia shared antigenic properties with tumor cells of representative control examples of peripheral ameloblastoma. This is the first description of an in situ lesion of peripheral ameloblastoma, to our knowledge, and its multifocal ameloblastoma changes can be accepted as a direct proof of origin from the surface epithelium.

  5. Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids.

    OpenAIRE

    2002-01-01

    PURPOSE: To show that fish oil-derived omega-3 polyunsaturated fatty acids, delivered to the retinal pigment epithelium (RPE) by circulating low-density lipoproteins (LDL), enhance already considerable RPE lysosomal acid lipase activity, providing for more efficient hydrolysis of intralysosomal RPE lipids, an effect that may help prevent development of age-related macular degeneration (ARMD). METHODS: Colorimetric biochemical and histochemical techniques were used to demonstrate RPE acid lipa...

  6. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    Science.gov (United States)

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

  7. Permeability and ultrastructure of human bladder epithelium

    DEFF Research Database (Denmark)

    Eldrup, J; Thorup, Jørgen Mogens; Nielsen, S L;

    1983-01-01

    Leakage of tight junctions as observed with electron microscopy and demonstration of solute transport across bladder epithelium was investigated in 13 patients with different bladder diseases: urinary retention and infection, bladder tumours and interstitial cystitis. The latter group showed cons...

  8. Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

    Science.gov (United States)

    Olszewska, E; Sudhoff, H

    2007-01-01

    Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

  9. Airway Epithelium Stimulates Smooth Muscle Proliferation

    OpenAIRE

    Malavia, Nikita K.; Raub, Christopher B.; Mahon, Sari B.; Brenner, Matthew; Reynold A Panettieri; George, Steven C.

    2009-01-01

    Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air–liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (...

  10. Effects of Cordyceps sinensis cultivated by artificial fermentation on expression of pigment epithelium-derived factor and matrix metalloproteinase-2 in diabetic rat kidney%人工发酵虫草菌丝体干粉对糖尿病大鼠肾脏组织色素上皮衍生因子和基质金属蛋白酶-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    宋庆芳; 谈力欣; 王战建

    2011-01-01

    目的 观察人工发酵虫草菌丝体干粉对糖尿病大鼠肾组织中色素上皮衍生因子(PEDF)、基质金属蛋白酶-2(MMP-2)和转化生长因子-β1(TGF-β1)表达的影响.方法 依照随机区组设计将45只体质量为180~220 g的8周龄雄性SD大鼠随机分为3组:正常对照组(A组,n=15)、糖尿病对照组(B组,n=15)、人工发酵虫草菌丝体干粉干预组(C组,n=15).B组和C组大鼠腹腔注射55 μg/g链脲佐菌素制作糖尿病动物模型.造模成功后第3天,C组给予4 μg·g-1·d-1人工发酵虫草菌丝体干粉定时灌胃,A组、B组以等体积生理盐水灌胃.实验12周末,观察比较3组肾脏指数(KI)、血肌酐(Scr)、尿素氮(BUN)、24 h尿量、24 h尿白蛋白排泄量(UAE)、总胆固醇(TC)、甘油三酯(TG).免疫组化方法分析比较3组PEDF、MMP-2和TGF-β1在肾组织中的表达,实时定量-聚合酶链反应(RT-PCR)分析比较3组PEDF mRNA的表达情况.两组间比较采用t检验,多组间比较采用方差分析.结果 B、C组大鼠KI、BUN、SCr、UAE、TC、TG均高于A组(均P<0.01),C组均较B组降低(均P<0.01).免疫组化显示,B组和C组肾脏PEDF(1.53±0.12、2.60±0.15)、MMP-2(1.8±0.5、3.3±0.4)表达均低于A组(3.96±0.14、4.3±0.6)(均P<0.01),TGF-β1(4.60±0.15、2.60±0.09)表达均高于A组(1.57±0.09)(均P<0.01),而C组PEDF、MMP-2表达高于B组(P<0.01),TGF-β1表达低于B组(P<0.01).RT-PCR分析显示B、C组肾脏组织中PEDF mRNA表达量为0.3±0.1和0.8±0.2,显著低于A组(1.2±0.3)(均P<0.01),而C组高于B组(P<0.01).结论 肾脏组织中PEDF、MMP-2和TGF-β1表达的改变可能参与了糖尿病肾病的发生.人工发酵虫草菌丝体干粉可改善肾功能、调节血脂,还可通过调节PEDF、MMP-2及TGF-β1在肾脏的表达发挥肾脏保护作用.%Objective To investigate the effects of Cordyceps sinensis cultivated by artificial fermentation on the expression of pigment epithelium-derived factor(PEDF), matrix metalloproteinase

  11. Gene expression based evidence of innate immune response activation in the epithelium with oral lichen planus.

    Science.gov (United States)

    Adami, Guy R; Yeung, Alexander C F; Stucki, Grant; Kolokythas, Antonia; Sroussi, Herve Y; Cabay, Robert J; Kuzin, Igor; Schwartz, Joel L

    2014-03-01

    Oral lichen planus (OLP) is a disease of the oral mucosa of unknown cause producing lesions with an intense band-like inflammatory infiltrate of T cells to the subepithelium and keratinocyte cell death. We performed gene expression analysis of the oral epithelium of lesions in subjects with OLP and its sister disease, oral lichenoid reaction (OLR), in order to better understand the role of the keratinocytes in these diseases. Fourteen patients with OLP or OLR were included in the study, along with a control group of 23 subjects with a variety of oral diseases and a normal group of 17 subjects with no clinically visible mucosal abnormalities. Various proteins have been associated with OLP, based on detection of secreted proteins or changes in RNA levels in tissue samples consisting of epithelium, stroma, and immune cells. The mRNA level of twelve of these genes expressed in the epithelium was tested in the three groups. Four genes showed increased expression in the epithelium of OLP patients: CD14, CXCL1, IL8, and TLR1, and at least two of these proteins, TLR1 and CXCL1, were expressed at substantial levels in oral keratinocytes. Because of the large accumulation of T cells in lesions of OLP it has long been thought to be an adaptive immunity malfunction. We provide evidence that there is increased expression of innate immune genes in the epithelium with this illness, suggesting a role for this process in the disease and a possible target for treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Paraneoplastic disorders of hair, nails, oral mucosa and pigmentation

    Directory of Open Access Journals (Sweden)

    Ayşe Kavak

    2013-12-01

    Full Text Available In this section, paraneoplastic entites of hair, nail, oral mucosa and pigmentation changes have been discussed. Some skin findings are “strong” indicator of a malignancy whereas others are not. Readers will encounter some “coincidental” or “common” entities as well as more “severe” changes for a paraneoplastic sign. In addition, it is crucial that some paraneoplastic lesions may predict for a recurrence of malignancy.

  13. Natural pigments and sacred art

    Science.gov (United States)

    Kelekian, Lena, ,, Lady

    2010-05-01

    Since the dawn of mankind, cavemen has expressed himself through art. The earliest known cave paintings date to some 32,000 years ago and used 4 colours derived from the earth. These pigments were iron oxides and known as ochres, blacks and whites. All pigments known by the Egyptians, the Greeks, the Romans and Renaissance man were natural and it was not until the 18th century that synthetic pigments were made and widely used. Until that time all art, be it sacred or secular used only natural pigments, of which the preparation of many have been lost or rarely used because of their tedious preparation. As a geologist, a mineralogist and an artist specializing in iconography, I have been able to rediscover 89 natural pigments extracted from minerals. I use these pigments to paint my icons in the traditional Byzantine manner and also to restore old icons, bringing back their glamour and conserving them for years to come. The use of the natural pigments in its proper way also helps to preserve the traditional skills of the iconographer. In the ancient past, pigments were extremely precious. Many took an exceedingly long journey to reach the artists, and came from remote countries. Research into these pigments is the work of history, geography and anthropology. It is an interesting journey in itself to discover that the blue aquamarines came from Afghanistan, the reds from Spain, the greens Africa, and so on. In this contribution I will be describing the origins, preparation and use of some natural pigments, together with their history and provenance. Additionally, I will show how the natural pigments are used in the creation of an icon. Being a geologist iconographer, for me, is a sacrement that transforms that which is earthly, material and natural into a thing of beauty that is sacred. As bread and wine in the Eucharist, water during baptism and oil in Holy Union transmit sanctification to the beholder, natural pigments do the same when one considers an icon. The

  14. Optimizing modulation frequency for structured illumination in a fiber-optic microendoscope to image nuclear morphometry in columnar epithelium.

    Science.gov (United States)

    Keahey, P A; Tkaczyk, T S; Schmeler, K M; Richards-Kortum, R R

    2015-03-01

    Fiber-optic microendoscopes have shown promise to image the changes in nuclear morphometry that accompany the development of precancerous lesions in tissue with squamous epithelium such as in the oral mucosa and cervix. However, fiber-optic microendoscopy image contrast is limited by out-of-focus light generated by scattering within tissue. The scattering coefficient of tissues with columnar epithelium can be greater than that of squamous epithelium resulting in decreased image quality. To address this challenge, we present a small and portable microendoscope system capable of performing optical sectioning using structured illumination (SI) in real-time. Several optical phantoms were developed and used to quantify the sectioning capabilities of the system. Columnar epithelium from cervical tissue specimens was then imaged ex vivo, and we demonstrate that the addition of SI achieves higher image contrast, enabling visualization of nuclear morphology.

  15. Odontogenic Cyst with Verrucous Proliferation Exhibiting Melanin Pigmentation

    Science.gov (United States)

    Soni, Krupa Mehta; Ahmed, Junaid; Bhat, Keshava; Kottieth Pallam, Nandita; Lewis, Amitha Juanita

    2017-01-01

    Verrucous proliferation arising from odontogenic cysts is a rare entity. We report an unusual case of an infected odontogenic cyst with verrucous proliferation and melanin pigmentation in a 13-year-old male patient who presented with an intraoral swelling in relation to impacted teeth 26 and 27. The enucleated lesion was diagnosed as an odontogenic keratocyst and the patient died within two years of presentation due to multiple recurrences. The clinical, radiological, and microscopic features of the lesion are presented with an attempt to discuss the etiopathogenesis. The case hereby reported is uncommon with only eight cases reported in the literature. PMID:28409045

  16. Refractory Pigmentation Associated with Laugier-Hunziker Syndrome following Er:YAG Laser Treatment.

    Science.gov (United States)

    Ergun, Sertan; Saruhanoğlu, Alp; Migliari, Dante-Antonio; Maden, Ilay; Tanyeri, Hakkı

    2013-01-01

    The present report describes a case of Laugier-Hunziker syndrome (LHS), a rare benign condition. A patient with LHS develops acquired melanotic pigmentation of the lips and buccal mucosa, often with pigmentation of the nails occurring. No systemic symptoms are associated with this syndrome. Normally, no treatment is required for this condition, unless for aesthetic reason, mainly due to pigmentation on the lip mucosa. We present a case of LHS, 37-year-old female, whose pigmentations on her lip and in the oral cavity were treated with an Er:YAG laser. At the postoperative 12th month followup, the lesions recurred. The effects of any surgical attempt to treat pigmentations associated with LHS were discussed.

  17. Pigmented villonodular synovitis of the thoracic spine: case report and review of the literature

    OpenAIRE

    Arnold, Paul M.; Dunlay,Ryan P.; Haynes,Neal G.; Ossama Tawfik; Jacob Hodges

    2009-01-01

    Pigmented Villonodular Synovitis (PVNS), a lesion of the synovial tissues, is rarely found in the spine. We present a 73-year-old male with increasing lower extremity weakness and paresthesias. MRI scans revealed disc herniation and spinal cord compression at the T11-T12 and T12- L1 levels. Intraoperative exploration revealed an epidural mass originating in the T12 lamina, compressing the spinal cord at T11-T12. Pathologic examination was consistent with pigmented villonodular synovitis.Sinov...

  18. Cadmium induced histopathology in the olfactory epithelium of a snakehead fish, Channa punctatus (Bloch

    Directory of Open Access Journals (Sweden)

    Debraj Roy

    2013-10-01

    Full Text Available Histopathology on the olfactory organ of a snakehead fish, Channa punctatus (Bloch, 1793 were assessed after exposing the fish to 2.5 mg/L and 5mg/L of CdCl2 for 15 days, 30 days and 45 days. Cellular organization of the epithelium was affected severely with degeneration of sensory and supporting cells and hyperplasia of basal cells and mucous cells. Mucous cell proliferation indicates the upregulation of mucous secretion to protect the epithelium from toxic effect of cadmium. The olfactory epithelium was endowed with the multipotent basal cells which differentiate into sensory cells, supporting cells and other cell types of the epithelium during normal cells turn over and in the event of cell death.  However, due to cadmium exposure proliferating basal cells failed to differentiate into normal cells and the undifferentiated proliferated cell formed lump and intraepithelial lesion altering the composition of the entire epithelium. Present study indicates that in prolonged exposure to cadmium chloride olfactory functions of the fish might be impaired due to loss of all sensory cells.

  19. Pigmented villonodular synovitis: radiologic-pathologic correlation.

    Science.gov (United States)

    Murphey, Mark D; Rhee, John H; Lewis, Rachel B; Fanburg-Smith, Julie C; Flemming, Donald J; Walker, Eric A

    2008-01-01

    Pigmented villonodular synovitis (PVNS) represents an uncommon benign neoplastic process that may involve the synovium of the joint diffusely or focally (PVNS) or that may occur extraarticularly in a bursa (pigmented villonodular bursitis [PVNB]) or tendon sheath (pigmented villonodular tenosynovitis [PVNTS]). Pathologic specimens of the hypertrophic synovium may appear villous, nodular, or villonodular, and hemosiderin deposition, often prominent, is seen in most cases. The knee, followed by the hip, is the most common location for PVNS or PVNB, whereas PVNTS occurs most often in the hand and foot. PVNTS is also referred to as giant cell tumor of the tendon sheath (GCTTS). PVNTS is the most common form of this disease by a ratio of approximately 3:1. Radiographs reveal nonspecific features of a joint effusion in PVNS, a focal soft-tissue mass in PVNB or PVNTS, or a normal appearance. Extrinsic erosion of bone (on both sides of the joint) may also be seen and is most frequent with intraarticular involvement of the hip (>90% of cases). Cross-sectional imaging reveals diffuse involvement of the synovium (PVNS), an intimate relationship to the tendon (PVTNS), or a typical bursal location (PVNB), findings that suggest the diagnosis. However, the magnetic resonance (MR) imaging findings of prominent low signal intensity (seen with T2-weighting) and "blooming" artifact from the hemosiderin (seen with gradient-echo sequences) are nearly pathognomonic of this diagnosis. In addition, MR imaging is optimal for evaluating lesion extent. This information is crucial to guide treatment and to achieve complete surgical resection. Recurrence is more common with diffuse intraarticular disease and is difficult to distinguish, both pathologically and radiologically, from the rare complication of malignant PVNS. Recognizing the appearances of the various types of PVNS, which reflect their pathologic characteristics, improves radiologic assessment and is important for optimal patient

  20. Pseudoepitheliomatous hyperplasia: A review of oral lesions

    Directory of Open Access Journals (Sweden)

    P. Premraj

    2016-05-01

    Full Text Available Pseudoepitheliomatous hyperplasia is a histological reactive pattern of surface epithelium in response to various stimuli from the underlying connective tissue which frequently mimics squamous cell carcinoma. So, differentiation of this entity is of utmost important in the view of treatment planning and approach. This review focuses on those lesions which are encountered in the head and neck region and also the recent concepts related to it.

  1. Multilayered pigment epithelial detachment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rahimy, Ehsan; Freund, K Bailey; Larsen, Michael

    2014-01-01

    PURPOSE: To describe the spectral domain optical coherence tomography findings in eyes with chronic fibrovascular pigment epithelial detachment (PED) receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective observational case series of patients...... over a mean of 36.9 months (median, 37.5; range, 6-84). A fusiform, or spindle-shaped, complex of highly organized layered hyperreflective bands was noted within each PED. Nineteen eyes demonstrated heterogenous, dilated, irregular neovascular tissue adherent to the undersurface of the retinal pigment......, hyperreflective bands, termed a "multilayered PED," which is often seen in conjunction with neovascular tissue adherent to the undersurface of the retinal pigment epithelium monolayer. On the basis of previous histopathologic correlations, these bands may represent a fibrous tissue complex with contractile...

