LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 4 of total 4

Search options

  1. Article ; Online: Author Correction: Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma.

    Sato, Kota / Saigusa, Daisuke / Kokubun, Taiki / Fujioka, Amane / Feng, Qiwei / Saito, Ritsumi / Uruno, Akira / Matsukawa, Naomi / Ohno-Oishi, Michiko / Kunikata, Hiroshi / Yokoyama, Yu / Yasuda, Masayuki / Himori, Noriko / Omodaka, Kazuko / Tsuda, Satoru / Maekawa, Shigeto / Yamamoto, Masayuki / Nakazawa, Toru

    npj aging

    2024  Volume 10, Issue 1, Page(s) 8

    Language English
    Publishing date 2024-01-20
    Publishing country England
    Document type Published Erratum
    ISSN 2731-6068
    ISSN (online) 2731-6068
    DOI 10.1038/s41514-024-00137-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: Cyclin-Dependent Kinase Inhibitor 2b Mediates Excitotoxicity-Induced Death of Retinal Ganglion Cells.

    Tawarayama, Hiroshi / Feng, Qiwei / Murayama, Namie / Suzuki, Noriyuki / Nakazawa, Toru

    Investigative ophthalmology & visual science

    2019  Volume 60, Issue 13, Page(s) 4479–4488

    Abstract: Purpose: Glutamate excitotoxicity seems to contribute to retinal ganglion cell (RGC) death in various eye diseases, but the underlying molecular mechanisms are not fully understood. We studied the roles of cyclin-dependent kinase inhibitors Cdkn2a and ... ...

    Abstract Purpose: Glutamate excitotoxicity seems to contribute to retinal ganglion cell (RGC) death in various eye diseases, but the underlying molecular mechanisms are not fully understood. We studied the roles of cyclin-dependent kinase inhibitors Cdkn2a and Cdkn2b, known as cellular stress-related senescence markers, in N-methyl-d-aspartate (NMDA)-induced RGC death.
    Methods: Gene expression was analyzed using quantitative reverse transcription (qRT)-PCR, in situ hybridization, and immunochemistry. Cdkn2a and Cdkn2b gain- and loss-of-function experiments were performed using the adeno-associated virus type 2 (AAV2)-mediated gene delivery system. AAV2-CRISPR-Cas9-mediated knockout of Cdkn2a or Cdkn2b was validated using cultured cells by T7 endonuclease I assay and Western blot analysis. The effects of altered expression of Cdkn2a and Cdkn2b on NMDA-induced RGC death were evaluated by quantification of RNA binding protein with multiple splicing (Rbpms)-immunoreactive RGCs.
    Results: Intravitreal NMDA injection resulted in upregulation of Cdkn2a and Cdkn2b expression in RGCs of the mouse retina. AAV2-mediated overexpression of Cdkn2b led to increased expression of Cdkn2a in RGCs, but not vice versa. Overexpression of Cdkn2b, but not Cdkn2a, resulted in a further reduction in RGC viability in NMDA-injected retinas. However, excessive levels of Cdkn2a or Cdkn2b had no effect on RGC viability in healthy mice. AAV2-CRISPR-Cas9-mediated knockout of either Cdkn2a or Cdkn2b attenuated NMDA-induced RGC death.
    Conclusions: Cdkn2a and Cdkn2b have pivotal roles in the regulation of excitotoxic RGC degeneration under NMDA-induced pathologic conditions. Our findings imply that Cdkn2a and Cdkn2b are novel therapeutic targets for ocular diseases displaying excitotoxicity-induced neuronal degeneration.
    MeSH term(s) Animals ; Blotting, Western ; CRISPR-Cas Systems ; Cell Death ; Cyclin-Dependent Kinase Inhibitor p15/physiology ; Cyclin-Dependent Kinase Inhibitor p16/physiology ; Excitatory Amino Acid Agonists/toxicity ; Immunochemistry ; In Situ Hybridization ; Intravitreal Injections ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Methylaspartate/toxicity ; Parvovirinae/genetics ; Retinal Ganglion Cells/drug effects ; Retinal Ganglion Cells/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection
    Chemical Substances Cdkn2a protein, mouse ; Cdkn2b protein, mouse ; Cyclin-Dependent Kinase Inhibitor p15 ; Cyclin-Dependent Kinase Inhibitor p16 ; Excitatory Amino Acid Agonists ; N-Methylaspartate (6384-92-5)
    Language English
    Publishing date 2019-10-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.19-27396
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Reduced glutathione level in the aqueous humor of patients with primary open-angle glaucoma and normal-tension glaucoma.

    Sato, Kota / Saigusa, Daisuke / Kokubun, Taiki / Fujioka, Amane / Feng, Qiwei / Saito, Ritsumi / Uruno, Akira / Matsukawa, Naomi / Ohno-Oishi, Michiko / Kunikata, Hiroshi / Yokoyama, Yu / Yasuda, Masayuki / Himori, Noriko / Omodaka, Kazuko / Tsuda, Satoru / Maekawa, Shigeto / Yamamoto, Masayuki / Nakazawa, Toru

    npj aging

    2023  Volume 9, Issue 1, Page(s) 28

    Abstract: Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass ... ...

    Abstract Glaucoma is a leading cause of blindness worldwide in older people. Profiling the aqueous humor, including the metabolites it contains, is useful to understand physiological and pathological conditions in the eye. In the current study, we used mass spectrometry (MS) to characterize the aqueous humor metabolomic profile and biological features of patients with glaucoma. Aqueous humor samples were collected during trabeculectomy surgery or cataract surgery and analyzed with global metabolomics. We included 40 patients with glaucoma (32 with POAG, 8 with NTG) and 37 control subjects in a discovery study. VIP analysis revealed five metabolites that were elevated and three metabolites that were reduced in the glaucoma patients. The identified metabolomic profile had an area under the receiver operating characteristic curve of 0.953. Among eight selected metabolites, the glutathione level was significantly decreased in association with visual field defects. Moreover, in a validation study to confirm the reproducibility of our findings, the glutathione level was reduced in NTG and POAG patients compared with a cataract control group. Our findings demonstrate that aqueous humor profiling can help to diagnose glaucoma and that various aqueous humor metabolites are correlated with clinical parameters in glaucoma patients. In addition, glutathione is clearly reduced in the aqueous humor of glaucoma patients with both IOP-dependent and IOP-independent disease subtypes. These findings indicate that antioxidant agents in the aqueous humor reflect glaucomatous optic nerve damage and that excessive oxidative stress may be involved in the pathogenesis of glaucoma.
    Language English
    Publishing date 2023-11-21
    Publishing country England
    Document type Journal Article
    ISSN 2731-6068
    ISSN (online) 2731-6068
    DOI 10.1038/s41514-023-00124-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Ecel1 Knockdown With an AAV2-Mediated CRISPR/Cas9 System Promotes Optic Nerve Damage-Induced RGC Death in the Mouse Retina.

    Sato, Kota / Shiga, Yukihiro / Nakagawa, Yurika / Fujita, Kosuke / Nishiguchi, Koji M / Tawarayama, Hiroshi / Murayama, Namie / Maekawa, Shigeto / Yabana, Takeshi / Omodaka, Kazuko / Katayama, Shota / Feng, Qiwei / Tsuda, Satoru / Nakazawa, Toru

    Investigative ophthalmology & visual science

    2018  Volume 59, Issue 10, Page(s) 3943–3951

    Abstract: Purpose: To assess the therapeutic potential of endothelin-converting enzyme-like 1 (Ecel1) in a mouse model of optic nerve crush.: Methods: Ecel1 expression was evaluated with real time quantitative (qRT)-PCR, Western blotting, and ... ...

    Abstract Purpose: To assess the therapeutic potential of endothelin-converting enzyme-like 1 (Ecel1) in a mouse model of optic nerve crush.
    Methods: Ecel1 expression was evaluated with real time quantitative (qRT)-PCR, Western blotting, and immunohistochemistry in mouse retinas after optic nerve crush. Vinblastine administration to the optic nerve and the intravitreal injection of N-methyl-d-aspartate (NMDA) were used to assess Ecel1 gene expression. Ecel1 was deleted with an adeno-associated viral (AAV) clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas9 system, and retinal ganglion cell (RGC) survival was investigated with retrograde labeling, qRT-PCR, and visual evoked potential.
    Results: Optic nerve crush induced Ecel1 expression specifically in the RGCs, peaking on day 4 after optic nerve crush. Ecel1 gene expression was induced by the vinblastine-induced inhibition of axonal flow, but not by NMDA-induced excitotoxicity, even though both are triggers of RGC death. Knockdown of Ecel1 promoted the loss of RGCs after optic nerve crush.
    Conclusions: Our data suggest that Ecel1 induction is part of the retinal neuroprotective response to axonal injury in mice. These findings might provide insight into novel therapeutic targets for the attenuation of RGC damage, such as occurs in traumatic optic neuropathy.
    MeSH term(s) Animals ; CRISPR-Cas Systems/physiology ; Cell Survival ; Evoked Potentials, Visual/physiology ; Immunohistochemistry ; Metalloendopeptidases/metabolism ; Metalloendopeptidases/physiology ; Mice ; Mice, Knockout ; N-Methylaspartate/pharmacology ; Nerve Crush ; Neuroprotection/physiology ; Optic Nerve Injuries/metabolism ; Optic Nerve Injuries/physiopathology ; Real-Time Polymerase Chain Reaction ; Retina/metabolism ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/pathology ; Vinblastine/pharmacology
    Chemical Substances Vinblastine (5V9KLZ54CY) ; N-Methylaspartate (6384-92-5) ; Ecel1 protein, mouse (EC 3.4.24.-) ; Metalloendopeptidases (EC 3.4.24.-)
    Language English
    Publishing date 2018-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391794-0
    ISSN 1552-5783 ; 0146-0404
    ISSN (online) 1552-5783
    ISSN 0146-0404
    DOI 10.1167/iovs.18-23784
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top