Pasireotide (SOM230) protects the retina in animal models of ischemia induced retinopathies
| Autor: | Ioannis Charalampopoulos, Niki Mastrodimou, Despina Kokona, Iosif Pediaditakis, Kyriaki Thermos, H.A. Schmid |
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| Rok vydání: | 2012 |
| Předmět: |
Apoptosis
AMPA receptor Nitric Oxide Synthase Type I Pharmacology Biology Neuroprotection Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound Retinal Diseases In vivo medicine In Situ Nick-End Labeling Animals Receptors Somatostatin Fluorescent Antibody Technique Indirect Protein kinase C Protein Kinase C Retina Antagonist Retinal Flow Cytometry Sensory Systems Rats Ophthalmology Disease Models Animal medicine.anatomical_structure Amacrine Cells Neuroprotective Agents chemistry Reperfusion Injury Somatostatin Neuroscience Oligopeptides Ex vivo |
| Zdroj: | Experimental eye research. 103 |
| ISSN: | 1096-0007 |
| Popis: | The neuropeptide somatostatin and selective analogs for the sst(2/5) receptor subtypes provided neuroprotection against retinal chemical ischemia ex vivo and AMPA [(RS)-α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide] induced retinal toxicity in vivo, when employed in micromolar concentrations (Mastrodimou et al., 2005; Kiagiadaki and Thermos, 2008). The aim of the present study was to investigate the neuroprotective properties of a new metabolically stable agent pasireotide (SOM230) in the above mentioned retinal models of ischemia. Adult Sprague Dawley (250-350 g) rats were employed. For the ex vivo experiments, retinal eye cups were incubated with PBS or the chemical ischemia mixture [iodoacetic acid (5 mM)/sodium cyanide (25 mM)] in the absence or presence of SOM230 (10(-7)-10(-5) M) alone or in the presence of the sst(2) antagonist CYN-154806 (10(-7) or 10(-5) M). In the in vivo model, the animals received intravitreally: PBS (50 mM), AMPA (42 nmol/eye) or AMPA (42 nmol) in combination with SOM230 (10(-7)-10(-5) M). Immunohistochemistry studies using antisera against bNOS, a marker for brain/neuronal NOS containing amacrine cells, protein kinase C (PKC) a marker for rod bipolar cells, and TUNEL studies in conjunction with FACS analysis were employed to examine retinal cell loss and protection. Chemical ischemia led to a loss of bNOS and PKC immunoreactivity which was reversed by SOM230. Partial and full protection of bNOS and PKC immunoreactive neurons, respectively, was observed even at the low concentration of 10(-7) M. The neuroprotective actions of SOM230 (10(-7) or 10(-5) M) were reversed by CYN-154806 (10(-7) or 10(-5) M, respectively). Similarly, SOM230 (10(-7), 10(-6), 10(-5) M) provided neuroprotection in the in vivo model. The dose of 10(-7) M prevented the loss of the bNOS cells and provided almost full protection. These data were substantiated by TUNEL staining and fluorescence-activated cell sorting (FACS) analysis. SOM230 appears very efficacious in its neuroprotective properties in both models of retinal ischemia affording neuroprotection at the concentration or dose of 100 nM. These data suggest that SOM230 might represent a useful pharmacological compound for the treatment of retinal disease. |
| Databáze: | OpenAIRE |
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