  2. Ultrastructure and Glycoconjugate Pattern of the Foot Epithelium of the Abalone Haliotis tuberculata (Linnaeus, 1758 (Gastropoda, Haliotidae

    Directory of Open Access Journals (Sweden)

    I. Bravo Portela

    2012-01-01

    Full Text Available The foot epithelium of the gastropod Haliotis tuberculata is studied by light and electron microscopy in order to contribute to the understanding of the anatomy and functional morphology of the mollusks integument. Study of the external surface by scanning electron microscopy reveals that the side foot epithelium is characterized by a microvillus border with a very scant presence of small ciliary tufts, but the sole foot epithelium bears a dense field of long cilia. Ultrastructural examination by transmission electron microscopy of the side epithelial cells shows deeply pigmented cells with high electron-dense granular content which are not observed in the epithelial sole cells. Along the pedal epithelium, seven types of secretory cells are present; furthermore, two types of subepithelial glands are located just in the sole foot. The presence and composition of glycoconjugates in the secretory cells and subepithelial glands are analyzed by conventional and lectin histochemistry. Subepithelial glands contain mainly N-glycoproteins rich in fucose and mannose whereas secretory cells present mostly acidic sulphated glycoconjugates such as glycosaminoglycans and mucins, which are rich in galactose, N-acetyl-galactosamine, and N-acetyl-glucosamine. No sialic acid is present in the foot epithelium.

  3. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    Science.gov (United States)

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P PRX6 protein expression showed a declining trend with age (P PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

  4. Action spectrum for photochemical retinal pigment epithelium (RPE) disruption in an in vivo monkey model

    Science.gov (United States)

    Zhang, Jie; Sabarinathan, Ranjani; Bubel, Tracy; Williams, David R.; Hunter, Jennifer J.

    2016-03-01

    Observations of RPE disruption and autofluorescence (AF) photobleaching at light levels below the ANSI photochemical maximum permissible exposure (MPE) (Morgan et al., 2008) indicates a demand to modify future light safety standards to protect the retina from harm. To establish safe light exposures, we measured the visible light action spectrum for RPE disruption in an in vivo monkey model with fluorescence adaptive optics retinal imaging. Using this high resolution imaging modality can provide insight into the consequences of light on a cellular level and allow for longitudinal monitoring of retinal changes. The threshold retinal radiant exposures (RRE) for RPE disruption were determined for 4 wavelengths (460, 488, 544, and 594 nm). The anaesthetized macaque retina was exposed to a uniform 0.5° × 0.5° field of view (FOV). Imaging within a 2° × 2° FOV was performed before, immediately after and at 2 week intervals for 10 weeks. At each wavelength, multiple RREs were tested with 4 repetitions each to determine the threshold for RPE disruption. For qualitative analysis, RPE disruption is defined as any detectable change from the pre exposure condition in the cell mosaic in the exposed region relative to the corresponding mosaic in the immediately surrounding area. We have tested several metrics to evaluate the RPE images obtained before and after exposure. The measured action spectrum for photochemical RPE disruption has a shallower slope than the current ANSI photochemical MPE for the same conditions and suggests that longer wavelength light is more hazardous than other measurements would suggest.

  5. In vivo imaging of retinal pigment epithelium cells in age related macular degeneration.

    Science.gov (United States)

    Rossi, Ethan A; Rangel-Fonseca, Piero; Parkins, Keith; Fischer, William; Latchney, Lisa R; Folwell, Margaret A; Williams, David R; Dubra, Alfredo; Chung, Mina M

    2013-01-01

    Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan's method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm(2), which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health.

  6. The Phototoxicity of ’Blue Light’ on the Functional Properties of the Retinal Pigment Epithelium

    Science.gov (United States)

    1990-10-15

    MONITORING AGENCY NAME(S) AND AOORISS(ES) 1. SPONSOPEN /MONITORUNG T. JAN CERVENY, Lt Col, USAF A AFOSR/NL Building 410 Bolling AFB, DC 20332 il...characterization and identity with acidic and basic fibroblast growth factor. Biochemistry 24, 7855-7860. 4. Bazan , N.G., Reddy, T.S., Redmond, T.M., Wiggert, B

  7. ACTA-EVER lecture 2007 - The retinal pigment epithelium: friend or foe?

    DEFF Research Database (Denmark)

    La Cour, Morten

    2008-01-01

    far. We report on a drug delivery system under development where a prodrug of the antimetabolite 5-fluoro-uracil (5-FU) is suspended in the silicone oil used as a surgical device in the treatment of proliferative vitreoretinopathy (PVR). The theoretical advantage of this approach is that it allows...... for long contact times between therapeutic, and non-toxic, concentrations of 5-FU and the RPE Udgivelsesdato: 2008/9...

  8. Inhibition of autophagy suppresses sertraline-mediated primary ciliogenesis in retinal pigment epithelium cells.

    Science.gov (United States)

    Kim, Eun Sung; Shin, Ji Hyun; Park, So Jung; Jo, Yoon Kyung; Kim, Jae-Sung; Kang, Il-Hwan; Nam, Jung-Bum; Chung, Doo-Young; Cho, Yoonchul; Lee, EunJoo H; Chang, Jong Wook; Cho, Dong-Hyung

    2015-01-01

    Primary cilia are conserved cellular organelles that regulate diverse signaling pathways. Autophagy is a complex process of cellular degradation and recycling of cytoplasmic proteins and organelles, and plays an important role in cellular homeostasis. Despite its potential importance, the role of autophagy in ciliogenesis is largely unknown. In this study, we identified sertraline as a regulator of autophagy and ciliogenesis. Sertraline, a known antidepressant, induced the growth of cilia and blocked the disassembly of cilia in htRPE cells. Following treatment of sertraline, there was an increase in the number of cells with autophagic puncta and LC3 protein conversion. In addition, both a decrease of ATG5 expression and the treatment of an autophagy inhibitor resulted in the suppression of the sertraline-induced activation of autophagy in htRPE cells. Interestingly, we found that genetic and chemical inhibition of autophagy attenuated the growth of primary cilia in htRPE cells. Taken together, our results suggest that the inhibition of autophagy suppresses sertraline-induced ciliogenesis.

  9. Retinal pigment epithelium tear formation following intravitreal ranibizumab injection in choroidal neovascularization secondary to choroidal osteoma.

    Science.gov (United States)

    Erol, Muhammet K; Coban, Deniz Turgut; Ceran, Basak Bostanci; Bulut, Mehmet

    2014-09-01

    Choroidal osteoma is an extremely rare osseous tumor of the choroid where choroidal neovascularization (CNV) is the major cause of visual loss. We report the case of a 28-year-old female with CNV secondary to choroidal osteoma, who developed RPE tear after intravitreal ranibizumab treatment.

  10. 21 CFR 178.3725 - Pigment dispersants.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Pigment dispersants. 178.3725 Section 178.3725 Food... regulation, the substances listed in this section may be safely used as pigment dispersants in food-contact... not to exceed 0.45 percent by weight of the pigment. The pigmented articles may contact all...

  11. Salt and Pepper Pigmentation - Skin Manifestation of Systemic Sclerosis.

    Science.gov (United States)

    Vijayaraju, D; Prakash, G; Yoganandh, T; Subramanian, S R; Ramkumar, S

    2015-09-01

    A 50 year old male presented with progressive difficulty in swallowing both liquid and solid food with no history of Raynaud's phenomenon. A general examination revealed skin changes in the form of thickening, hyperpigmentation and tightening of skin of fingers, hand, forearm and legs. The patient had painless skin induration over the legs, forearm and hand. Salt and pepper pigmentation was seen on the upper back (Figure 1a), over mastoid process (Figure 1b) and the concha of pinna (Figure 1c). Anti-Scl 70 was positive. Anti-centromere antibodies were negative. Pulmonary function testing (PFT) revealed very severe restrictive lung disease. Barium swallow study was normal. Despite being advised to undergo oesophageal manometry test in view of dysphagia, patient was not willing for the same. Diagnosis of systemic sclerosis was made. Systemic sclerosis is a disease in which extensive fibrosis, vascular alterations and autoantibodies against various cellular antigens being the principal features with a female to male ratio of 4:1. Skin pigmentation changes among other features of skin involvement include a salt-and-pepper appearance due to diffuse hyperpigmentation with sparing of the perifollicular areas. This may be due to the richer capillary network that may warm the perifollicular skin and preserve melanogenesis producing the perifollicular pigment retention in systemic sclerosis.1,2 Both cellular and humoral immune factors in combination with external factors such as trauma or inflammation may trigger the destruction of melanocytes.3 Moreover, various physical factors like temperature changes as well as genetic, hormonal factors may influence pigment formation. Such changes in pigmentation is also seen during repigmentation around hair follicles in vitiligo. Clinically, both vitiligo and depigmented lesions of systemic sclerosis present as chalk-white macules with well-defined borders. However, mucosal involvement is commonly seen in vitiligo while depigmented

  12. The use of SD-OCT in the differential diagnosis of dots, spots and other white retinal lesions

    Directory of Open Access Journals (Sweden)

    Zaharova E

    2011-10-01

    Full Text Available Elena Zaharova1, Jerome Sherman1-31State University of New York's State College of Optometry, University Eye Center, New York, NY, USA; 2SUNY Eye Institute, New York, NY, USA; 3New York Eye Institute and Laser Center, New York, NY, USAPurpose: To demonstrate the utility of a retinal imaging technique using spectral domain optical coherence tomography (SD-OCT for creating a B-scan layer-by-layer analysis to aid in the differential diagnosis of various retinal dots, spots, and other white lesions.Design: Review.Methods: A retrospective review of imaging studies performed with SD-OCT (Topcon, 3DOCT-2000, Oakland, NJ at SUNY State College of Optometry.Results: B-scan layer-by-layer analysis and unique SD-OCT reflectivity patterns of the following retinal white lesions are reviewed in the order of their retinal layer localization: myelinated nerve fiber layer, cotton wool spot, exudates, edema residues, drusen, fundus albipunctatus, Stargardt disease, Bietti crystalline dystrophy, punctate inner choroidopathy (PIC, presumed ocular histoplasmosis syndrome (POHS, post-photocoagulation chorioretinal scarring, and osseous choristoma.Conclusion: The reviewed images demonstrate the utility of SD-OCT in the identification of the unique characteristics of the presented retinal pathologies. SD-OCT is ideal for retinal layer localization of lesions, thus enhancing the differential diagnosis of retinal dots, spots, and other white lesions. Even though true pathognomonic patterns are rare, highly suggestive findings of certain retinal abnormalities often facilitate immediate recognition and diagnosis.Keywords: SD-OCT, photoreceptor integrity line, retinal pigment epithelium, white dot syndrome, retinal pathology, imaging

  13. A pigmented calcifying odontogenic cyst.

    Science.gov (United States)

    Soames, J V

    1982-04-01

    A case of the pigmented variant of the calcifying odontogenic cyst occurring in a 15-year-old West Indian girl is reported. Melanin pigment was widely distributed and appeared in greatest amount in cells exhibiting the appearance of stellate reticulum. Ultrastructural examination demonstrated large numbers of melanosomes in these cells but relatively few in epithelial ghost cells. The latter contained thick bundles of tonofilaments. Melanocytes were identified and two forms were distinguished, depending on their content of premelanosomes and fully melanized melanosomes.

  14. Analysis of Indian pigment gallstones

    Energy Technology Data Exchange (ETDEWEB)

    Rautray, T.R. [Department of Physics, National Institute of Technology, Rourkela 769 008, Orissa (India)]. E-mail: tapash77@hotmail.com; Vijayan, V. [Institute of Physics, Bhubaneswar 751 005, Orissa (India); Panigrahi, S. [Department of Physics, National Institute of Technology, Rourkela 769 008, Orissa (India)

    2007-02-15

    Particle induced X-ray emission and particle induced {gamma}-ray emission spectroscopic techniques have been carried out to analyse the elemental concentrations of human pigment gallstone samples from eastern region (Orissa) and southern region (Chennai) of India. It was observed that 18 minor/trace elements namely Na, Mg, Al, P, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Br and Pb were present in the pigment gallstone samples of both the regions. Our study reveals that average concentration of all elements except Ni in south Indian pigment gallstone samples is higher than that of corresponding values in east Indian pigment gallstone samples whereas elements like Al, P, S, Cl and V did not show much variation between these two regions. Fourier transform infra-red analysis was carried out to identify the functional groups and the classification of the pigment type gallstones of both the regions. The thermal behaviour of pigment gallstones was carried out by thermogravimetry-derivative thermogravimetry analysis.

  15. Pigments, patterns, and fish behavior.

    Science.gov (United States)

    Price, Anna C; Weadick, Cameron J; Shim, Janet; Rodd, F Helen

    2008-12-01

    Color patterns in fish are often multicomponent signals, composed of pigment-based and structural color patches that can be used to communicate within species, in both inter- and intrasexual interactions, and between species. In this review, we discuss some of the roles played by pigment-based elements of color pattern. We begin by discussing general forms of coloration, classifying them by appearance (e.g., cryptic vs. conspicuous) and apparent function (e.g., conspicuous coloration and mating displays, stripes and cooperation, and bars and aggression). We then briefly discuss the roles pigments play in the perception of these color patterns via their presence in the eye. In the last section, we look at the relative importance of carotenoid versus melanic coloration in situations where honest signals to potential rivals and potential mates might be required. In this survey, we have highlighted some recent research, especially studies that consider both the physiological and behavioral processes underlying the evolution and expression of pigment-based color patterns in fish. The nature of pigmented color patterns depends not just on the dynamics of pattern development and physiological regulation, but also on the behavioral roles played by these patterns, both now and in the past. As such, advances in particular fields of study on pigment patterns (physiology, developmental biology, behavioral ecology, evolutionary biology, etc.) will increasingly depend on insights from other fields.

  16. Parasellar lesions

    Energy Technology Data Exchange (ETDEWEB)

    Ruscalleda, J. [Hospital Sant Pau, Radiology Department, Neuroradiology, Barcelona (Spain)

    2005-03-01

    The sellar and parasellar region is an anatomically complex area that represents a crucial crossroad of important adjacent structures, e.g. orbits, cavernous sinus and its content, polygon of Willis, hypothalamus through the pituitary stalk and dural reflections forming the diaphragm sellae and the walls of the cavernous sinuses. Although the cavernous sinus represents the most relevant parasellar structure, from the practical and clinical point of view all the structures that surround the sella turcica can be included in the parasellar region. CT and, mainly, MRI are the imaging modalities to study and characterise the normal anatomy and the majority of processes in this region. We present a practical short review of the most relevant CT and MRI characteristics, such as location, nature of contrast enhancement and presence of cystic components, together with clinical findings, which permit differentiation of the most frequent and less common lesions found in the parasellar region. Learning objectives: A short review of the anatomy and clinical symptoms related to the parasellar region. Radiological characterisation, mainly by MRI, of the many lesions that alter the structure and function of sellar and parasellar anatomy. Description of the MRI features that permit differentiation among less common lesions. (orig.)

  17. Multilayered epithelium at the gastroesophageal junction is a marker of gastroesophageal reflux disease: data from a prospective Central European multicenter study (histoGERD trial).

