Millipore Sigma Vibrant Logo
 

retinal+degeneration


204 Results Búsqueda avanzada  
Mostrar
Productos (0)
Documentos (202)
Páginas (2)

Acote sus resultados Utilice los filtros siguientes para refinar su búsqueda

Tipo de documento

  • (202)
¿No encuentra lo que está buscando?
Póngase en contacto con
el Servicio de Atención
al Cliente

 
¿Necesita ayuda para encontrar un documento?

  • The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: identification of curcumin as a protective agent for retinal pigme ... 25136316

    Age-related macular degeneration (AMD) is one retinal aging process that may lead to irreversible vision loss in the elderly. Its pathogenesis remains unclear, but oxidative stress inducing retinal pigment epithelial (RPE) cells damage is perhaps responsible for the aging sequence of retina and may play an important role in macular degeneration. In this study, we have reprogrammed T cells from patients with dry type AMD into induced pluripotent stem cells (iPSCs) via integration-free episomal vectors and differentiated them into RPE cells that were used as an expandable platform for investigating pathogenesis of the AMD and in-vitro drug screening. These patient-derived RPEs with the AMD-associated background (AMD-RPEs) exhibited reduced antioxidant ability, compared with normal RPE cells. Among several screened candidate drugs, curcumin caused most significant reduction of ROS in AMD-RPEs. Pre-treatment of curcumin protected these AMD-RPEs from H2O2-induced cell death and also increased the cytoprotective effect against the oxidative stress of H2O2 through the reduction of ROS levels. In addition, curcumin with its versatile activities modulated the expression of many oxidative stress-regulating genes such as PDGF, VEGF, IGFBP-2, HO1, SOD2, and GPX1. Our findings indicated that the RPE cells derived from AMD patients have decreased antioxidative defense, making RPE cells more susceptible to oxidative damage and thereby leading to AMD formation. Curcumin represented an ideal drug that can effectively restore the neuronal functions in AMD patient-derived RPE cells, rendering this drug an effective option for macular degeneration therapy and an agent against aging-associated oxidative stress.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB5922

  • Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration. 26527153

    Reactive microglia are commonly seen in retinal degenerative diseases, and neurotoxic microglia responses can contribute to photoreceptor cell death. We and others have previously shown that translocator protein (18 kDa) (TSPO) is highly induced in retinal degenerations and that the selective TSPO ligand XBD173 (AC-5216, emapunil) exerts strong anti-inflammatory effects on microglia in vitro and ex vivo. Here, we investigated whether targeting TSPO with XBD173 has immuno-modulatory and neuroprotective functions in two mouse models of acute retinal degeneration using bright white light exposure.BALB/cJ and Cx3cr1(GFP/+) mice received intraperitoneal injections of 10 mg/kg XBD173 or vehicle for five consecutive days, starting 1 day prior to exposure to either 15,000 lux white light for 1 h or 50,000 lux focal light for 10 min, respectively. The effects of XBD173 treatment on microglia and Müller cell reactivity were analyzed by immuno-stainings of retinal sections and flat mounts, fluorescence-activated cell sorting (FACS) analysis, and mRNA expression of microglia markers using quantitative real-time PCR (qRT-PCR). Optical coherence tomography (OCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, and morphometric analyses were used to quantify the extent of retinal degeneration and photoreceptor apoptosis.Four days after the mice were challenged with bright white light, a large number of amoeboid-shaped alerted microglia appeared in the degenerating outer retina, which was nearly completely prevented by treatment with XBD173. This treatment also down-regulated the expression of TSPO protein in microglia but did not change the TSPO levels in the retinal pigment epithelium (RPE). RT-PCR analysis showed that the microglia/macrophage markers Cd68 and activated microglia/macrophage whey acidic protein (Amwap) as well as the pro-inflammatory genes Ccl2 and Il6 were reduced after XBD173 treatment. Light-induced degeneration of the outer retina was nearly fully blocked by XBD173 treatment. We further confirmed these findings in an independent mouse model of focal light damage. Retinas of animals receiving XBD173 therapy displayed significantly more ramified non-reactive microglia and more viable arrestin-positive cone photoreceptors than vehicle controls.Targeting TSPO with XBD173 effectively counter-regulates microgliosis and ameliorates light-induced retinal damage, highlighting a new pharmacological concept for the treatment of retinal degenerations.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB302
    Nombre del producto:
    Anti-Glutamine Synthetase Antibody, clone GS-6

  • Novel compstatin family peptides inhibit complement activation by drusen-like deposits in human retinal pigmented epithelial cell cultures. 23954241

    We have used a novel human retinal pigmented epithelial (RPE) cell-based model that mimics drusen biogenesis and the pathobiology of age-related macular degeneration to evaluate the efficacy of newly designed peptide inhibitors of the complement system. The peptides belong to the compstatin family and, compared to existing compstatin analogs, have been optimized to promote binding to their target, complement protein C3, and to enhance solubility by improving their polarity/hydrophobicity ratios. Based on analysis of molecular dynamics simulation data of peptide-C3 complexes, novel binding features were designed by introducing intermolecular salt bridge-forming arginines at the N-terminus and at position -1 of N-terminal dipeptide extensions. Our study demonstrates that the RPE cell assay has discriminatory capability for measuring the efficacy and potency of inhibitory peptides in a macular disease environment.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB947
    Nombre del producto:
    Anti-Apolipoprotein E Antibody

  • Progressive degeneration of retinal and superior collicular functions in mice with sustained ocular hypertension. 25722210

    We investigated the progressive degeneration of retinal and superior collicular functions in a mouse model of sustained ocular hypertension.Focal laser illumination and injection of polystyrene microbeads were used to induce chronic ocular hypertension. Retinal ganglion cell (RGC) loss was characterized by in vivo optical coherence tomography (OCT) and immunohistochemistry. Retinal dysfunction was also monitored by the full-field ERG. Retinal ganglion cell light responses were recorded using a 256-channel multielectrode array (MEA), and RGC subtypes were characterized by noncentered spike-triggered covariance (STC-NC) analysis. Single-unit extracellular recordings from superficial layers of the superior colliculus (SC) were performed to examine the receptive field (RF) properties of SC neurons.The elevation of intraocular pressure (IOP) lasted 4 months in mice treated with a combination of laser photocoagulation and microbead injection. Progressive RGC loss and functional degeneration were confirmed in ocular hypertensive (OHT) mice. These mice had fewer visually responsive RGCs than controls. Using the STC-NC analysis, we classified RGCs into ON, OFF, and ON-OFF functional subtypes. We showed that ON and OFF RGCs were more susceptible to the IOP elevation than ON-OFF RGCs. Furthermore, SC neurons of OHT mice had weakened responses to visual stimulation and exhibited mismatched ON and OFF subfields and irregular RF structure.We demonstrated that the functional degeneration of RGCs is subtype-dependent and that the ON and OFF pathways from the retina to the SC were disrupted. Our study provides a foundation to investigate the mechanisms underlying the progressive vision loss in experimental glaucoma.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB1585
    Nombre del producto:
    Anti-Brn-3a Antibody, POU-domain protein, clone 5A3.2

  • Constant illumination causes spatially discrete dopamine depletion in the normal and degenerate retina. 17223011

    A fully competent retinal dopamine system underpins normal visual function. Although this system is known to be compromised both prior to and during retinal degeneration, the spatial dynamics of dopamine turnover within the degenerate retina are at present unknown. Here, using immunohistochemistry for dopamine in combination with quantitative optical density measurements, we reveal a global decline in retinal dopamine levels in the light adapted RCS dystrophic rat, which is restricted to plexiform layers in the dark. Pharmacological blockade of dopamine production with the drug alpha-methyl-p-tyrosine (AMPT) allows the direct visualisation of dopamine depletion in normal and degenerate retina in response to constant illumination. In normal retinae this effect is spatially discrete, being undetectable in perikarya and specific to amacrine cell fibres in sublamina 1 of the inner plexiform layer. A similar response was observed in the retinae of dystrophic rats but with a reduction in amplitude of approximately 50%. It is suggested that the pattern of dopamine depletion observed in rat retina may reflect an AMPT-resistant pool of perikaryal dopamine and/or a reduction in extrasynaptic release of this neurotransmitter in response to illumination in vivo. We conclude that the visualisation of dopamine depletion reported here represents a release of this neurotransmitter in the response to light. Turnover of dopamine in the dystrophic retina is discussed in the context of surviving photoreceptors, including the intrinsically photosensitive melanopsin ganglion cells of the inner retina.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB122S
    Nombre del producto:

  • Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene. 20691256

    Generalized progressive retinal atrophy (gPRA) belongs to a group of inherited retinal diseases which are associated with gradual vision loss in various dog breeds, including the Irish Glen of Imaal Terrier (GIT). By genome-wide homozygosity mapping using SNP arrays and fine mapping of candidate regions, we assigned the gPRA candidate locus in this breed to canine chromosome 16. The respective region is syntenic with human chromosome 8 comprising the ADAM metallopeptidase domain 9 (ADAM9) gene. ADAM9 represents a strong candidate gene for canine retinal disease because mutations have previously been shown to cause autosomal recessively inherited human cone-rod dystrophy, a retinal disorder affecting photoreceptor function. Sequence analysis of ADAM9 in affected and carrier GITs revealed a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon. This mutation was absent from 34 other dog breeds. A variable and, at times, very late onset of gPRA was confirmed in GITs by a relatively mild retinal degeneration at an advanced age. Hence, the identification of the genetic defect underlying gPRA in the GIT represents a suitable model for cone-rod dystrophy of humans, with superior potential to elucidate functional consequences of the recently described null mutations in the human ADAM9 gene.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB5316
    Nombre del producto:
    Anti-Rhodopsin Antibody, clone RET-P1

  • The potential role of amyloid beta in the pathogenesis of age-related macular degeneration. 16167083

    Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid beta (Abeta) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Abeta on cultured human RPE cells as well as ocular findings in neprilysin gene-disrupted mice, which leads to an increased deposition Abeta. The results showed that Abeta treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Abeta-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene-disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Abeta accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Abeta reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB348
    Nombre del producto:
    Anti-APP A4 Antibody, a.a. 66-81 of APP {NT}, clone 22C11

  • Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin. 17525210

    PURPOSE: To characterize the reactions of retinal glial cells (astrocytes and Müller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP-/-Vim-/-) and to determine the role of glial cells in retinal detachment (RD)-induced photoreceptor degeneration. METHODS: RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and GFAP-/-Vim-/- mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness. RESULTS: RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP-/-Vim-/- mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice. CONCLUSIONS: The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage.
    Tipo de documento:
    Referencia
    Referencia del producto:
    S7110
    Nombre del producto:
    ApopTag® Fluorescein In Situ Apoptosis Detection Kit

  • Rac1 selective activation improves retina ganglion cell survival and regeneration. 23734197

    In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs) do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB360
    Nombre del producto:
    Anti-Glial Fibrillary Acidic Protein Antibody, clone GA5

  • Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations. 19255154

    To characterize the retinal histopathology in carriers of X-linked progressive retinal atrophy (XLPRA1 and XLPRA2), two canine models of X-linked retinitis pigmentosa caused, respectively, by a stop and a frameshift mutation in RPGRORF15.Retinas of XLPRA2 and XLPRA1 carriers of different ages were processed for morphologic evaluation, TUNEL assay, and immunohistochemistry. Cell-specific markers were used to examine retinal remodeling events.A mosaic pattern composed of patches of diseased and normal retina was first detected in XLPRA2 carriers at 4.9 weeks of age. A peak of photoreceptor cell death led to focal rod loss; however, in these patches an increased density of cones was found to persist over time. Patches of disease gradually disappeared so that by 39 weeks of age the overall retinal morphology, albeit thinner, had improved lamination. In older XLPRA2 carriers (greater than or=8.8 years), extended regions of severe degeneration occurred in the peripheral/mid-peripheral retina. In XLPRA1 carriers, opsin mislocalization and rare events of rod death were detected by TUNEL assay at 20 weeks of age; however, only patchy degeneration was seen by 1.4 years and was still apparent at 7.8 years.The time of onset and the progression of the disease differed between the two models. In the early-onset form (XLPRA2) the morphologic appearance of the retinal mosaic changed as a function of age, suggesting that structural plasticity persists in the early postnatal canine retina as mutant photoreceptors die. In the late-onset form (XLPRA1), patches of disease persisted until later ages.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo