PMID- 20064115 OWN - NLM STAT- MEDLINE DCOM- 20120203 LR - 20141120 IS - 1755-3768 (Electronic) IS - 1755-375X (Linking) VI - 89 IP - 7 DP - 2011 Nov TI - VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina. PG - 670-5 LID - 10.1111/j.1755-3768.2009.01828.x [doi] AB - 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 mul 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. CI - (c) 2010 The Authors. Journal compilation (c) 2010 Acta Ophthalmol. FAU - Teuchner, Barbara AU - Teuchner B AD - Department of Ophthalmology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Dimmer, Andreas AU - Dimmer A FAU - Humpel, Christian AU - Humpel C FAU - Amberger, Albert AU - Amberger A FAU - Fischer-Colbrie, Reiner AU - Fischer-Colbrie R FAU - Nemeth, Jozsef AU - Nemeth J FAU - Waschek, James A AU - Waschek JA FAU - Kieselbach, Gerhard AU - Kieselbach G FAU - Kralinger, Martina AU - Kralinger M FAU - Schmid, Eduard AU - Schmid E FAU - Bechrakis, Nikolaos AU - Bechrakis N FAU - Troger, Josef AU - Troger J LA - eng PT - Journal Article DEP - 20100108 PL - England TA - Acta Ophthalmol JT - Acta ophthalmologica JID - 101468102 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (Nerve Tissue Proteins) RN - 0 (Neuropeptides) RN - 0 (Oligopeptides) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (activity-dependent neurotrophic factor) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - 6384-92-5 (N-Methylaspartate) RN - R7PLA2DM0J (Flunarizine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Excitatory Amino Acid Agonists/*toxicity MH - Flunarizine/administration & dosage MH - Intravitreal Injections MH - Male MH - N-Methylaspartate/*toxicity MH - Nerve Tissue Proteins/genetics/*metabolism MH - Neuropeptides/genetics/*metabolism MH - Oligopeptides MH - Pituitary Adenylate Cyclase-Activating Polypeptide/genetics/*metabolism MH - Radioimmunoassay MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - Retina/*drug effects/metabolism MH - Up-Regulation MH - Vasoactive Intestinal Peptide/genetics/*metabolism EDAT- 2010/01/13 06:00 MHDA- 2012/02/04 06:00 CRDT- 2010/01/13 06:00 PHST- 2010/01/13 06:00 [entrez] PHST- 2010/01/13 06:00 [pubmed] PHST- 2012/02/04 06:00 [medline] AID - AOS1828 [pii] AID - 10.1111/j.1755-3768.2009.01828.x [doi] PST - ppublish SO - Acta Ophthalmol. 2011 Nov;89(7):670-5. doi: 10.1111/j.1755-3768.2009.01828.x. Epub 2010 Jan 8.