    Science.gov (United States)

    Langner, Cord; Wolf, Eva-Maria; Plieschnegger, Wolfgang; Geppert, Michael; Wigginghaus, Bernd; Höss, Gabriele M; Eherer, Andreas; Schneider, Nora I; Rehak, Peter; Vieth, Michael

    2014-04-01

    Multilayered epithelium is defined as hybrid epithelium with characteristics of both squamous and columnar epithelia. Our aim was to evaluate the clinicopathological significance of the lesion by relating its presence to various histological and clinical and/or endoscopic features indicating gastroesophageal reflux disease (GERD). A total of 1,071 individuals participated in a prospective cross-sectional study (576 females and 495 males; median age 53 years). Biopsy material was systematically sampled from the gastroesophageal junction. The histological diagnosis of esophagitis was made according to the Esohisto consensus guidelines. The endoscopic diagnosis of esophagitis was made according to the modified Los Angeles classification and the diagnosis of Barrett's esophagus according to Prague's C & M criteria, respectively. Multilayered epithelium was identified in 103 (9.6 %) individuals, frequently within or adjacent to the ducts of esophageal glands. Its presence was associated with increasing age (p epithelium was associated with features of the squamous epithelium indicating GERD, particularly intercellular space dilation (p = 0.005), and presence of cardiac mucosa (epithelium was observed in about every tenth individual undergoing upper gastrointestinal endoscopy. The association with histological and clinical features indicating GERD advocates the lesion as a promising new marker for reflux esophagitis. The association with cardiac mucosa and Barrett's esophagus suggests multilayered epithelium to be an intermediate step in the development of columnar metaplasia and, ultimately, Barrett's esophagus.

  18. Approximate Lesion Localization in Dermoscopy Images

    CERN Document Server

    Celebi, M Emre; Schaefer, Gerald; Stoecker, William V; 10.1111/j.1600-0846.2009.00357.x

    2010-01-01

    Background: Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity of human interpretation, automated analysis of dermoscopy images has become an important research area. Border detection is often the first step in this analysis. Methods: In this article, we present an approximate lesion localization method that serves as a preprocessing step for detecting borders in dermoscopy images. In this method, first the black frame around the image is removed using an iterative algorithm. The approximate location of the lesion is then determined using an ensemble of thresholding algorithms. Results: The method is tested on a set of 428 dermoscopy images. The localization error is quantified by a metric that uses dermatologist determined borders as the ground truth. Conclusion: The results demonstrate that the method presented here achieves both fast and accurate localization of lesions in dermoscopy images.

  19. Oral mucosa lesions in Mazahua Indian adolescents.

    Science.gov (United States)

    Banderas, J A; Toshikasu, O; González, M

    1999-01-01

    The epidemiologic data on oral lesions in native Indians remain unknown in many countries around the world. This paper reports the prevalence and distribution of oral congenital anomalies and pathologic lesions found in a survey of 107 schoolchildren (ages 12 to 17), from two isolated communities in the ethnographic Mazahua area in the State of Mexico. The main entities identified were: pigmented lesions (47.6%), lingual anomalies (17.4%) and developmental tooth alterations (6.9%). The remaining 24.4% of the lesions were gingival inflammatory hyperplasia, partial ankilosis of the tongue, lichen planus, focal epithelial hyperplasia and the double lip. The most frequent localization was lips and tongue. These findings suggest the high prevalence of oral anomalies in this Indian population. Therefore, we suggest that health programs should emphasize the prevention, diagnosis and treatment of these pathologies in Indians groups.

  20. Unusual finding of endocervical-like mucinous epithelium in continuity with urothelium in endocervicosis of the urinary bladder.

    Science.gov (United States)

    Cheah, Phaik-Leng; Looi, Lai-Meng; Lee, George Eng-Geap; Teoh, Kean-Hooi; Mun, Kein-Seong; Nazarina, Abdul Rahman

    2011-06-23

    Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion.

  1. Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.

    Science.gov (United States)

    Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko

    2013-05-01

    It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

  2. Hemosiderotic clear-cell acanthoma: A pigmented mimicker

    Directory of Open Access Journals (Sweden)

    Leonardo Bugatti

    2011-01-01

    Full Text Available The authors report on a case of a 65-year-old man with pigmented clear-cell acanthoma located on the right thigh. Dermoscopy disclosed a peculiar picture consisting of diffuse black pigmentation with a superficial greyish veil in the central portion, dotted-to-globular dark red-black structures mainly located at the periphery with a homogenous regular reticular arrangement; peripheral translucid desquamation. Dermoscopic features are correlated with the histology, where hemosiderin deposits present in a sheet-like arrangement in the perivascular papillary dermis and in a band-like disposition in the reticular dermis at the base of the lesion can account for the pigmented picture. The lesion arose on a trauma-prone skin site; thus the authors believe that traumatic irritation may be responsible for the clinical and dermoscopic pictures, giving rise to a reaction similar in a way to the Auspitz′s sign provocated by trauma for psoriasis. Red blood cells extravasation from extremely superficialized capillaries may have led to hemosiderin deposition in the papillary and the reticular dermis.

  3. [Congenital "kissing" lesions: Nevus or "café au lait" spot?

    Science.gov (United States)

    Durazzo, A; Boccara, O; Fraitag, S; Fusade, T; Picard, A; Kadlub, N

    2016-12-01

    "Café au lait" spots (CLS) are pigmented skin lesions principally located at the trunk and the limbs. Histologically, CLSs consist in an excessive pigmentation of the epidermis, with no risk of malignant transformation. The "kissing" nevus is a rare pigmented congenital nevus affecting both lower and upper eyelids in a mirror layout. As other nevi, it presents a theoretical risk of malignant transformation. These two pigmented lesions are responsible for aesthetic discomfort when affecting the face. Three patients presenting with a congenital pigmented lesion affecting the two eyelids in a mirror layout are presented. In two cases, the lesions, initially considered as "kissing" nevi, were classified as CLSs. The diagnosis of CLS was made on a biopsy in one patient and after surgery in the other one. Pigmented mirror layout lesions, called "kissing" lesions, are exclusively described for the nevi. We describe two cases of CLSs affecting the eyelids in a mirror layout. Difficulties in diagnostic are exposed and the possible treatments are discussed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Pigmented Villonodular Synovitis in a Patient who Underwent Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Nevzat Dabak

    2014-09-01

    Full Text Available Pigmented villonodular synovitis (PVNS is a rare, benign, but a locally aggressive tumor. It is characterized by the proliferation of synovial membrane, but it can also be seen in tendon sheaths and bursae. Clinical presentation of solitary lesions include compression and locking of the joint suggesting loose bodies in the joint and a subsequent findings of an effusion, whereas diffuse lesions manifest with pain and chronic swelling. In this article, we presented a curious case of PVNS in a female patient who have been followed up due to an acetabular cystic lesion. She underwent total hip arthroplasty for severe osteoarthritis of the hip joint and associated pain. The diagnosis of PVNS was established intraoperatively. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 235-7

  5. Heterogeneity of the intrahepatic biliary epithelium

    Institute of Scientific and Technical Information of China (English)

    Shannon Glaser; Heather Francis; Sharon DeMorrow; Gene LeSage; Giammarco Fava; Marco Marzioni; Julie Venter; Gianfranco Alpini

    2006-01-01

    The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCl4) or α-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.

  6. 骨形成蛋白(BMP)-2/4,-5与IA型BMP受体在口腔正常上皮、良性病变及癌变中的表达分析%EXPRESSIONS OF BMP-2/4,-5 and BMPR-IA RECEPTOR IN NORMAL, BENIGN AND MALIGNANT LESIONS OF ORAL EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The aim of the present study was investigate the relationshipsbetween bone morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral epithelia. Expressions of BMP-2/4,-5 and BMPR-IA were analyzed in the specimens obtained from buccal mucosa, including 9 cases of normal mucosa (NB), 8 cases of chronic inflammation (NCI), 7 cases of hyperkeratosis (HK), 5 cases of squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC), 10 cases of epithelium adjacent to carcinoma (EAC) and 6 cases of normal mucosa from hard palate (NHP) by using immunohistochemistry. Results demonstrated that the immunostaining of BMP-2/4,BMP-5 and BMPR-IA was weak and not consistent in normal and benign groups. Except for 3 cases of SCC, all cases of SCC showed positive staining for BMP-2/4, BMP-5 and BMPR-IA. The staining intensity and proportion of the positively stained cells in SCC were markedly increased than in normal and benign groups except for EAC. The metastatic carcinoma cells in lymph nodes were strongly and positively stained for BMP-2/4,BMP-5 and BMPR-IA might be involved in the carcinogenesis of oral epithelia.%认识BMP及其受体与口腔正常上皮及其癌变的关系,有助于深入了解口腔上皮癌变的机理。本文用免疫组织化学方法对BMP-2/4,-5与BMP受体BMPR-IA在口腔颊部粘膜正常上皮、良性病变和癌变中的表达进行观察和半定量分析。标本包括:9例正常上皮(normalbuccal mucosa, NB)、8例慢性炎症(nonspecific chronic inflammation,NCI)、7例过度角化(hyperkeratosis, HK)、5例乳头状瘤(squamous cell papilloma,SCP)、29例鳞癌(squamous cell carcinoma,SCC)、10例癌旁上皮(epithelium immediately adjacent to carcinoma,EAC)以及6例硬腭粘膜上皮(normal mucosa of hard palate,NHP)。结果显示:BMP-2/4,-5与BMPR-IA在口腔粘膜的正常与良性病变上皮中有弱的和不均一的阳性表达,NB与NHP无明显差别。而除3例SCC外,其它SCC

  7. Tannic acid binding of cell surfaces in normal, premalignant, and malignant squamous epithelium of the human uterine cervix.

    Science.gov (United States)

    Davina, J H; Lamers, G E; van Haelst, U J; Kenemans, P; Stadhouders, A M

    1984-01-01

    Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

  8. Columnar cell lesions of the breast: clinical significance and molecular background

    NARCIS (Netherlands)

    Verschuur-Maes, A.H.J.

    2012-01-01

    Columnar cell lesions (CCLs) of the breast have since long been regarded as possible precursor lesions of breast cancer. CCLs are cystically dilated ducts lined by columnar cell epithelium, with or without atypia. Intraluminal secretions and microcalcifications are frequently seen and the microcalci

  9. Pigmented villonodular synovitis of the thoracic spine.

    Science.gov (United States)

    Roguski, Marie; Safain, Mina G; Zerris, Vasilios A; Kryzanski, James T; Thomas, Christine B; Magge, Subu N; Riesenburger, Ron I

    2014-10-01

    Pigmented villonodular synovitis (PVNS) is a proliferative lesion of the synovial membranes. Knees, hips, and other large weight-bearing joints are most commonly affected. PVNS rarely presents in the spine, in particular the thoracic segments. We present a patient with PVNS in the thoracic spine and describe its clinical presentation, radiographic findings, pathologic features, and treatment as well as providing the first comprehensive meta-analysis and review of the literature on this topic, to our knowledge. A total of 28 publications reporting 56 patients were found. The lumbar and cervical spine were most frequently involved (40% and 36% of patients, respectively) with infrequent involvement of the thoracic spine (24% of patients). PVNS affects a wide range of ages, but has a particular predilection for the thoracic spine in younger patients. The mean age in the thoracic group was 22.8 years and was significantly lower than the cervical and lumbar groups (42.4 and 48.6 years, respectively; p=0.0001). PVNS should be included in the differential diagnosis of osteodestructive lesions of the spine, especially because of its potential for local recurrence. The goal of treatment should be complete surgical excision. Although the pathogenesis is not clear, mechanical strain may play an important role, especially in cervical and lumbar PVNS. The association of thoracic lesions and younger age suggests that other factors, such as neoplasia, derangement of lipid metabolism, perturbations of humoral and cellular immunity, and other undefined patient factors, play a role in the development of thoracic PVNS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Pigmented villonodular synovitis mimics metastases on fluorine 18 fluorodeoxyglucose position emission tomography-computed tomography.

    Science.gov (United States)

    Elumogo, Comfort O; Kochenderfer, James N; Civelek, A Cahid; Bluemke, David A

    2016-04-01

    Pigmented villonodular synovitis (PVNS) is a benign joint disease best characterized on magnetic resonance imaging (MRI). The role of fluorine 18 fluorodeoxyglucose ((18)F-FDG) position emission tomography-computed tomography (PET-CT) in the diagnosis or characterization remains unclear. PVNS displays as a focal FDG avid lesion, which can masquerade as a metastatic lesion, on PET-CET. We present a case of PVNS found on surveillance imaging of a lymphoma patient.

  11. PIGMENTED VILLONODULAR SYNOVITIS IN A RETICULATED GIRAFFE (GIRAFFA CAMELOPARDALIS).

    Science.gov (United States)

    Ihms, Elizabeth A; Rivas, Anne; Bronson, Ellen; Mangus, Lisa M

    2017-06-01

    : A 17-yr-old, female, captive-born reticulated giraffe ( Giraffa camelopardalis ) presented with acute-onset lameness of the right metacarpophalangeal (fetlock) joint. Despite multiple courses of treatment, the lameness and swelling progressively worsened over a 3.5-yr period, and the giraffe was euthanized. At necropsy, gross and microscopic changes in the right, front fetlock and associated flexor tendon sheath included villous synovial hyperplasia and the formation of discrete pigmented nodules within synovial membranes. Histologically, the nodules were composed of abundant, fibrous connective tissue with heavy macrophage infiltration, hemosiderin deposition, and distinctive, multinucleated cells that resembled osteoclasts. These findings were consistent with pigmented villonodular synovitis (PVNS), a rare condition affecting both humans and animals. Although the pathophysiology of PVNS is poorly understood, lesions exhibit features of both neoplastic and reactive inflammatory processes. This case report represents, to the authors' knowledge, the first description of PVNS in a nondomestic ungulate.

  12. A Rare Cause of Mucocutaneous Pigmentation: Laugier Hunziker Syndrome

    Directory of Open Access Journals (Sweden)

    Gonca Meriç

    2011-11-01

    Full Text Available Laugier Hunziker syndrome (LHS is a rare, acquired pigmentation disorder characterized by macular melonotic pigmentation of the oral mucous membranes and lips frequently associated with longitudinal melanonychia. LHS is known to be an entirely benign condition with no underlying systemic abnormalities or malignant predisposition. However, it is very important to make a differential diagnosis with other mucocutaneous pigmentary disorders which require detailed examination, treatment and follow up. LHS is seen very rarely and to our knowledge, approximately 100 cases have been described in the literature, to date. There are only seven cases reported from the our country, based on the literature search in PubMed and Turkish Dermatological journals, avaliable on the web. Herein we report a 54-year-old woman diagnosed as having LHS, with hyperpigmented macular lesions of the tongue, lip, buccal mucosa, gingiva and palms and soles.

  13. Pigmented purpuric dermatosis or mycosis fungoides: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Najeeba Riyaz

    2016-01-01

    Full Text Available Pigmented purpuric dermatoses (PPD, a group of vascular disorders with variable clinical picture is reported in all races and age groups with a male predilection. There are reports of mycosis fungoides manifesting as pigmented purpura as well as progression of PPD to cutaneous T-cell lymphoma. The diagnostic dilemma is compounded by PPD manifesting histological similarity to mycosis fungoides. Currently, it is believed that PPD with monoclonal T-cell population is more likely to progress to malignancy. We report a 31-year-old male patient who presented with the lichenoid clinical variant of PPD lesions that mimicked mycosis fungoides on histopathology. Gene rearrangement studies identified a polyclonal T-cell population. The patient responded to photochemotherapy, which is beneficial in both PPD and mycosis fungoides. Our case signifies the limitations of current diagnostic modalities in accurately distinguishing PPD from cutaneous lymphoma. Data on disease progression in similar cases may enable us to formulate better diagnostic definitions.

  14. Prevalence of oral mucosal lesions in patients of the Kuwait University Dental Center.

    Science.gov (United States)

    Ali, Mohammad; Joseph, Bobby; Sundaram, Devipriya

    2013-07-01

    The purpose of this study was to determine the number, types, and locations of oral mucosal lesions in patients who attended the Admission Clinic at the Kuwait University Dental Center to determine prevalence and risk factors for oral lesions. Intraoral soft tissue examination was performed on new patients seen between January 2009 and February 2011. The lesions were divided into six major groups: white, red, pigmented, ulcerative, exophytic, and miscellaneous. Five hundred thirty patients were screened, out of which 308 (58.1%) had one or more lesions. A total of 570 oral lesions and conditions were identified in this study, of which 272 (47.7%) were white, 25 (4.4%) were red, 114 (20.0%) were pigmented, 21 (3.7%) were ulcerative, 108 (18.9%) were exophytic, and 30 (5.3%) were in the miscellaneous group. Overall, Fordyce granules (n = 116; 20.4%) were the most frequently detected condition. A significantly higher (p lesions than those in the ⩽20 years age group. A significantly higher (p lesions than did nonsmokers. Most of the lesions and conditions were found on the buccal mucosa and gingiva. White, pigmented, and exophytic lesions were the most common types of oral mucosal lesions found in this study. Although most of these lesions are innocuous, the dentist should be able to recognize and differentiate them from the worrisome lesions, and decide on the appropriate treatment.

