May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Neuroprotective Effects Of Cyclooxygenase Inhibitors On Apoptotic Retinal Ganglion Cells
Author Affiliations & Notes
  • K. Brust
    Ophthalmology, University Hospital, Mainz, Germany
  • H. Ulbrich
    Institute of Pharmacy, University, Mainz, Germany
  • G. Seigel
    Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY
  • N. Pfeiffer
    Ophthalmology, University Hospital, Mainz, Germany
  • F. Grus
    Ophthalmology, University Hospital, Mainz, Germany
  • Footnotes
    Commercial Relationships  K. Brust, None; H. Ulbrich, None; G. Seigel, None; N. Pfeiffer, None; F. Grus, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 404. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      K. Brust, H. Ulbrich, G. Seigel, N. Pfeiffer, F. Grus; Neuroprotective Effects Of Cyclooxygenase Inhibitors On Apoptotic Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):404.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Glaucomatous optic neuropathy is characterized by a loss of retinal ganglion cells which is associated with the decrease of visual function. Neuroprotective agents could prevent the remaining neurons from apoptotic cell death. Previous studies have shown that induction of the Cyclooxygenase–2 (COX–2) signaling cascade may sensitize neocortical and amnion–derived cells to apoptotic death. In our study we investigated the neuroprotective effect of different drugs, in particular COX–1/COX–2– and selective COX–2–inhibitors on apoptotic retinal ganglion cells (R28).

Methods: : To study the effect of the substances we induced apoptosis to a retinal ganglion cell line (R28) by serum deprivation for 48 hours or by exposing the cells to elevated hydrostatic pressure for the same time period respectively. The effects of several unselective COX–1/COX–2– and selective COX–2 inhibitors was determined in different concentrations of the drugs and compared to untreated apoptotic control cells. The reduction in cell viability was measured by the colorimetric WST–1 test. Furthermore, in order to assess the underlying mechanisms of possible neuroprotective effects of these drugs, a protein profiling study of the retinal ganglion cells was performed. The protein expression profiles were measured by SELDI–TOF Protein Chips using different surfaces.

Results: : We demonstrated that different COX–2 inhibitors prevent retinal ganglion cells from apoptosis in a dose dependent manner. In the clinical relevant concentration of 10µM celecoxib and DFU showed the maximal neuroprotective effects (81% and 38% more surviving cells compared to serum–free treated cells, P<0.001) Diclofenac, which inhibits both COX isoforms could prevent 26% of the cells from dying. The weakest effect revealed meloxicam (14%) (P<0.001) which is an unselective inhibitor of the COX isoforms (P<0.001) COX–2 inhibitors seem to be significantly more potent than inhibitors of COX–1. The Protein Chip analysis revealed significant changes in protein expression due to the different COX inhibitors in the molecular range of 5 to 20 kDa.

Conclusions: : Treatment of apoptotic retinal ganglion cells with COX–2 selective inhibitors could increase the amount of surviving retinal ganglion cells in a dose dependent manner and could provide new opportunities for the neuroprotective treatment of apoptosis mediated diseases such as glaucoma.

Keywords: ganglion cells • apoptosis/cell death • neuroprotection 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.