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Role of the ETB receptor in retinal ganglion cell death in glaucoma.

Role of the ETB receptor in retinal ganglion cell death in glaucoma. Research Abstract Details 

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  • Role of the ETB receptor in retinal ganglion cell death in glaucoma. Abstract Text:

    Recent observations suggest that the vasoactive peptide endothelin-1 (ET-1) may be an important contributor to the etiology of glaucoma. ET-1 administration has been shown to produce optic nerve axonal loss and apoptosis of retinal ganglion cells. Ocular ET-1 levels are elevated in aqueous humor in response to elevated intraocular pressure both in glaucoma patients and in animal models of glaucoma; however, the precise mechanisms by which ET-1 mediates glaucomatous optic neuropathy are not clear. Presently we report that ET-1-mediated apoptosis was markedly attenuated in ETB receptor-deficient rats, suggesting a key role for ETB receptors in apoptosis of retinal ganglion cells by ET-1 treatment. Using virally transformed rat retinal ganglion cells (RGC-5 cells), we found that ET-1 (100 nmol/L) treatment produced apoptotic changes in these cells that was determined by flow cytometric analyses, release of mitochondrial cytochrome c to the cytosol, and increased phosphorylation of c-Jun N-terminal kinase. Pretreatment with the ETB-receptor antagonist BQ788 (1 micromol/L) was able to significantly attenuate ET-1-mediated apoptosis in RGC-5 cells. ET-1-mediated apoptotic changes in RGC-5 cells were associated with ETB-receptor activation and were accompanied by a significant upregulation of ETB-receptor expression. These studies suggest that ocular ET-1 acts through ETB receptors to mediate apoptosis of retinal ganglion cells, a key event in glaucoma and related optic neuropathies.

    Role of the ETB receptor in retinal ganglion cell death in glaucoma. Publishing Authors By Initials

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    PUBMED ID PMID:

    MEDLINE DATE:

    Role of the ETB receptor in retinal ganglion cell death in glaucoma. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Canadian journal of physiology and pharmacology

    VOLUME: 86

    Page Numbers: 380-93

    Journal Abbreviation: Can. J. Physiol. Pharmacol.

    ISSN: 0008-4212

    DAY: 26

    MONTH: Jun

    YEAR: 2008

    Role of the ETB receptor in retinal ganglion cell death in glaucoma. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 372712

    Role of the ETB receptor in retinal ganglion cell death in glaucoma. Keywords Mesh Terms:

    KEYWORDS: Up-Regulation

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Role of the ETB receptor in retinal ganglion cell death in glaucoma. Information

    Substance Name: JNK Mitogen-Activated Protein Kinases

    Registry Number: EC 2.7.1.37

    Grant and Affiliation Information for Role of the ETB receptor in retinal ganglion cell death in glaucoma.

    AFFILIATION: Department of Pharmacology and Neuroscience, UNT Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA. rkrishna@hsc.unt.edu

    Country: Canada

    Canada Research PublicationCanada Research Publication

    AGENCY: United States NEI

    GRANT: R01 EY11979

    ACRONYM: EY

    MEDLINETA: Can J Physiol Pharmacol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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