  15. Quantification of PCNA+ cells within odontogenic jaw cyst epithelium.

    Science.gov (United States)

    Li, T J; Browne, R M; Matthews, J B

    1994-04-01

    The aim of this study was to investigate the reactivity of the epithelial linings of the three major types of odontogenic cyst with a monoclonal antibody to proliferating cell nuclear antigen (PCNA; clone PC10). PCNA expression was studied in odontogenic cysts (n = 31) and normal oral epithelium (n = 10) using a biotin-streptavidin method on routinely processed paraffin sections. PCNA+ cells were counted manually and related to the length of basement membrane (mm) and the epithelial area (mm2) as determined by TV image analysis. The epithelial linings of odontogenic keratocysts (OKC; n = 11) contained the highest number of PCNA+ cells, most of which were located in the suprabasal layers. The mean value of PCNA+ cells in OKC linings (94.4 +/- 22.7 cells/mm) was similar to that of oral epithelia (80.8 +/- 20.6 cells/mm), but both were significantly higher than that of dentigerous (n = 10, 5.1 +/- 3.0 cells/mm) and radicular (n = 10, 11.0 +/- 4.1 cells/mm) cyst linings (P < 0.005). The epithelial distribution of PCNA+ cells differed between groups with the basal/suprabasal PCNA+ cell ratio in OKC linings (0.05 +/- 0.02) being significantly lower than that of normal oral epithelium (0.5 +/- 0.14), dentigerous (1.6 +/- 1.23) and radicular (1.9 +/- 1.09) cyst linings respectively (P < 0.005). These results demonstrate differences in PCNA expression between the epithelial linings of the major odontogenic cyst types, indicating differences in proliferative and differentiation processes within these lesions.

  16. Pigmented hepatocellular adenoma with complete CD34 immunostaining pattern: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Mukul Vij

    2012-01-01

    Full Text Available WHO defines hepatocellular adenoma (HCA as a benign tumor composed of cells closely resembling normal hepatocytes, which are arranged in plates separated by sinusoids. It is more common in women. The present concerns a 41 years female who was found to have a mass lesion in liver on ultrasound while undergoing routine evaluation for dyspepsia. Computed tomography scan of abdomen showed 10 × 8 cm lesion in liver. Extended left hepatectomy was performed. Grossly hepatic cut surface showed circumscribed tumor with dark gray or black color. Microscopy revealed hepatocellular adenoma with abundant Dubin Johnson like pigment deposition. CD34 immunostaining showed complete sinusoidal pattern. We labeled the tumor as pigmented hepatic adenoma with complete CD34 staining pattern. To the best of author′s knowledge only eight cases of pigmented hepatocellular adenoma are described in world literature.

  17. Clinicoepidemiological study of pigmented purpuric dermatoses

    Directory of Open Access Journals (Sweden)

    Lata Sharma

    2012-01-01

    Full Text Available Background: Pigmented purpuric dermatoses (PPD are a group of vascular disorders with varied manifestations which cause concern and are resistant to treatment. The literature is still lacking in clinicoepidemiological studies. Aim: To study the epidemiology, etiological, host and environmental factors, clinical manifestations, its variations, and the type prevalent in this part of the world. Materials and Methods: All cases of PPD were selected for the study from Skin and Venereal Disease, Out Patient Department between January 2008 and June 2009. Their history, examination, hematological investigations, and, in a few, histopathology findings were also recorded and data obtained were evaluated statistically. Results: There were 100 cases of PPD of total 55 323 patients (0.18%. There were 79 males and 21 females between 11 and 66 years. They were working as police men, security guards, barber, chemist, teachers, students, farmers, businessmen, and housewives. In a majority, there was a history of prolonged standing in day-to-day work. Purpuric, brownish pigmented, lichenoid or atrophic lesions were seen depending upon the type of PPD on lower parts of one or both lower limbs. Blood investigations were normal. Schamberg′s disease was seen in ninety five, Lichen aureus in three, lichenoid dermatosis and Majocchi′s disease in one case each. Discussion: Three clinical types of PPD were diagnosed which may represent different features of the same disease. Cell-mediated immunity, immune complexes, capillary fragility, gravitational forces, venous hypertension, focal infection, clothing, contact allergy to dyes, and drug intake have been incriminating factors in the past. Patient′s occupation and environmental factors may also be considered contributory in precipitating the disease. Conclusions: The study revealed the problem of PPD in this geographical area, its magnitude, clinical presentation, the type prevalent, and possible aggravating

  18. Accuracy of pulse oximetry in pigmented patients

    African Journals Online (AJOL)

    Reflectance was measured at nine wavelengths. Results. The degree of pigmentation as measured by ... adversely affected by skin pigmentation, and it remains a ... the inner surface of the upper arm and the volar aspect of ..... Ph.D. mesis.

  19. Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

    Science.gov (United States)

    Danielsson, Karin; Coates, Philip J; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2014-09-01

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

  20. Yap and Taz regulate retinal pigment epithelial cell fate

    Science.gov (United States)

    Miesfeld, Joel B.; Gestri, Gaia; Clark, Brian S.; Flinn, Michael A.; Poole, Richard J.; Bader, Jason R.; Besharse, Joseph C.; Wilson, Stephen W.; Link, Brian A.

    2015-01-01

    The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Tead-responsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap-dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma. PMID:26209646

  1. [Classification signs of end-stage pigmented retinitis].

    Science.gov (United States)

    Zhukova, S I; Shchuko, A G; Malyshev, V V

    2007-01-01

    Identification of objective criteria for early-stage pigmented retinitis (PR) remains urgent today. Visual system changes reflecting retinal metabolic and structural disturbances (a change in the time and amplitude parameters of ERG, an increase in dark adaptation, changes in the color palette and the thickness of layers of photoreceptors and pigment epithelium of the retina on the OST scans) were detected in 31% of the examined relatives of patients with PR. The authors show the diagnostic value of retinal optic coherent tomography in the diagnosis of PR and the expediency of its use for objective estimation of retinal structural changes along with functional studies. The statistical studies including descriptive, regression, and discriminant analyses have provided evidence that the characteristics of the visual system in patients with end-stage PR differ from those in the controls. Studies that can determine differences in the state of the visual system of the groups under study and significantly discriminate persons with the normally functioning visual system from patients with PR have been identified.

  2. Clofazimine-induced Hair Pigmentation

    Science.gov (United States)

    Philip, Mariam; Samson, Joan Felicita; Simi, Puthenveedu Salahudeen

    2012-01-01

    A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy. PMID:23180930

  3. Clofazimine-induced Hair Pigmentation.

    Science.gov (United States)

    Philip, Mariam; Samson, Joan Felicita; Simi, Puthenveedu Salahudeen

    2012-07-01

    A 45-year-old man was treated with WHO multibacillary multidrug therapy for borderline leprosy and high dose daily Clofazimine for lepra reaction. Along with the expected side effect of skin pigmentation, the patient also noticed darkening of previously grey hair. This colour persisted eight months after completing multibacillary multidrug therapy.

  4. Primary pigmented nodular adrenocortical disease

    Directory of Open Access Journals (Sweden)

    Marie T Manipadam

    2011-01-01

    Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of ACTH-independent Cushing′s syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney′s complex. Bilateral adrenalectomy is the treatment of choice.

  5. Prostaglandin E2 release from dermis regulates sodium permeability of frog skin epithelium

    DEFF Research Database (Denmark)

    Rytved, Klaus A.; Brodin, Birger; Nielsen, Robert

    1995-01-01

    Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium.......Arachidonic acid, cAMP, epithelium, frog skin, intracellular calcium, prostaglandin E*U2, sodium transport, tight epithelium....

  6. [Neutrophils and monocytes in gingival epithelium

    Science.gov (United States)

    Meng, H X; Zheng, L P

    1994-06-01

    Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival bacteria were quantitated and analyzed,The results showed that the numbers of PMN within either pocket epithelium or oral gingival epithelium in JP were significantly lower than in AP and G.The amounts of PMN in AP were much larger than other three groups.Positive correlation between the number of PMN in sulcular pocket epitelium and the motile bacteri of subgingival plaque was demonstrated by correlation analysis.Monocytes mainly presented in deep pocket and junctional epithelum which were stained by NAE method,however very few Langhans cells were seen in these areas.

  7. Lung alveolar epithelium and interstitial lung disease.

    Science.gov (United States)

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  8. Intestinal epithelium in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Mehmet eCoskun

    2014-08-01

    Full Text Available The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs that are crucial in maintaining intestinal homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course of inflammatory bowel disease (IBD. Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets.

  9. Intestinal epithelium in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet

    2014-01-01

    The intestinal epithelium has a strategic position as a protective physical barrier to luminal microbiota and actively contributes to the mucosal immune system. This barrier is mainly formed by a monolayer of specialized intestinal epithelial cells (IECs) that are crucial in maintaining intestinal...... homeostasis. Therefore, dysregulation within the epithelial layer can increase intestinal permeability, lead to abnormalities in interactions between IECs and immune cells in underlying lamina propria, and disturb the intestinal immune homeostasis, all of which are linked to the clinical disease course...... of inflammatory bowel disease (IBD). Understanding the role of the intestinal epithelium in IBD pathogenesis might contribute to an improved knowledge of the inflammatory processes and the identification of potential therapeutic targets....

  10. Mechanically patterning the embryonic airway epithelium

    Science.gov (United States)

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  11. Odors Discrimination by Olfactory Epithelium Biosensor

    Science.gov (United States)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  12. A Quantitative Evaluation Of Epithelium And Inflammatory Infiltrate Of Lichen Planus And Lichenoid Reactions

    Directory of Open Access Journals (Sweden)

    Maji Jose

    2012-07-01

    Full Text Available Lichen planus and Lichenoid reaction are two different entities that pose adiagnostic dilemma. Objectives: Lichen planus and Lichenoid reactions are clinically andhistopathologically very similar but have different treatment and prognosis. This particularstudy is aimed at differentiating both these entities histopathologically with the use ofmicrometry and to find the role of subepithelial chronic inflammatory infiltrate onoverlying epithelium with regard to its thickness.Methods: In the present study, Lichen Planus (n=30 and Lichenoid reactions (n=10 werestudied. Using eyepiece graticule, epithelial thickness and subepithelial inflammatory bandthickness were measured in these lesions.Results: Positive correlation was seen between epithelial and inflammatory band thicknessin cases of lichenoid reactions and a negative correlation in cases of lichen planus.Conclusion: The study suggests that the nature and thickness of subepithelial infiltrate hasan influence on the overlying epithelium in Lichen Planus and Lichenoid reaction.

  13. Pigmentation associated histopathological variations in sympathetic ophthalmia.

    Science.gov (United States)

    Marak, G E; Ikui, H

    1980-01-01

    The severity of inflammation in sympathetic ophthalmia is related to the degree of pigmentation, and the granulomatous response seems to be related to pigmentation. Eosinophilia is also associated with pigmentation, but this association appears to be fortuitous and is a result of the association of eosinophilia with severity of the inflammation. PMID:7387955

  14. 21 CFR 73.352 - Paracoccus pigment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Paracoccus pigment. 73.352 Section 73.352 Food and... ADDITIVES EXEMPT FROM CERTIFICATION Foods § 73.352 Paracoccus pigment. (a) Identity. (1) The color additive... mixtures for coloring foods. (b) Specifications. Paracoccus pigment shall conform to the...

  15. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  16. Effect of hydrogen fluoride on two pigments in coleus

    Energy Technology Data Exchange (ETDEWEB)

    Lamprecht, W.O. Jr.; Powell, R.D.

    Coleus blumei Benth. Cv. 12th Man was fumigated with hydrogen fluoride gas. The treatment caused the development of lesions which originally involved the mesophyll but spread to and eventually included the epidermis. An anthocyanin, cyanidin-3,5-diglucoside acylated with p-coumaric acid, was destroyed and it was postulated that the flavanonol, dihydrokaempferol, was converted to the flavone, apigenin. The anthocyanin destruction and pigment conversion occurred following membrane injury and mixing of the cellular constituents. 17 references, 1 figure, 1 table.

  17. Target-like pigmentation after minipunch grafting in stable vitiligo

    Directory of Open Access Journals (Sweden)

    Nelee Bisen

    2014-01-01

    Full Text Available Surgical treatment for vitiligo has been ever evolving. Each surgical modality has its own benefits and limitations. Miniature punch grafting is the most extensively performed surgery, which gives good results in stable vitiligo. Herein we report an unusual type of repigmentation observed after minipunch grafting in a patient of stable vitiligo, which resembled target-like lesions with a "perigraft halo" surrounding individual grafts. Such pigment spread occurred despite the use of 0.5 mm larger graft from the donor site.

  18. Osteochondral destruction in pigmented villonodular synovitis during the clinical course.

    Science.gov (United States)

    Nishida, Yoshihiro; Tsukushi, Satoshi; Nakashima, Hiroatsu; Sugiura, Hideshi; Yamada, Yoshihisa; Urakawa, Hiroshi; Arai, Eisuke; Ishiguro, Naoki

    2012-02-01

    In pigmented villonodular synovitis (PVNS), some cases recur and progress to osteochondral destruction. The aim of our study was to clarify the occurrence of osteochondral destruction according to the location of PVNS during the clinical course. Seventy-two patients with PVNS (43 female, 29 male) with a mean age of 40 years (range 3-87 yrs) had been referred to our institutions. Factors influencing the occurrence of osteochondral destruction were investigated. Mean followup was 60 months (range 12-190 mo). Adjacent bone change occurred in 24 (42%) of 57 patients, who were evaluated at the time of the first consultation. Eight (89%) of 9 patients with hip lesions initially had bone lesions, significantly more frequently than those with other lesions (p = 0.038). Duration of symptoms was significantly correlated with the occurrence of bone lesions in diffuse knee lesions (p = 0.005). During followup, patients with location in the knee had a significantly higher incidence of osteoarthritic change (73%) compared to those with foot and ankle involvement (p = 0.027). Re-operation was more frequently required for knee lesions due to the high recurrence rate (32%). Patients who required re-operation had significantly more marked osteoarthritic change in knees (p = 0.001) during followup than those who did not. For PVNS arising in knees, repeated recurrences followed by re-operation resulted in the progression of osteoarthritic change. PVNS arising in hips, feet, and ankles developed bone lesions initially, probably due to the limited volume of these joints. The indications for re-operation for recurrent knee lesions require careful consideration regarding progression of osteoarthritic change.

  19. Histopathologic and Immunohistochemical Correlates of Confocal Descriptors in Pigmented Facial Macules on Photodamaged Skin.

    Science.gov (United States)

    Gómez-Martín, Ignacio; Moreno, Sara; Andrades-López, Evelyn; Hernández-Muñoz, Inma; Gallardo, Fernando; Barranco, Carlos; Pujol, Ramon M; Segura, Sonia

    2017-08-01

    Pigmented facial macules on photodamaged skin are a clinical, dermoscopic, and histopathologic challenge. To clinically and dermoscopically characterize, by means of reflectance confocal microscopy (RCM), ambiguous pigmented facial macules and establish a correlation between RCM, histopathologic, and immunohistochemical findings. A prospective study of ambiguous pigmented facial macules on photodamaged skin was conducted in a tertiary referral center for dermatology between January 1, 2009, and December 31, 2015. Sixty-one patients with 63 ambiguous pigmented facial macules and 12 control photodamaged facial areas were included in the study. Melanocyte density in 1-mm basal layers was determined in skin biopsy specimens from all lesions stained with hematoxylin-eosin and immunohistochemical markers (melan-A, microphthalmia-associated transcription factor, and SRY-related HMG-box gene 10). Dermoscopic, RCM images, and histopathologic preparations were systematically evaluated for the presence of lentigo maligna (LM) criteria. Confocal evaluation was blinded to clinical and dermoscopic diagnosis. Sensitivity and specificity of RCM for LM diagnosis and κ value to establish correlations between dermoscopy, RCM, and histopathology were performed. Sensitivity and specificity of RCM for LM diagnosis. Of the 61 patients included in the study, 31 (51%) were women; mean (SD) age was 71.8 (13.1) years. Twenty-four of the 63 (38%) lesions were diagnosed as LM or LM melanoma (LMM) and 39 (62%) as benign pigmented lesions. Reflectance confocal microscopy enhanced the diagnosis of pigmented facial macules with 91.7% sensitivity and 86.8% specificity. Multivariate analysis showed 2 dermoscopic and 2 confocal features associated with LM or LMM: (1) asymmetric follicular pigmentation and targetlike structures, and (2) round, large pagetoid cells and follicular localization of atypical cells, respectively. Continuous proliferation of atypical melanocytes was found in 21 (88%) LM or

  20. Hybrid pigment organelles in an invertebrate.

    Science.gov (United States)

    Schliwa, M; Euteneuer, U

    1979-02-28

    Observations of a number of vertebrate chromatophores have revealed the presence of more than one type of pigment organelles, suggesting that the different types are all derived from an equipotential organelle able to differentiate into any of the major pigment-containing organelles (Bagnara, 1972). Observations are presented concerning the occurrence of hybrid pigment inclusions, i.e., all kinds of intergrades between melanosomes, pterinosomes, and reflecting platelets in pigment cells of the daddy-long-legs. It therefore seems possible that pigment organelles in some invertebrates may also be derived from a common pluripotential primordial organelle.

  1. Papillomavirus associated skin lesions in a cat seropositive for feline immunodeficiency virus

    NARCIS (Netherlands)

    Horzinek, M.C.; Egberink, H.F.; Berrocal, A.; Bax, H.A.; Ingh, T.S.G.A.M. van den; Walter, J.H.

    1992-01-01

    A cat was presented with skin lesions consisting of slightly raised pigmented plaques, 2 7 mm in diameter with a rough slightly verrucous surface. Histologically these lesions were identified as papillomas. A papillomavirus infection was demonstrated: virus-like particles were present in the nuclei

  2. Papillomavirus associated skin lesions in a cat seropositive for feline immunodeficiency virus

    NARCIS (Netherlands)

    Horzinek, M.C.; Egberink, H.F.; Berrocal, A.; Bax, H.A.; Ingh, T.S.G.A.M. van den; Walter, J.H.

    1992-01-01

    A cat was presented with skin lesions consisting of slightly raised pigmented plaques, 2 7 mm in diameter with a rough slightly verrucous surface. Histologically these lesions were identified as papillomas. A papillomavirus infection was demonstrated: virus-like particles were present in the nuclei

  3. Repair of tracheal epithelium by basal cells after chlorine-induced injury

    Directory of Open Access Journals (Sweden)

    Musah Sadiatu

    2012-11-01

    Full Text Available Abstract Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2′-deoxyuridine (EdU to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5 and keratin 14 (K14 for basal cells, Clara cell secretory protein (CCSP for Clara cells, and acetylated tubulin (AcTub for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratified epithelium. Results Epithelial repair was fastest and most extensive in proximal trachea compared with middle and distal trachea. In unexposed mice, cell proliferation was minimal, all basal cells expressed K5, and K14-expressing basal cells were absent from most sections. Chlorine exposure resulted in the sloughing of Clara and ciliated cells from the tracheal epithelium. Two to four days after chlorine exposure, cell proliferation occurred in K5- and K14-expressing basal cells, and the number of K14 cells was dramatically increased. In the period of peak cell proliferation, few if any ciliated or Clara cells were detected in repairing trachea. Expression of ciliated and Clara cell markers was detected at later times (days 7–10, but cell proliferation was not detected in areas in which these differentiated markers were re-expressed. Fibrotic lesions were observed at days 7–10 primarily in distal trachea. Conclusion

  4. Activation of the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway in human cholesteatoma epithelium.

    Science.gov (United States)

    Liu, Wei; Yin, Tuanfang; Ren, Jihao; Li, Lihua; Xiao, Zian; Chen, Xing; Xie, Dinghua

    2014-02-01

    Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.

  5. Availability and Utilization of Pigments from Microalgae.

    Science.gov (United States)

    Begum, Hasina; Yusoff, Fatimah Md; Banerjee, Sanjoy; Khatoon, Helena; Shariff, Mohamed

    2016-10-02

    Microalgae are the major photosynthesizers on earth and produce important pigments that include chlorophyll a, b and c, β-carotene, astaxanthin, xanthophylls, and phycobiliproteins. Presently, synthetic colorants are used in food, cosmetic, nutraceutical, and pharmaceutical industries. However, due to problems associated with the harmful effects of synthetic colorants, exploitation of microalgal pigments as a source of natural colors becomes an attractive option. There are various factors such as nutrient availability, salinity, pH, temperature, light wavelength, and light intensity that affect pigment production in microalgae. This paper reviews the availability and characteristics of microalgal pigments, factors affecting pigment production, and the application of pigments produced from microalgae. The potential of microalgal pigments as a source of natural colors is enormous as an alternative to synthetic coloring agents, which has limited applications due to regulatory practice for health reasons.

  6. Skin pigmentation kinetics after UVB exposure

    DEFF Research Database (Denmark)

    Ravnbak, M.H.; Philipsen, P.A.; Wiegell, S.R.

    2008-01-01

    There have been few previous studies of the kinetics of pigmentation following ultraviolet B (UVB) exposure, and these have included only fair-skinned persons. The current study investigated pigmentation increase to steady state and fading in 12 Scandinavians and 12 Indians/Pakistanis. Over...... a period of 3 weeks the subjects were UV-irradiated 6 times on the right side of the back and 12 times on the left side using a Solar Simulator and narrowband UVB with equal sub-Minimal Melanogenesis Doses (individually predetermined). Pigmentation was measured from skin remittance at 555 urn and 660 nm...... (allowing correction for erythema). The absolute pigmentation increase was independent of pre-exposure pigmentation, therefore the percentage pigmentation increase was higher in fair-skinned volunteers. The UV dose to minimal pigmentation was higher in darker-skinned persons for single and multiple UV...

  7. Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer.

    Science.gov (United States)

    Shaykhiev, Renat; Sackrowitz, Rachel; Fukui, Tomoya; Zuo, Wu-Lin; Chao, Ion Wa; Strulovici-Barel, Yael; Downey, Robert J; Crystal, Ronald G

    2013-09-01

    CXCL14, a recently described epithelial cytokine, plays putative multiple roles in inflammation and carcinogenesis. In the context that chronic obstructive pulmonary disease (COPD) and lung cancer are both smoking-related disorders associated with airway epithelial disorder and inflammation, we hypothesized that the airway epithelium responds to cigarette smoking with altered CXCL14 gene expression, contributing to the disease-relevant phenotype. Using genome-wide microarrays with subsequent immunohistochemical analysis, the data demonstrate that the expression of CXCL14 is up-regulated in the airway epithelium of healthy smokers and further increased in COPD smokers, especially within hyperplastic/metaplastic lesions, in association with multiple genes relevant to epithelial structural integrity and cancer. In vitro experiments revealed that the expression of CXCL14 is induced in the differentiated airway epithelium by cigarette smoke extract, and that epidermal growth factor mediates CXCL14 up-regulation in the airway epithelium through its effects on the basal stem/progenitor cell population. Analyses of two independent lung cancer cohorts revealed a dramatic up-regulation of CXCL14 expression in adenocarcinoma and squamous-cell carcinoma. High expression of the COPD-associated CXCL14-correlating cluster of genes was linked in lung adenocarcinoma with poor survival. These data suggest that the smoking-induced expression of CXCL14 in the airway epithelium represents a novel potential molecular link between smoking-associated airway epithelial injury, COPD, and lung cancer.

  8. Pigment dispersion syndrome associated with intraocular lens implantation: a new surgical technique

    Science.gov (United States)

    Jordana, M Isabel Canut; Formigó, Daniel Pérez; González, Rodrigo Abreu; Reus, Jeroni Nadal

    2010-01-01

    Aims We report the case of a myopic patient who, after intraocular lens transplant in the posterior chamber, suffered elevated intraocular pressure due to pigment dispersion, with recurrent episodes of blurred vision. The patient was treated with a new surgical technique that can avoid potential iridolenticular contact. Methods Complete ophthalmologic examination and optical coherence tomography (OCT) of the anterior segment were performed. Results Contact between the pigmentary epithelium and the iris with an intraocular lens was revealed by utrasound biomicroscopy and OCT. In this case, Nd:YAG laser iridotomy and laser iridoplasty were not effective for iridolenticular separation and control of the pigment dispersion. We propose a new technique: stitches on the surface of the iris to obtain good iridolenticular separation and good intraocular pressure control. Conclusion Stitches on the iris surface should be considered as optional therapy in pigmentary glaucoma secondary to intraocular lens implantation. This surgical technique can avoid potential iridolenticular contacts more definitively. PMID:21151331

  9. Holographic films from carotenoid pigments

    Science.gov (United States)

    Toxqui-López, S.; Lecona-Sánchez, J. F.; Santacruz-Vázquez, C.; Olivares-Pérez, A.; Fuentes-Tapia, I.

    2014-02-01

    Carotenoids pigments presents in pineapple can be more than just natural dyes, which is one of the applications that now at day gives the chemical industry. In this research shown that can be used in implementing of holographic recording Films. Therefore we describe the technique how to obtain this kind of pigments trough spay drying of natural pineapple juice, which are then dissolved with water in a proportion of 0.1g to 1mL. The obtained sample is poured into glass substrates using the gravity method, after a drying of 24 hours in laboratory normal conditions the films are ready. The films are characterized by recording transmission holographic gratings (LSR 445 NL 445 nm) and measuring the diffraction efficiency holographic parameter. This recording material has good diffraction efficiency and environmental stability.

  10. Adult multifocal pigmented villonodular synovitis--clinical review.

    Science.gov (United States)

    Botez, Paul; Sirbu, Paul Dan; Grierosu, Carmen; Mihailescu, Dan; Savin, Liliana; Scarlat, Marius M

    2013-04-01

    Pigmented villonodular synovitis (PVNS) is a rare, benign proliferative disease of the synovial tissue that affects a single joint or a tendon sheath. Data from the literature present only a few cases of multifocal PVNS. This paper presents multifocal PVNS in the adult. This disease can affect bilateral shoulders, hips and knees. The diagnosis may be delayed by the slow evolution of the disease (up to ten years); some patients may be seen with late-stage degenerative joints, serious complications, painful and functionally uncompensated, with significant locomotion deficit. PVNS requires a radical treatment with prosthetic arthroplasty associated with synovectomy. Complex imaging (X-Rays, magnetic resonance imaging (MRI), ultrasound) and macroscopic appearance of the lesions during surgery confirms the clinical diagnosis of multifocal PVNS with secondary bone lesions. Histology marks the final diagnosis of multifocal PVNS. The postoperative results are good, with recovery in functional parameters of the joints with endoprosthesis.

  11. Pigmented villonodular synovitis of the temporomandibular joint: CT imaging findings.

    Science.gov (United States)

    Le, Wei-Jie; Li, Ming-Hua; Yu, Qiang; Shi, Hui-Min

    2014-01-01

    The purpose of this study was to determine the characteristic computed tomography (CT) findings of pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ). Eight subjects with PVNS were examined with both pre and post contrast CT scans. All lesions were histopathologically confirmed through surgery. CT appearances of the lesions were reviewed. Among the eight subjects, 8 (100%) demonstrated soft tissue mass and enhancement after contrast administration, 6 (75%) appeared as all or focal areas of noncontrast hyperdensity, 6 (75%) had widening of the joint spaces. Bony erosion of the mandibular condyles and articular surfaces were found in 7 (87.5%) and 6 (75%) subjects, respectively. Based on the CT findings, PVNS of the TMJ is characterized by hyperdensity soft tissue mass and further increase in density after contrast administration, bony destruction of the mandibular condyles and skull base, and intracranial extension. © 2014.

  12. Pigmented villonodular synovitis: MRI characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, T.H. [Dept. of Radiology, Univ. of California, San Diego, CA (United States)]|[Veterans Administration Medical Center, San Diego, CA (United States); Sartoris, D.J. [Dept. of Radiology, Univ. of California, San Diego, CA (United States)]|[Veterans Administration Medical Center, San Diego, CA (United States); Schweitzer, M.E. [Dept. of Radiology, Thomas Jefferson Univ. Hospital, Philadelphia, PA (United States); Resnick, D.L. [Dept. of Radiology, Univ. of California, San Diego, CA (United States)]|[Veterans Administration Medical Center, San Diego, CA (United States)

    1995-01-01

    The magnetic resonance imaging (MRI) scans of 26 patients with histopathologically proven pigmented villonodular synovitis (PVNS), involving joints but excluding tendon sheaths, were reviewed retrospectively. The purpose of this study is to define the spectrum and frequency of MRI characteristics for PVNS using conventional spin echo (in two cases before and after intravenous administration of gadopentate dimeglumine) and also gradient echo techniques. A cystic variety is presented, the MRI appearances of which have not been found in a review of the literature. (orig.)

  13. Nanoscience of an ancient pigment.

    Science.gov (United States)

    Johnson-McDaniel, Darrah; Barrett, Christopher A; Sharafi, Asma; Salguero, Tina T

    2013-02-06

    We describe monolayer nanosheets of calcium copper tetrasilicate, CaCuSi(4)O(10), which have strong near-IR luminescence and are amenable to solution processing methods. The facile exfoliation of bulk CaCuSi(4)O(10) into nanosheets is especially surprising in view of the long history of this material as the colored component of Egyptian blue, a well-known pigment from ancient times.

  14. Unusual cases of pigmented villonodular synovitis after arthroplasty.

    Science.gov (United States)

    Ma, Xiao-Mei; Xia, Chun-Yan; Fu, Pei-Liang; Liu, Hui-Min; Yu, Hong-Yu; He, Jin

    2014-01-01

    Pigmented Villonodular Synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints. The etiology is varied and unclear. We had report a 79-year-old woman had PVNS after 14 years right hip arthroplasty with metal prosthesis. Here we report another 4 patients had PVNS after arthroplasty. The second one had PVNS in the 2(th) year after hip arthroplasty with bone cement prosthesis. The specimen was brown and like usual PVNS in tissue. The third case had PVNS in the 8(th) after arthroplasty with human bone prosthesis because of the recurrence of PVNS. The proliferated synovium became black from brown. There was brown and many groups black pigment in the tissue. The fourth one had PVNS in the 4(th) year after knee arthroplasty with polyethylene prosthesis. The specimen was yellow. There was no pigment in the tissue but multinucleated giant cells with unstained foreign body. The fifth patient had PVNS in the 10(th) month after the left hip arthroplasty with metal prosthesis. The macroscopy was yellow. There were hemosiderin particles in the tissue but black metal particles. This indicates that arthroplasty with prosthesis could cause some new disease or PVNS had new etiology with different pathological show.

  15. Melanoma diagnosed in lesions previously treated by laser therapy.

    Science.gov (United States)

    Delker, Sarah; Livingstone, Elisabeth; Schimming, Tobias; Schadendorf, Dirk; Griewank, Klaus G

    2017-01-01

    Laser therapy has become a routine procedure in dermatological practice and is frequently also used for pigmented lesions. Few reports exist of melanomas diagnosed in lesions previously treated by laser therapy. Between 2007 and 2014, we identified 11 patients who presented to our department with a melanoma diagnosed in a region previously treated by laser therapy. The course of events until the diagnosis of melanoma was assessed as well as patient outcome including treatment for disease progression. No histological assessment had been performed prior to laser therapy in nine of 11 (82%) cases. Benign melanocytic lesions had been diagnosed by biopsy prior to laser therapy in the other two cases. Time from laser therapy to diagnosis of melanoma ranged from less than 1 to 10 years. Stage of disease at diagnosis varied from stage IA to IIIC. Four patients progressed to stage IV disease, of whom at least one died of melanoma. We conclude that laser treatment of pigmented lesions can complicate the diagnosis of melanoma and lead to diagnosis delay with potentially fatal consequences. Considering this risk, we believe laser therapy for pigmented lesions should either be avoided entirely or at a minimum performed only after prior histological assessment. © 2016 Japanese Dermatological Association.

