title: VIP, PACAP-38, BDNF and ADNP in NMDA-induced excitotoxicity in the rat retina.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Teuchner
authors.forename: Andreas
authors.initials: A
authors.lastname: Dimmer
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
authors.forename: Albert
authors.initials: A
authors.lastname: Amberger
authors.forename: Reiner
authors.initials: R
authors.lastname: Fischer-Colbrie
authors.forename: Jozsef
authors.initials: J
authors.lastname: Nemeth
authors.forename: James A
authors.initials: JA
authors.lastname: Waschek
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kieselbach
authors.forename: Martina
authors.initials: M
authors.lastname: Kralinger
authors.forename: Eduard
authors.initials: E
authors.lastname: Schmid
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Bechrakis
authors.forename: Josef
authors.initials: J
authors.lastname: Troger
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005444:Flunarizine / Q000008:administration & dosage; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009842:Oligopeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009842:Oligopeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C410622:activity-dependent neurotrophic factor; D014660:Vasoactive Intestinal Peptide; D016202:N-Methylaspartate; D005444:Flunarizine