IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.07-1644 on April 4, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:3080-3089.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1644
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.07-1644v1
49/7/3080    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kiagiadaki, F.
Right arrow Articles by Thermos, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kiagiadaki, F.
Right arrow Articles by Thermos, K.

Effect of Intravitreal Administration of Somatostatin and sst2 Analogs on AMPA-Induced Neurotoxicity in Rat Retina

Foteini Kiagiadaki and Kyriaki Thermos

From the Laboratory of Pharmacology, Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.

PURPOSE. The aim of the present study was to use an in vivo model of retinal excitotoxicity to investigate the neuroprotective effect of somatostatin (SRIF)-ergic agents.

METHODS. Adult Sprague–Dawley rats (weight range, 250–300 g) intravitreally received (RS)-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA; 21, 42, 84 nmol/eye) or PBS (50 mM). Time-dependent responses were examined in animals that received AMPA (42 nmol/eye). Animals received AMPA (42 nmol) alone or in combination with SRIF (10–5, 10–4 M) or the sst-selective ligands lanreotide (sst2,10–5,10–4 M), L-779976 (sst2,10–6,10–5, 10–4 M), L-797591 (sst1,10–4 M), and L-803087 (sst4,10–4 M). Immunohistochemistry and TUNEL studies were used to examine retinal cell loss and protection. Immunochemistry, Western blot analysis, and radioimmunoassay assessed the viability of sst2A receptors and SRIF levels, respectively, in control and AMPA-treated tissue.

RESULTS. AMPA (42 nmol) treatment resulted in total and major loss of ChAT and bNOS immunoreactivity, respectively, 24 hours after its administration. This loss was sustained up to 30 days for ChAT- and 8 days for bNOS-expressing amacrine cells. SRIF and the sst2 receptors were not affected by AMPA. SRIF and the sst2 analogs protected the retina from the AMPA insult in a dose-dependent manner, whereas activation of the sst1 and sst4 subtypes had no effect. TUNEL staining confirmed AMPA-induced retinal ischemia and L-779976 neuroprotection.

CONCLUSIONS. These results demonstrate for the first time that SRIF and the sst2 analogs, administered intravitreally, protect the retina from excitotoxicity. Further studies are essential to ascertain the therapeutic relevance of these results.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Association for Research in Vision and Ophthalmology