کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4011283 1602619 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Pasireotide (SOM230) protects the retina in animal models of ischemia induced retinopathies
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
Pasireotide (SOM230) protects the retina in animal models of ischemia induced retinopathies
چکیده انگلیسی

The neuropeptide somatostatin and selective analogs for the sst2/5 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 sst2 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.


► SOM230, a sst1,2,3,5 agonist, protects retinal neurons in models of retinopathy.
► It decreased retinal apoptotic cell death as shown by TUNEL FACS analysis.
► Its pharmacological profile renders it appropriate as a retinal therapeutic.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 103, October 2012, Pages 90–98
نویسندگان
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