VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina
Article first published online: 8 JAN 2010
© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol
Volume 89, Issue 7, pages 670–675, November 2011
How to Cite
Teuchner, B., Dimmer, A., Humpel, C., Amberger, A., Fischer-Colbrie, R., Nemeth, J., Waschek, J. A., Kieselbach, G., Kralinger, M., Schmid, E., Bechrakis, N. and Troger, J. (2011), VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina. Acta Ophthalmologica, 89: 670–675. doi: 10.1111/j.1755-3768.2009.01828.x
- Issue published online: 8 JAN 2010
- Article first published online: 8 JAN 2010
- Received on July 1st, 2009. Accepted on November 19th, 2009.
Purpose: To evaluate the effect of intravitreal injection of N-methyl-D-aspartate (NMDA) on brain-derived neurotrophic factor (BDNF), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), vasoactive intestinal peptide (VIP) and the VIP-associated glial protein activity-dependent neuroprotective protein (ADNP) in the rat retina. These elements have well-documented neuroprotective properties and may thus be integrated in endogenous neuroprotective mechanisms in the retina which break down in NMDA excitotoxicity.
Methods: A volume of 2 μl of 100 nmol NMDA was intravitreally injected into one eye of rats, the untreated eye served as a control. Time-dependent effects of NMDA on VIP, PACAP-38 and BDNF were detected by radioimmunoassay and ELISA, and the effect on the expression of VIP, PACAP-38 and ADNP was evaluated by quantitative RT-PCR 20 days after NMDA injection. Topical flunarizine served to find out whether the effect of NMDA is counteracted.
Results: Compared to PACAP-38, VIP levels significantly decreased on days 1, 7, 14, 28 and 56 after NMDA injection indicating that VIPergic cells are more vulnerable than PACAP-38-expressing cells. The expression of VIP and ADNP but not of PACAP-38 was found to be reduced, and application of topical flunarizine counteracted the decrease of VIP. BDNF levels significantly increased after days 1 and 3.
Conclusion: The early upregulation of BDNF seems to act neuroprotectively and leads to a delay of ganglion cell loss. Although there is no direct evidence, the decrease of VIP and ADNP – the consequence of the presence of NMDA receptors on these peptide-expressing cells – might contribute to the breakdown of endogenous neuroprotective mechanisms given that the decrease of the VIP-related ADNP runs in parallel with the decrease of VIP. Activating and maintaining these mechanisms must be the primary aim in the therapy of diseases with retinal neuronal degeneration.