  16. Diverticular bile duct lesion in chronic active hepatitis

    DEFF Research Database (Denmark)

    Vyberg, M

    1989-01-01

    Liver needle biopsies from patients with non-A, non-B chronic active hepatitis and so-called abnormal bile duct epithelium were studied with a three-dimensional method. Photographs of bile duct structures in serial sections were transferred to acrylic plates. Five bile duct lesions of a not previ......Liver needle biopsies from patients with non-A, non-B chronic active hepatitis and so-called abnormal bile duct epithelium were studied with a three-dimensional method. Photographs of bile duct structures in serial sections were transferred to acrylic plates. Five bile duct lesions...... cells, but most were larger, with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, sometimes with periodic acid-Schiff-positive, diastase-resistant granules. The lesions were only partly surrounded by a basement membrane. They were all embedded in a tight mononuclear inflammatory...... infiltrate associated with pronounced periportal piecemeal necrosis. In two cases, a germinal center was adjacent to the epithelium. The pathogenesis of the diverticular bile duct lesion is unknown, but the diverticuli probably represent Hering ducts and groups of periportal liver cells which have escaped...

  17. Dermoscopic findings and histological correlation of the acral volar pigmented maculae in Laugier-Hunziker syndrome.

    Science.gov (United States)

    Sendagorta, Elena; Feito, Marta; Ramírez, Paloma; Gonzalez-Beato, María; Saida, Toshiaki; Pizarro, Angel

    2010-11-01

    Laugier-Hunziker syndrome (LHS) is an acquired, benign, macular hyperpigmentation of the lips and oral mucosa, often associated with pigmentation of the nails. Volar acral maculae on the palms and fingertips of patients affected by LHS are a typical feature of this rare entity. Dermoscopic examination of these maculae has been described in a previous report, in which authors found a parallel-furrow pattern. We describe two cases in which a parallel-ridge pattern (PRP) was found on the dermoscopic examination of the pigmented acral lesions. Histological examination showed increased melanin in basal keratinocytes, which was most prominent in those located at the crista intermedia profunda, that is, in the epidermal rete ridges underlying the surface ridges. In our study, dermoscopic features of the pigmented maculae found on LHS differed from those previously described. In addition, by means of this case report, the histological features of these lesions are described for the first time, showing an excellent correlation with dermoscopy. The reported cases prove that although the PRP is very specific of melanoma, it is also possible to find it in benign lesions. Therefore, we must be familiar with the differential diagnosis of PRP, and take into consideration the clinical context in which we find it. Further studies are needed to increase our knowledge on the histological and dermoscopic features of acral pigmented maculae of LHS.

  18. Morphological evaluation of normal human corneal epithelium

    DEFF Research Database (Denmark)

    Ehlers, Niels; Heegaard, Steffen; Hjortdal, Jesper

    2010-01-01

    PURPOSE: The human corneal epithelium is usually described as a 50-µm-thick layer of regular stratified squamous non-keratinized cells with a thickness of 5-7 cells. The purpose of this study is systemically to revisit the histopathological appearance of 100 corneas. METHODS: 5-µm-thick sections...... in Bowman's membrane. No intraepithelial microcysts, as found in Meesmann corneal dystrophy, were observed. CONCLUSION: The total corneal thickness was higher than reported in in vivo studies and with a wider variation. This may be an effect of uncontrolled swelling and dehydration during preparation...

  19. Pigmented Villonodular Synovitis Causing Osteonecrosis of the Femoral Head: A Case Report

    Directory of Open Access Journals (Sweden)

    Tomohiro Mimura

    2013-01-01

    Full Text Available We report a case of a 27-year-old man with pigmented villonodular synovitis of the hip joint with coincident osteonecrosis of the femoral head. According to our review of the English-language literature, no detailed report of osteonecrosis of the femoral head complicated with pigmented villonodular synovitis has been published. Preoperative X-ray images showed joint narrowing and severe multiple bone erosions at the acetabulum and femoral neck. Magnetic resonance imaging revealed a low-intensity band attributable to osteonecrosis of the femoral head and massive diffuse pigmented villonodular synovitis lesions. Comparison of a three-dimensional computed tomographic image of this patient with an angiographic image of a normal individual demonstrated proximity of the pigmented villonodular synovitis-induced bone erosions to the medial and lateral femoral circumflex arteries and retinacular arteries, suggesting likely the compromise of the latter by the former. We propose that the massive pigmented villonodular synovitis may have contributed to the pathogenesis of osteonecrosis of the femoral head in this patient. We performed open synovectomy and total hip arthroplasty. No operative complications occurred, and no recurrence of the pigmented villonodular synovitis was detected for 3 years after the operation.

  20. Localized form of pigmented villonodular synovitis of the knee: the meniscal mime.

    Science.gov (United States)

    Bouguennec, N; Meyer, A; Graveleau, N

    2014-04-01

    The localized form of pigmented villonodular synovitis of the knee is a rare condition with non-specific symptoms. This makes diagnosis especially difficult when the meniscus is affected. A full assessment with several imaging modalities can help support the preoperative diagnosis. But in the case reported here, the full clinical and paraclinical assessment (X-rays, CT arthrography and MRI) was wrong--the localized form of pigmented villonodular synovitis had mimicked a lateral meniscus injury and was only detected during arthroscopy. The lesion was excised surgically and the diagnosis was confirmed through postoperative histopathology.

  1. Picobiophotonics for the investigation of pigment-pigment and pigment-protein interactions in photosynthetic complexes

    OpenAIRE

    Schmitt, Franz-Josef

    2011-01-01

    Anregungsenergietransfer-(EET)-prozesse wurden in verschiedenen photosynthetischen Pigment-Protein-Komplexen mit zeit- und wellenlängenkorrelierter Einzelphotonenspektroskopie (TWCSPC) analysiert. Ein neuer mobiler 16-Kanal Photomultiplier mit flexibler Faseroptik, austauschbaren Lichtquellen und einem Kryostaten (10 K – 350 K) wurde für die Spektroskopie von Proben in Küvetten, auf Oberflächen oder von ganzen Blättern in vivo aufgebaut. Das System stellt einen mobilen Messplatz auf Grundlage...

  2. STRUCTURAL PARTICULARITIES OF THE EPITHELIUM LINING THE LAMB EPIGLOTTIS

    Directory of Open Access Journals (Sweden)

    Vasile Rus

    2016-11-01

    Full Text Available Epiglottis presents a central axis covered by mucosa. The aim of this study was highlighting the type of epithelium lining the lamb epiglottis. Thus, we histologically processed the epiglottis from 3 lambs. The epithelium lining the whole epiglottis surface is non-keratinized stratified squamous, with different thickness from one side to the other. Hence, on the pharyngeal side the epithelium is twice as thick as the one found on the laryngeal side.

  3. EFFECT OF FUNDUS PIGMENT ON RESPONSE OF RABBIT RETINA TO TRANSPUPILLARY THERMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the effect of fundus pigment on the response of the retina to transpupillary thermotherapy (TTT). Methods The retina were irradiated with 810 nm diode laser in 16 eyes of 8 pigmented rabbits and 12 eyes of 6 albino rabbits. The spot size was 1.2 mm; the duration was 60 s; and powers were 50, 80, 150 and 300 mW for pigmented rabbits and 800, 1 200 and 1 500mW for albino rabbits. All of the eyes were followed up with ophthalmolscope. The fundus was photographed and examined histologically with optic microscope immediately and 1 month after TTT respectively. Results The changes of the fundus and the histological examination were not significant immediately and 1 month after TTT in 50 mW group of pigmented rabbit and 800 mW of albino rabbit. Grey spot on the retina was observed on the fundus in 80 mW group of pigmented rabbit and 1 200 mW of albino rabbit immediately after TTT. The structure of the retina remained intact and subretinal fluid was observed histologically. Grey spot was still visible on the fundus, though the fluid was absorbed after 1 month. As the power of diode laser was increased to 150 mW for pigmented rabbits and 1500 mW for albino rabbit, fundus white spots were observed and the outer retina was destroyed while photoreceptors existed immediately after TTT. Pigmentation was found in white lesions and the fibrous proliferation was found in choroid 1 month after TTT. Prominent white spot was seen on the fundus immediately after laser irradiation of 300 mW in pigmented rabbits and the structure of the retina was obscured. One month after TTT, dense pigmentation appeared at laser lesions. The retina was thinner. There was prominent fibrous proliferation in the choroid. Conclusion The fundus pigment seems to play an important role in the response of the retina to TTT. The reaction of the retina is in proportion to the intensity of laser.

  4. Acid phosphatase and lipid peroxidation in human cataractous lens epithelium

    Directory of Open Access Journals (Sweden)

    Vasavada Abhay

    1993-01-01

    Full Text Available The anterior lens epithelial cells undergo a variety of degenerative and proliferative changes during cataract formation. Acid phosphatase is primarily responsible for tissue regeneration and tissue repair. The lipid hydroperoxides that are obtained by lipid peroxidation of polysaturated or unsaturated fatty acids bring about deterioration of biological membranes at cellular and tissue levels. Acid phosphatase and lipid peroxidation activities were studied on the lens epithelial cells of nuclear cataract, posterior subcapsular cataract, mature cataract, and mixed cataract. Of these, mature cataractous lens epithelium showed maximum activity for acid phosphatase (516.83 moles of p-nitrophenol released/g lens epithelium and maximum levels of lipid peroxidation (86.29 O.D./min/g lens epithelium. In contrast, mixed cataractous lens epithelium showed minimum activity of acid phosphatase (222.61 moles of p-nitrophenol released/g lens epithelium and minimum levels of lipid peroxidation (54.23 O.D./min/g lens epithelium. From our study, we correlated the maximum activity of acid phosphatase in mature cataractous lens epithelium with the increased areas of superimposed cells associated with the formation of mature cataract. Likewise, the maximum levels of lipid peroxidation in mature cataractous lens epithelium was correlated with increased permeability of the plasma membrane. Conversely, the minimum levels of lipid peroxidation in mixed cataractous lens epithelium makes us presume that factors other than lipid peroxidation may also account for the formation of mixed type of cataract.

  5. Collagenase-3 expression in periapical lesions: an immunohistochemical study.

    Science.gov (United States)

    Bhalla, G; Astekar, M S; Ramesh, G; Kaur, P; Sowmya, G V

    2014-08-01

    Collagenase-3 (matrix metalloproteinase-13) is a metalloproteinase (MMP) that is associated with bone lesions and exhibits variable expression patterns in odontogenic cysts; it may play a role in regulating focal proliferation and maturation of jaw cyst epithelium. We studied the localization, staining intensity and distribution of collagenase-3 in 13 periapical granulomas with epithelium, 16 periapical granulomas without epithelium and 10 radicular cysts using archived formalin fixed, paraffin embedded tissues. A monoclonal antibody against human collagenase-3 was used to evaluate its expression. Immunohistochemical staining intensities of collagenase-3 in all periapical lesions were (-), 4 (10%); (+), 1 (3%); (++), 22 (56%) and (+++), 12 (31%); differences were not statistically significant. Immunohistochemical distribution of collagenase-3 in epithelial cells was (-), 17 (44%); (+), 17 (44%); (++), 5 (13%); in fibroblasts it was (-), 8 (20%); (+), 23 (59%); (++), 8 (21%); in plasma cells it was (-), 7 (18%); (+), 22 (56%); (++), 10 (26%); in macrophages it was (-), 7 (18%); (+), and 15 (38%); and (++), 17 (44%). Statistically significant differences were found in epithelial cells (p = 0.00) and fibroblasts (p = 0.02), whereas differences were not statistically significant for plasma cells and macrophages. Collagenase-3 may play a role in the conversion of a periapical granuloma with epithelium to radicular cyst. MMP's influence not only epithelial rest cell migration, but also invasion of various stromal cells into granulomatous tissue.

  6. Natural food pigments application in food products

    Directory of Open Access Journals (Sweden)

    Emilia Janiszewska-Turak

    2016-12-01

    Full Text Available Natural pigments, food compounds, are responsible for the colour of the products. These additives can impart, to deepen or renew the colour of the product, if it has been lost while processing. They also improve the taste of the product and facilitate its identification. It is hard to imagine today’s food industry without the use of pigments. Presently, more and more conscious con­sumers are demanding products to be coloured with natural pigments or any pigment added to the final product. Artificial pigments are considered to be harmful and undesirable so food manufacturers focus on the use of natural colour substances. 16 natural pigments are presently permitted to be used. These compounds are: betalains – betanin, quinones – cochineal, flavonoids – anthocyan­ins, isoprenoids – carotene, annatto (bixin, norbixin, paprika extract, lutein, canthaxanthin, porphyrins – chlorophylls and chlorophyllins and copper complexes of these compounds, and others: caramels, curcumin, or plant coal.

  7. Pigment reduction in nevus of Ota following leech therapy

    Science.gov (United States)

    Rastogi, Sanjeev; Chaudhari, Priyanka

    2014-01-01

    Nevus of Ota is a congenital blue-gray color nevus afflicting unilaterally, the area near the eyes. It poses a huge cosmetic concern besides being a potential threat for developing melanoma sometime in the course of the disease. The treatment options are neither many nor promising besides they are too expensive. We have treated a case of nevus of Ota with leech therapy where leech was applied upon the lesion for five times spanned in a period of 2 months. The results in terms of change in the color of lesion were evaluated with the help of serial photographs following every treatment session to mark the level of color changes in the lesion. A substantial reduction in color of the nevus was reported following the completion of the therapy. The results were demonstrated with the photographs. Although, recommended as the classical Ayurvedic management for skin diseases, leech therapy is not reported earlier in such conditions. It proposes a novel approach to deal with such congenital pigment lesions where other options are not promising. PMID:24948864

  8. Pigment reduction in nevus of Ota following leech therapy

    Directory of Open Access Journals (Sweden)

    Sanjeev Rastogi

    2014-01-01

    Full Text Available Nevus of Ota is a congenital blue-gray color nevus afflicting unilaterally, the area near the eyes. It poses a huge cosmetic concern besides being a potential threat for developing melanoma sometime in the course of the disease. The treatment options are neither many nor promising besides they are too expensive. We have treated a case of nevus of Ota with leech therapy where leech was applied upon the lesion for five times spanned in a period of 2 months. The results in terms of change in the color of lesion were evaluated with the help of serial photographs following every treatment session to mark the level of color changes in the lesion. A substantial reduction in color of the nevus was reported following the completion of the therapy. The results were demonstrated with the photographs. Although, recommended as the classical Ayurvedic management for skin diseases, leech therapy is not reported earlier in such conditions. It proposes a novel approach to deal with such congenital pigment lesions where other options are not promising.

  9. Pigment reduction in nevus of Ota following leech therapy.

    Science.gov (United States)

    Rastogi, Sanjeev; Chaudhari, Priyanka

    2014-04-01

    Nevus of Ota is a congenital blue-gray color nevus afflicting unilaterally, the area near the eyes. It poses a huge cosmetic concern besides being a potential threat for developing melanoma sometime in the course of the disease. The treatment options are neither many nor promising besides they are too expensive. We have treated a case of nevus of Ota with leech therapy where leech was applied upon the lesion for five times spanned in a period of 2 months. The results in terms of change in the color of lesion were evaluated with the help of serial photographs following every treatment session to mark the level of color changes in the lesion. A substantial reduction in color of the nevus was reported following the completion of the therapy. The results were demonstrated with the photographs. Although, recommended as the classical Ayurvedic management for skin diseases, leech therapy is not reported earlier in such conditions. It proposes a novel approach to deal with such congenital pigment lesions where other options are not promising.

  10. Argon Laser Photoablation for Postburn Conjunctival Pigmentation

    Directory of Open Access Journals (Sweden)

    Seong Joon Ahn

    2014-01-01

    Full Text Available We report a case of an ocular burn injury from boiling water which resulted in conjunctival pigmentation, 1 week following injury. For cosmetic purposes, 2 sessions of argon laser photoablation were performed. One month after laser treatment, conjunctival pigmentation had been successfully removed and the patient was very satisfied with the results. Argon laser photoablation may be an effective way to remove postburn conjunctival pigmentation.

