Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2013 May 14;8(5):e64262. doi: 10.1371/journal.pone.0064262. Print 2013.

The protective effects of the proteasome inhibitor bortezomib (velcade) on ischemia-reperfusion injury in the rat retina.

Author information

  • 1Department of Ophthalmology, Far Eastern Memorial Hospital, Ban-Chiao, Taipei, Taiwan.

Abstract

PURPOSE:

To evaluate the protective effects of bortezomib (Velcade) on ischemia-reperfusion (IR) injury in the rat retina.

METHODS:

The rats were randomized to receive treatment with saline, low-dose bortezomib (0.05 mg/kg), or high-dose bortezomib (0.2 mg/kg) before the induction of IR injury. Electroretinography (ERG) was used to assess functional changes in the retina. The expression of inflammatory mediators (iNOS, ICAM-1, MCP-1, TNF-α), anti-oxidant proteins (heme oxygenase, thioredoxin, peroxiredoxin), and pro-apoptotic proteins (p53, bax) were quantified by PCR and western blot analysis. An immunofluorescence study was performed to detect the expression of iNOS, oxidative markers (nitrotyrosine, 8-OHdG, acrolein), NF-κB p65, and CD 68. Apoptosis of retinal cells was labeled with in situ TUNEL staining. Neu-N staining was performed in the flat-mounted retina to evaluate the density of retinal ganglion cells.

RESULTS:

ERG showed a decreased b-wave after IR injury, and pretreatment with bortezomib, especially the high dosage, reduced the functional impairment. Bortezomib successfully reduced the elevation of inflammatory mediators, anti-oxidant proteins, pro-apoptotic proteins and oxidative markers after IR insult in a dose-dependent manner. In a similar fashion, NF-κB p65- and CD 68-positive cells were decreased by bortezomib treatment. Retinal cell apoptosis in each layer was attenuated by bortezomib. The retinal ganglion cell density was markedly decreased in the saline and low-dose bortezomib groups but was not significantly changed in the high-dose bortezomib group.

CONCLUSIONS:

Bortezomib had a neuro-protective effect in retinal IR injury, possibly by inhibiting the activation of NF-κB related to IR insult and reducing the inflammatory signals and oxidative stress in the retina.

PMID:
23691186
[PubMed - indexed for MEDLINE]
PMCID:
PMC3653862
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk