Anja-Kristina Brust¹, Holger K. Ulbrich², Gail M. Seigel³, Norbert Pfeiffer¹ and Franz H. Grus¹

¹Department of Ophthalmology, Johannes Gutenberg University of Mainz, Germany. ²Institute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Johannes Gutenberg University of Mainz, Germany. ³Ross Eye Institute, Department of Ophthalmology, University of Buffalo, NY, U.S.A.

Abstract

Glaucoma is characterized by a loss of retinal ganglion cells (RGC) which is associated with a decrease of visual function. Neuroprotective agents as a new therapeutic strategy could prevent the remaining neurons from apoptotic cell death. Previous studies have shown the involvement of the Cyclooxygenase (COX)-2 signalling in the apoptotic death of neurons. Herein we investigated the neuroprotective effect of COX-1/COX-2- and selective COX-2- inhibitors on apoptotic. R28, a neuroretinal cell line and determined the PGE₂ levels by ELISA. Furthermore we investigated differences in protein expression in the cells after exposure to elevated pressure compared to untreated cells by ProteinChip analysis.

In addition, a protein profiling study of the cells after exposure to elevated pressure was performed. The protein expression profiles were measured by SELDI-TOF (Surface Enhanced Laser Desorption/Ionization-time of flight) Protein Chips. The protein identification was performed by mass spectrometry (MS).

It could be shown that COX-2 inhibition significantly prevented the cells from apoptosis and reduced the PGE₂ concentrations. Selective COX-2 inhibitors were significant more potent than non-selective inhibitors or COX-1 inhibitors. We found differently expressed protein patterns in neuroretinal cells cultured at atmospheric pressure compared to those cells exposed to elevated pressure with or without celecoxib respectively. We identified three biomarkers, ubiquitin, HSP10 and NDKB, which were differently expressed in the groups. However, our data indicates a distinct neuroprotective effect of COX-2 inhibition. The local treatment with selective COX-2 inhibitors might provide an innovative strategy of therapeutic intervention for glaucoma.