  11. PRODUCTION OF MONASCUS-LIKE AZAPHILONE PIGMENT

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to the field of biotechnological production of polyketide based colorants from filamentous fungi, in particular a method for preparing a biomass comprising a Monascus-like pigment composition from a nontoxigenic and non-pathogenic fungal source. The present invention...... further relates to use of the Monascus-like pigment composition as a colouring agent for food items and/or non-food items, and a cosmetic composition comprising the Monascus-like pigment composition....

  12. Non-photosynthetic pigments as potential biosignatures

    Science.gov (United States)

    Schwieterman, E. W.; Cockell, C. S.; Meadows, V. S.

    2014-03-01

    Photosynthetic organisms on Earth produce potentially detectable surface reflectance biosignatures due in part to the spectral location and strength of pigment absorption. However, life on Earth uses pigments for a multitude of purposes other than photosynthesis, including coping with extreme environments. Macroscopic environments exist on Earth where the surface reflectance is significantly altered by a nonphotosynthetic pigment, such as the case of hypersaline lakes and ponds (Oren et al. 1992). Here we explore the nature and potential detectability of non-photosynthetic pigments in disk-averaged planetary observations using a combination of laboratory measurements and archival reflectance spectra, along with simulated broadband photometry and spectra. The in vivo visible reflectance spectra of a cross section of pigmented microorganisms are presented to illustrate the spectral diversity of biologically produced pigments. Synthetic broadband colors are generated to show a significant spread in color space. A 1D radiative transfer model (Meadows & Crisp 1996; Crisp 1997) is used to approximate the spectra of scenarios where pigmented organisms are widespread on planets with Earth-like atmospheres. Broadband colors are revisited to show that colors due to surface reflectivity are not robust to the addition of scattering and absorption effects from the atmosphere. We consider a èbest case' plausible scenario for the detection of nonphotosynthetic pigments by using the Virtual Planetary Laboratory's 3D spectral Earth model (Robinson et al. 2011) to explore the detectability of the surface biosignature produced by pigmented halophiles that are widespread on an Earth-analog planet.

  13. Evaluation of the progression rate of atrophy lesions in punctate inner choroidopathy (PIC) based on autofluorescence analysis.

    Science.gov (United States)

    Hua, Rui; Liu, Limin; Chen, Lei

    2014-12-01

    To investigate the autofluorescence (AF) characteristics of punctate inner choroidopathy (PIC) and to evaluate the progression rate of retinal pigment epithelium (RPE) atrophy lesions in PIC using confocal scanning laser ophthalmoscopy. Twenty-two eyes of 14 PIC cases and 21 eyes of 21 non-proliferative diabetic retinopathy (NPDR) cases which received retinal coagulation as a control group were enrolled in this study. Enhanced depth imaging optical coherence tomography (EDI-OCT) and AF were recorded from all patients at 18 months follow-up. The RPE atrophy areas of PIC and laser scars in NPDR were analyzed using the Region Finder software of the Heidelberg Eye Explorer. This software allows direct export of AF images from the database and semi-automated detection of atrophic areas by shadow correction, vessel detection, and selection of seed points. At baseline, both hyperfluorescence and hypofluorescence were observed in the lesions of PIC eyes with a focal elevation of RPE and corresponding disruption of the ellipsoid region of the inner segment ellipsoid zone (EZ). In contrast, hypo-AF was detected when there was a lack of RPE. The mean progression rate of RPE atrophy in PIC and NPDR were 3.735 mm(2)/year (0.056-0.545) and 0.127 mm(2)/year (0.015-0.466), respectively. Compared with the atrophy area in the last visit, the progression rate in PIC was significantly greater than that in NPDR (Z=5.615, P<0.0001). The results of AF reflect the status of PIC and the progression rate of RPE atrophy in PIC, which can be used to predict the progress of PIC noninvasively. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Ultraviolet pigments in birds evolved from violet pigments by a single amino acid change

    OpenAIRE

    Yokoyama, Shozo; Radlwimmer, F. Bernhard; Blow, Nathan S.

    2000-01-01

    UV vision has profound effects on the evolution of organisms by affecting such behaviors as mating preference and foraging strategies. Despite its importance, the molecular basis of UV vision is not known. Here, we have transformed the zebra finch UV pigment into a violet pigment by incorporating one amino acid change, C84S. By incorporating the reverse mutations, we have also constructed UV pigments from the orthologous violet pigments of the pigeon and chicken. These results and comparative...

  15. Histopathological observations of human periimplantitis lesions.

    Science.gov (United States)

    Berglundh, Tord; Gislason, Orn; Lekholm, Ulf; Sennerby, Lars; Lindhe, Jan

    2004-05-01

    The aim of the present study was to analyze some characteristics of advanced and progressive periimplantitis lesions in man. Soft tissue biopsies were obtained from 12 implants in six patients. The implants had been in function between 4 and 21 years and were, with one exception, located in the maxilla. The radiographic examination performed prior to biopsy revealed that all sites exhibited advanced bone loss. Further, clinical signs of severe inflammation, such as suppuration, swelling and/or fistula formation were detected in the majority of sites and seven of the 12 implants were found to be mobile at biopsy. Each biopsy was following fixation embedded in epoxy resin and sections were prepared for histometric and morphometric analysis. It was demonstrated (i). that all soft tissue units harbored large inflammatory cell infiltrates (ICT) that extended to a position apical of a pocket epithelium and (ii). that about 60% of the lesions were occupied by inflammatory cells, among which plasma cells dominated. Numerous amounts of PMN cells occurred not only in the pocket epithelium and adjacent connective tissue areas, but were also present in peri-vascular compartments in more central areas of the ICT.

  16. Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters.

    Science.gov (United States)

    Keenan, C M; Kelly, D P; Bogdanffy, M S

    1990-08-01

    Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE.

  17. [Pigmentation abnormalities in the course of topical immunotherapy of alopecia areata].

    Science.gov (United States)

    Valsecchi, R; Pansera, B; Rossi, A; Cainelli, T

    1989-01-01

    Pigmentation troubles have been associated in the past years with contact dermatitis and patch-testing. Contact allergy and increase of pigmentation has been associated with Tinopal; on the other hand contact allergy and depigmentation have been associated with many substances such as DNCB, squaric acid dibutylester (SADBE), carbyne, alstroemeria. Leukoderma can also be produced by irritant compound such as phenols, catechols and mercaptoamines. During 1978 and 1984 we have treated 132 patients suffering from alopecia areata with DNCB or SADBE: 51 patients have been treated by DNCB and 81 by SADBE. During the treatment 10 patients developed a leukoderma vitiligo-like localized to the areas of topical application of the allergens and to the flare-up site; one patient had an increase of pigmentation. Lesions vitiligo-like appeared 10-15 weeks after the onset of treatment. Among the patients who developed leukoderma, 4 had a personal history of vitiligo. The possible pathogenetic mechanisms are discussed.

  18. Radiation response of the mouse tongue epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Moses, R.; Kummermehr, J.

    1986-01-01

    Mouse tongue mucosa has been used as a model to study dose responses to local irradiation. Although the irradiation procedures is less feasible and more time-consuming than e.g. snout irradiation, the tongue is the only location where a reasonable area of intraoral, multilayered epithelium in the mouse can be locally treated and scored, and a relatively small burden is imposed on the animal. In pilot experiments with external 300 kV x-irradiation just tolerated by the lip, the authors did not see critical damage to the tongue. In the present model, the onset of denudation was not correctly predicted by the normal turnover time of the tissue.

  19. Global expression profiling of globose basal cells and neurogenic progression within the olfactory epithelium.

    Science.gov (United States)

    Krolewski, Richard C; Packard, Adam; Schwob, James E

    2013-03-01

    Ongoing, lifelong neurogenesis maintains the neuronal population of the olfactory epithelium in the face of piecemeal neuronal turnover and restores it following wholesale loss. The molecular phenotypes corresponding to different stages along the progression from multipotent globose basal cell (GBC) progenitor to differentiated olfactory sensory neuron are poorly characterized. We used the transgenic expression of enhanced green fluorescent protein (eGFP) and cell surface markers to FACS-isolate ΔSox2-eGFP(+) GBCs, Neurog1-eGFP(+) GBCs and immature neurons, and ΔOMP-eGFP(+) mature neurons from normal adult mice. In addition, the latter two populations were also collected 3 weeks after olfactory bulb ablation, a lesion that results in persistently elevated neurogenesis. Global profiling of mRNA from the populations indicates that all stages of neurogenesis share a cohort of >2,100 genes that are upregulated compared to sustentacular cells. A further cohort of >1,200 genes are specifically upregulated in GBCs as compared to sustentacular cells and differentiated neurons. The increased rate of neurogenesis caused by olfactory bulbectomy had little effect on the transcriptional profile of the Neurog1-eGFP(+) population. In contrast, the abbreviated lifespan of ΔOMP-eGFP(+) neurons born in the absence of the bulb correlated with substantial differences in gene expression as compared to the mature neurons of the normal epithelium. Detailed examination of the specific genes upregulated in the different progenitor populations revealed that the chromatin modifying complex proteins LSD1 and coREST were expressed sequentially in upstream ΔSox2-eGFP(+) GBCs and Neurog1-eGFP(+) GBCs/immature neurons. The expression patterns of these proteins are dynamically regulated after activation of the epithelium by methyl bromide lesion.

  20. Effect of acetic acid on optical coherence tomography (OCT) images of cervical epithelium.

    Science.gov (United States)

    Gallwas, Julia; Stanchi, Anna; Dannecker, Christian; Ditsch, Nina; Mueller, Susanna; Mortensen, Uwe; Stepp, Herbert

    2014-11-01

    Optical coherence tomography (OCT) can be used as an adjunct to colposcopy in the identification of precancerous and cancerous cervical lesions. The purpose of this study was to investigate the effect of acetic acid on OCT imaging. OCT images were taken from unsuspicious and suspicious areas of fresh conization specimens immediately after resection and 3 and 10 min after application of 6 % acetic acid. A corresponding histology was obtained from all sites. The images taken 3 and 10 min after application of acetic acid were compared to the initial images with respect to changes in brightness, contrast, and scanning depth employing a standard nonparametric test of differences of proportions. Further, mean intensity backscattering curves were calculated from all OCT images in the histological groups CIN3, inflammation, or normal epithelium. Mean difference profiles within each of these groups were determined, reflecting the mean differences between the condition before application of acetic acid and the exposure times 3 and 10 min, respectively. According to the null hypothesis, the difference profiles do not differ from profiles fluctuating around zero in a stationary way, which implies that the profiles do not differ significantly from each other. The null hypothesis was tested employing the KPSS test. The visual analysis of 137 OCT images from 46 sites of 10 conization specimens revealed a statistically significant increase in brightness for all three groups and a statistically significant decrease in contrast for normal epithelium after 10 min. Further, an increase in scanning depth was noted for normal epithelium after 10 min and for CIN3 after 3 min. The analysis of mean intensity profiles showed an increased backscattering intensity after application of acetic acid. Acetic acid significantly affects the quality of OCT images. Overall brightness and scanning depth increase with the opposite effect regarding the image contrast. Whether the observed changes

  1. Effects of PDTC on the Proliferation and PCNA Expression of Human Retinal Pigment Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    HU Jun; LI Guigang

    2006-01-01

    To investigate the effects of pyrrolidine dithiocarbamate (PDTC) on the proliferation and PCNA (proliferating cell nuclear antigen) expression of cultured human retinal pigment epithelium cells, human retinal pigment epithelium cells (RPE) were cultured from normal adults who died accidentally. The effects of PDTC on the proliferation of RPE cells were examined by using methyl thiazlyl tetrazolium (MTT) assay. The effects of PDTC on the PCNA expression of RPE cells were immunohistochemically examined by employing biological image analysis system (BIAS). After treatment with PDTC of various of concentration ranging from 0.062 to 1 g/L for 24 h, or concentrations ranging from 0. 031 to 1 g/L, the proliferation of RPE cells decreased in a dose-dependent manner. After treatment with PDTC of concentration varying from 0. 062 to 1 g/L for 24 h, the PCNA expression was also suppressed in a dose-dependent manner. It is concluded that PDTC can inhibit the proliferation of RPE cells in vitro in a dose-and time-dependent manner, at least in part,by down-regulating the expression of PCNA. PDTC may be used to prevent and treat the proliferative vitreoretinopathy (PVR).

  2. Superficial Automated Keratopigmentation for Iris and Pupil Simulation Using Micronized Mineral Pigments and a New Puncturing Device: Experimental Study.

    Science.gov (United States)

    Rodriguez, Alejandra E; Amesty, Maria A; El Bahrawy, Mohammed; Rey, Severino; Alio Del Barrio, Jorge; Alio, Jorge L

    2017-09-01

    To study the outcomes and tolerance of micronized mineral pigments for corneal tattooing, using a superficial automated keratopigmentation (SAK) technique in an experimental animal model and a new puncture device to inject the pigments into the corneal stroma. Forty eyes of 40 New Zealand rabbits were included in this study. The animals were divided into groups A and B. Both groups underwent SAK using a new automated keratopigmentation device. Micronized mineral pigments were injected through the epithelium into the corneal stroma to replicate the iris color in 25 eyes (group A), and black color was used to replicate the pupil in 15 eyes (group B). Slit-lamp examination was performed to evaluate the outcome. Histopathological examination was also performed to ascertain the presence of pigment dispersion, inflammation, and/or neovascularization. All 40 eyes showed good cosmetic appearance after keratopigmentation. No intraoperative complications were detected. At the first week, mild or moderated conjunctival injection was observed in 13 eyes and transitory corneal epithelial defects were also detected in 27 eyes. Examination was unremarkable 2, 4, and 6 months after surgery. No neovascularization was detected in any case in the histopathology study. SAK using a new automated puncture device and micronized mineral pigments achieved good cosmetic outcomes for iris and pupil simulation. This method could be a valid alternative to treat serious cosmetic eye problems that affect the superficial cornea or functional problems, such as photophobia or diplopia secondary to iris defects or trauma.

  3. Spectral tuning of deep red cone pigments.

    Science.gov (United States)

    Amora, Tabitha L; Ramos, Lavoisier S; Galan, Jhenny F; Birge, Robert R

    2008-04-22

    Visual pigments are G-protein-coupled receptors that provide a critical interface between organisms and their external environment. Natural selection has generated vertebrate pigments that absorb light from the far-UV (360 nm) to the deep red (630 nm) while using a single chromophore, in either the A1 (11- cis-retinal) or A2 (11- cis-3,4-dehydroretinal) form. The fact that a single chromophore can be manipulated to have an absorption maximum across such an extended spectral region is remarkable. The mechanisms of wavelength regulation remain to be fully revealed, and one of the least well-understood mechanisms is that associated with the deep red pigments. We investigate theoretically the hypothesis that deep red cone pigments select a 6- s- trans conformation of the retinal chromophore ring geometry. This conformation is in contrast to the 6- s- cis ring geometry observed in rhodopsin and, through model chromophore studies, the vast majority of visual pigments. Nomographic spectral analysis of 294 A1 and A2 cone pigment literature absorption maxima indicates that the selection of a 6- s- trans geometry red shifts M/LWS A1 pigments by approximately 1500 cm (-1) ( approximately 50 nm) and A2 pigments by approximately 2700 cm (-1) ( approximately 100 nm). The homology models of seven cone pigments indicate that the deep red cone pigments select 6- s- trans chromophore conformations primarily via electrostatic steering. Our results reveal that the generation of a 6- s- trans conformation not only achieves a significant red shift but also provides enhanced stability of the chromophore within the deep red cone pigment binding sites.

