VIP,PACAP‐38, BDNF and ADNP in NMDA‐induced excitotoxicity in the rat retina |
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| Authors: | Barbara Teuchner Andreas Dimmer Christian Humpel Albert Amberger Reiner Fischer‐Colbrie Jozsef Nemeth James A. Waschek Gerhard Kieselbach Martina Kralinger Eduard Schmid Nikolaos Bechrakis Josef Troger |
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| Affiliation: | 1. Department of Ophthalmology, Medical University of Innsbruck, Innsbruck, Austria;2. Laboratory of Psychiatry, Medical University of Innsbruck, Innsbruck, Austria;3. Tyrolean Cancer Research Institute, Medical University of Innsbruck, Innsbruck, Austria;4. Department of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria;5. Department of Pharmacology and Pharmacotherapy, University of Debrecen, Hungary;6. Mental Retardation Research Center, Semel Institute for Neuroscience, The David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA |
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| Abstract: | 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. |
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| Keywords: | ADNP BDNF NMDA PACAP‐30 retina VIP |
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