Secretoneurin and the tachykinins substance P and neurokinin-A/B in NMDA-induced excitotoxicity in the rat retina.
In a recent investigation using the NMDA-excitotoxicity model in the rat retina, we found that, whereas, following intravitreal injection of NMDA, a time-dependent decrease of the levels of a neuropeptide, namely vasoactive intestinal polypeptide (VIP), was fully counteracted by topical treatment with flunarizine eye drops, the levels of pituitary adenylate-cyclase activating peptide-38 (PACAP-38), another neuropeptide, remained unchanged. The aim of the present study was to find out if NMDA causes reduction in the levels of other neuropeptides such as secretoneurin (SN), neurokinin-A/B (NKA/NKB) and substance P (SP), and if so, whether flunarizine has the ability to counteract this effect or prevent such reduction. The reduction of the levels of SN and NKA/NKB 14 days after intravitreal injection of 2 μl of 100 nmol NMDA into one eye was more pronounced than after 7 days; topical flunarizine had a slight counteracting effect, but could not prevent the decrease in the levels of these peptides. Reduction in SP levels after 28 and 56 days was fully counteracted by flunarizine. By enabling a pronounced influx of Ca²+ ions into peptide-expressing cells, NMDA leads to cell death. Since each of these peptides exerts neuroprotective properties in the central nervous system, the drop in their levels caused by acute insult (e.g. NMDA excitotoxicity) or chronic insult (e.g. glaucoma) may cause a breakdown of endogenous neuroprotection in the retina given that these peptides feature neuroprotective properties in the retina as well.
Department of Ophthalmology, Medical University Innsbruck, Innsbruck, Austria.
Barbara
B
Teuchner
Andreas
A
Dimmer
Josef
J
Troger
Reiner
R
Fischer-Colbrie
Eduard
E
Schmid
Gerhard
G
Kieselbach
Hermann
H
Dietrich
Nikolaos
N
Bechrakis
D000818:Animals; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D015288:Neurokinin A / Q000378:metabolism*; D015287:Neurokinin B / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism*; D053381:Secretogranin II / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
D009479:Neuropeptides; D053381:Secretogranin II; C081159:secretoneurin; D013373:Substance P; D016202:N-Methylaspartate; D015288:Neurokinin A; D015287:Neurokinin B