  4. Challenges and opportunities for tissue-engineering polarized epithelium.

    Science.gov (United States)

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  5. Effect of curcumin on aging retinal pigment epithelial cells

    Directory of Open Access Journals (Sweden)

    Zhu W

    2015-09-01

    Full Text Available Wei Zhu,1,* Yan Wu,2,* Yi-Fang Meng,1 Jin-Yu Wang,1 Ming Xu,1 Jian-Jun Tao,1 Jiong Lu1 1Department of Ophthalmology, Changshu No 2 People’s Hospital, Changshu, 2Department of Ophthalmology, The First People’s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Age-related macular degeneration (AMD is now one of the leading causes of blindness in the elderly population. The antioxidative effects of curcumin on aging retinal pigment epithelial (RPE cells are still unclear. We conducted an in vitro study to investigate the effects of curcumin on aging RPE cells. A pulsed H2O2 exposure aging model was adopted. Aging RPE cells were treated with curcumin 20 µM, 40 µM, and 80 µM. Apoptosis of RPE cells was analyzed by flow cytometry. The intracellular reactive oxygen species concentration was detected using a specific probe and apoptosis-associated proteins were detected by Western blot. Expression of oxidative biomarkers, including superoxide dismutase, maleic dialdehyde, and glutathione, was detected commercially available assay kits. Compared with normal cells, lower cell viability, higher apoptosis rates, and more severe oxidation status were identified in the aging RPE cell model. Curcumin improved cell viability and decreased apoptosis and oxidative stress. Further, curcumin had a significant influence on expression of apoptosis-associated proteins and oxidative stress biomarkers. In conclusion, treatment with curcumin was able to regulate proliferation, oxidative stress, and apoptosis in aging RPE cells. Accordingly, application of curcumin may be a novel strategy to protect against age-related change in AMD. Keywords: curcumin, retinal pigment epithelium, apoptosis, age-related macular degeneration

  6. Yap and Taz regulate retinal pigment epithelial cell fate.

    Science.gov (United States)

    Miesfeld, Joel B; Gestri, Gaia; Clark, Brian S; Flinn, Michael A; Poole, Richard J; Bader, Jason R; Besharse, Joseph C; Wilson, Stephen W; Link, Brian A

    2015-09-01

    The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Tead-responsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap-dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson's chorioretinal atrophy and congenital retinal coloboma. © 2015. Published by The Company of Biologists Ltd.

  7. Lesion Border Detection in Dermoscopy Images

    CERN Document Server

    Celebi, M Emre; Schaefer, Gerald; Stoecker, William V; 10.1016/j.compmedimag.2008.11.002

    2010-01-01

    Background: Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Due to the difficulty and subjectivity of human interpretation, computerized analysis of dermoscopy images has become an important research area. One of the most important steps in dermoscopy image analysis is the automated detection of lesion borders. Methods: In this article, we present a systematic overview of the recent border detection methods in the literature paying particular attention to computational issues and evaluation aspects. Conclusion: Common problems with the existing approaches include the acquisition, size, and diagnostic distribution of the test image set, the evaluation of the results, and the inadequate description of the employed methods. Border determination by dermatologists appears to depend upon higher-level knowledge, therefore it is likely that the incorporation of domain knowledge in automated methods will enable them to perform better, especially in ...

  8. [The new era of epithelium-targeted drug development].

    Science.gov (United States)

    Shimizu, Yoshimi; Nagase, Shotaro; Yagi, Kiyohito; Kondoh, Masuo

    2014-01-01

    Epithelium plays pivotal roles in biological barrier separating the inside of body and the outside environment. Ninety percent of malignant tumors are derived from epithelium. Most pathological microorganisms invade into the body from mucosal epithelium. Thus, epithelium is potential targets for drug development. Claudins (CLs), a family of tetra-transmembrane protein consisting of over 20 members, are structural and functional components of tight junction-seals in epithelium. Modulation of CL-seals enhanced mucosal absorption of drugs. CLs are often over-expressed in malignant tumors. CL-4 expression is increased in the epithelial cells covering the mucosal immune tissues. Very recently, CLs are also expected to be targets for traumatic brain injury and regenerative therapy. In this review, we overview the past, the present and the future of CLs-targeted drug development.

  9. Ultraviolet pigments in birds evolved from violet pigments by a single amino acid change

    Science.gov (United States)

    Yokoyama, Shozo; Radlwimmer, F. Bernhard; Blow, Nathan S.

    2000-01-01

    UV vision has profound effects on the evolution of organisms by affecting such behaviors as mating preference and foraging strategies. Despite its importance, the molecular basis of UV vision is not known. Here, we have transformed the zebra finch UV pigment into a violet pigment by incorporating one amino acid change, C84S. By incorporating the reverse mutations, we have also constructed UV pigments from the orthologous violet pigments of the pigeon and chicken. These results and comparative amino acid sequence analyses of the pigments in vertebrates demonstrate that many avian species have achieved their UV vision by S84C. PMID:10861005

  10. Inactivation of Pmel alters melanosome shape but has only a subtle effect on visible pigmentation.

    Directory of Open Access Journals (Sweden)

    Anders R Hellström

    2011-09-01

    Full Text Available PMEL is an amyloidogenic protein that appears to be exclusively expressed in pigment cells and forms intralumenal fibrils within early stage melanosomes upon which eumelanins deposit in later stages. PMEL is well conserved among vertebrates, and allelic variants in several species are associated with reduced levels of eumelanin in epidermal tissues. However, in most of these cases it is not clear whether the allelic variants reflect gain-of-function or loss-of-function, and no complete PMEL loss-of-function has been reported in a mammal. Here, we have created a mouse line in which the Pmel gene has been inactivated (Pmel⁻/⁻. These mice are fully viable, fertile, and display no obvious developmental defects. Melanosomes within Pmel⁻/⁻ melanocytes are spherical in contrast to the oblong shape present in wild-type animals. This feature was documented in primary cultures of skin-derived melanocytes as well as in retinal pigment epithelium cells and in uveal melanocytes. Inactivation of Pmel has only a mild effect on the coat color phenotype in four different genetic backgrounds, with the clearest effect in mice also carrying the brown/Tyrp1 mutation. This phenotype, which is similar to that observed with the spontaneous silver mutation in mice, strongly suggests that other previously described alleles in vertebrates with more striking effects on pigmentation are dominant-negative mutations. Despite a mild effect on visible pigmentation, inactivation of Pmel led to a substantial reduction in eumelanin content in hair, which demonstrates that PMEL has a critical role for maintaining efficient epidermal pigmentation.

  11. Thin Layer Chromatography (TLC) of Chlorophyll Pigments.

    Science.gov (United States)

    Foote, Jerry

    1984-01-01

    Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)

  12. Nanoscale porosity in pigments for chemical sensing

    OpenAIRE

    Kemling, Jonathan W.; Suslick, Kenneth S.

    2011-01-01

    Porous pigments in which chemically responsive dyes have been immobilized in a matrix of organically modified siloxanes (ormosils) have been prepared and characterized by AFM, TEM, EDS, and optical analysis. In typical chemical sensing applications, an array of 36 different porous ormosil pigments are deposited on polyethylene terephthalate (PET) film.

  13. Nanoscale porosity in pigments for chemical sensing.

    Science.gov (United States)

    Kemling, Jonathan W; Suslick, Kenneth S

    2011-05-01

    Porous pigments in which chemically responsive dyes have been immobilized in a matrix of organically modified siloxanes (ormosils) have been prepared and characterized by AFM, TEM, EDS, and optical analysis. In typical chemical sensing applications, an array of 36 different porous ormosil pigments are deposited on polyethylene terephthalate (PET) film.

  14. Dermatoscopic findings of pigmented purpuric dermatosis*

    Science.gov (United States)

    Ozkaya, Dilek Biyik; Emiroglu, Nazan; Su, Ozlem; Cengiz, Fatma Pelin; Bahali, Anil Gulsel; Yildiz, Pelin; Demirkesen, Cuyan; Onsun, Nahide

    2016-01-01

    Background Pigmented purpuric dermatosis is a chronic skin disorder of unknown aetiology characterised by symmetrical petechial and pigmented macules, often confined to the lower limbs. The aetiology of pigmented purpuric dermatosis is unknown. Dermatoscopy is a non-invasive diagnostic technique that allows the visualisation of morphological features invisible to the naked eye; it combines a method that renders the corneal layer of the skin translucent with an optical system that magnifies the image projected onto the retina. Objectives The aim of this study is to investigate the dermatoscopic findings of pigmented purpuric dermatosis. Methods This study enrolled patients diagnosed histopathologically with pigmented purpuric dermatosis who had dermatoscopic records. We reviewed the dermatoscopic images of PPD patients who attended the outpatient clinic in the Istanbul Dermatovenereology Department at the Bezmialem Vakıf University Medical Faculty. Results Dermatoscopy showed: coppery-red pigmentation (97%, n = 31) in the background, a brown network (34%, n = 11), linear vessels (22%, n = 7), round to oval red dots, globules, and patches (69%, n = 22; 75%, n = 24; 34%, n = 11; respectively), brown globules (26%, n = 8) and dots (53%, n = 17), linear brown lines (22%, n = 7), and follicular openings (13%, n = 4). Conclusion To our knowledge, this is the first study to report the dermatoscopy of pigmented purpuric dermatosis. In our opinion, dermatoscopy can be useful in the diagnosis of pigmented purpuric dermatosis. PMID:27828629

  15. Thin Layer Chromatography (TLC) of Chlorophyll Pigments.

    Science.gov (United States)

    Foote, Jerry

    1984-01-01

    Background information, list of materials needed, procedures used, and discussion of typical results are provided for an experiment on the thin layer chromatography of chlorophyll pigments. The experiment works well in high school, since the chemicals used are the same as those used in paper chromatography of plant pigments. (JN)

  16. Pigmented skin disorders: Evaluation and treatment

    NARCIS (Netherlands)

    Kroon, M.W.

    2015-01-01

    Pigmentary disorders are disturbances of human skin color. Minor changes in the cellular physiology of the skin can dramatically affect pigment production in positive or negative manner. In this these, associated diseases, therapeutical options and disease parameters for the pigmentation disorder

  17. Identification of an Alternative Splicing Product of the Otx2 Gene Expressed in the Neural Retina and Retinal Pigmented Epithelial Cells.

    Science.gov (United States)

    Kole, Christo; Berdugo, Naomi; Da Silva, Corinne; Aït-Ali, Najate; Millet-Puel, Géraldine; Pagan, Delphine; Blond, Frédéric; Poidevin, Laetitia; Ripp, Raymond; Fontaine, Valérie; Wincker, Patrick; Zack, Donald J; Sahel, José-Alain; Poch, Olivier; Léveillard, Thierry

    2016-01-01

    To investigate the complexity of alternative splicing in the retina, we sequenced and analyzed a total of 115,706 clones from normalized cDNA libraries from mouse neural retina (66,217) and rat retinal pigmented epithelium (49,489). Based upon clustering the cDNAs and mapping them with their respective genomes, the estimated numbers of genes were 9,134 for the mouse neural retina and 12,050 for the rat retinal pigmented epithelium libraries. This unique collection of retinal of messenger RNAs is maintained and accessible through a web-base server to the whole community of retinal biologists for further functional characterization. The analysis revealed 3,248 and 3,202 alternative splice events for mouse neural retina and rat retinal pigmented epithelium, respectively. We focused on transcription factors involved in vision. Among the six candidates suitable for functional analysis, we selected Otx2S, a novel variant of the Otx2 gene with a deletion within the homeodomain sequence. Otx2S is expressed in both the neural retina and retinal pigmented epithelium, and encodes a protein that is targeted to the nucleus. OTX2S exerts transdominant activity on the tyrosinase promoter when tested in the physiological environment of primary RPE cells. By overexpressing OTX2S in primary RPE cells using an adeno associated viral vector, we identified 10 genes whose expression is positively regulated by OTX2S. We find that OTX2S is able to bind to the chromatin at the promoter of the retinal dehydrogenase 10 (RDH10) gene.

  18. Identification of an Alternative Splicing Product of the Otx2 Gene Expressed in the Neural Retina and Retinal Pigmented Epithelial Cells

    Science.gov (United States)

    Kole, Christo; Berdugo, Naomi; Da Silva, Corinne; Aït-Ali, Najate; Millet-Puel, Géraldine; Pagan, Delphine; Blond, Frédéric; Poidevin, Laetitia; Ripp, Raymond; Fontaine, Valérie; Wincker, Patrick; Zack, Donald J.; Sahel, José-Alain; Poch, Olivier; Léveillard, Thierry

    2016-01-01

    To investigate the complexity of alternative splicing in the retina, we sequenced and analyzed a total of 115,706 clones from normalized cDNA libraries from mouse neural retina (66,217) and rat retinal pigmented epithelium (49,489). Based upon clustering the cDNAs and mapping them with their respective genomes, the estimated numbers of genes were 9,134 for the mouse neural retina and 12,050 for the rat retinal pigmented epithelium libraries. This unique collection of retinal of messenger RNAs is maintained and accessible through a web-base server to the whole community of retinal biologists for further functional characterization. The analysis revealed 3,248 and 3,202 alternative splice events for mouse neural retina and rat retinal pigmented epithelium, respectively. We focused on transcription factors involved in vision. Among the six candidates suitable for functional analysis, we selected Otx2S, a novel variant of the Otx2 gene with a deletion within the homeodomain sequence. Otx2S is expressed in both the neural retina and retinal pigmented epithelium, and encodes a protein that is targeted to the nucleus. OTX2S exerts transdominant activity on the tyrosinase promoter when tested in the physiological environment of primary RPE cells. By overexpressing OTX2S in primary RPE cells using an adeno associated viral vector, we identified 10 genes whose expression is positively regulated by OTX2S. We find that OTX2S is able to bind to the chromatin at the promoter of the retinal dehydrogenase 10 (RDH10) gene. PMID:26985665

  19. Dermatoscopy-guided therapy of pigmented basal cell carcinoma with imiquimod*

    Science.gov (United States)

    Husein-ElAhmed, Husein; Fernandez-Pugnaire, Maria Antonia

    2016-01-01

    BACKGROUND Dermatoscopy is a non-invasive diagnostic tool used to examine skin lesions with an optical magnification. It has been suggested as a useful tool for monitoring therapeutic response in lentigo maligna patients treated with imiquimod. OBJECTIVE To examine the accuracy of dermatoscopy as a tool to monitor the therapeutic response of pigmented basal cell carcinoma treated with imiquimod. METHOD The authors designed a prospective study. Patients with pigmented basal cell carcinoma were included and data regarding the dermatoscopy features were collected following the Menzies criteria, prior to initiating the imiquimod treatment. Subsequent dermatoscopic evaluations were performed at weeks 4 and 8, following imiquimod discontinuation. RESULTS Twenty lesions were included. The most common pigmented dermatoscopy features were large blue-grey ovoid nests (80%), followed by blue-grey globules (50%) and leaf-like areas (30%). No spoke wheel areas were observed. In 17 out of 20 patients, a response was noted during the first evaluation at 4 weeks, while the clearance was noted at the second check-up after 8 weeks. In two patients, the clearance was found at the initial evaluation at 4 weeks, while in one patient, the response remained unchanged. Blue-grey globules were the fastest to exhibit clearance (50% at week 4), followed by leaf-like areas (15%) and large blue-grey ovoid nests (6.25%). CONCLUSION According to our results, dermatoscopic evaluation enhances the accuracy in the assessment of the clinical response to imiquimod in pigmented basal cell carcinoma. PMID:28099598

  20. Genetic Analysis of Pigmentation in Cordyceps militaris

    Science.gov (United States)

    Shrestha, Bhushan; Choi, Sung-Keun; Kim, Ho-Kyoung; Kim, Tae-Woong

    2005-01-01

    Pigmentation of ascospore-derived isolates from seven different natural specimens of Cordyceps militaris EFCC C-5888, EFCC C-7159, EFCC C-7833, EFCC C-7991, EFCC C-8021, EFCC C-8023 and EFCC C-8179 was observed on the plates of Sabouraud Dextrose agar plus Yeast Extract at 25℃ under continuous illumination (500 lux). Pigmentation of the wild-type isolates of C. militaris was diverse ranging from yellowish white to orange, while white color was believed as a mutant. Inheritance of pigmentation was found to be controlled by both parental isolates when F1 progeny were analyzed. Pigmentation and mating type were shown to be either i