Changes in neuronal response to ischemia in retinas with genetic alterations of somatostatin receptor expression
Author(s)
Date Issued
2007
Type
Article
Abstract
Ischemia is a primary cause of neuronal death in retinal diseases. The repertoire of expressed transmitter receptors would determine the neurons’ responses to ischemic damage, and peptidergic receptors may be involved. With a new in vitro model of the ischemic mouse retina, we investigated whether an altered expression of somatostatin receptors could modulate retinal responses to ischemia. We used retinas of somatostatin receptor 1 (sst1) knock out (KO) mice, where sst2 are over-expressed and over-functional, and of sst2 KO mice. TUNEL analysis of ischemic retinas showed a marked reduction of cell death in sst1 KO retinas, while there were no differences between wild-type (WT) and sst2 KO retinas. In addition, caspase-3 mRNA expression was also reduced in sst1 KO as compared to WT retinas. An immunohistochemical analysis demonstrated that different cell populations responded differently to the ischemic insult, and that the persistence of some immunohistochemical markers was greater in sst1 KO than in WT or in sst2 KO retinas. In particular, rod bipolar cell survival was markedly improved in sst1 KO retinas, while it was dramatically decreased in sst2 KO retinas. Furthermore, consistent with a role of glutamate excitotoxicity in ischemia-induced neuronal death, retinal glutamate release was observed to increase under ischemic conditions, but this increase was significantly reduced in sst1 KO retinas. These observations demonstrate that an increased presence of functional sst2 protects against retinal ischemia, thus implementing the background for the use of sst2 analogs in therapies of retinal diseases such as glaucoma or diabetic retinopathy.
Additional information
L'articolo è disponibile sul sito dell'editore http://onlinelibrary.wiley.com/
Citation
Catalani, E. et al. 2007. Changes in neuronal response to ischemia in retinas with genetic alterations of somatostatin receptor expression. "European Journal of Neuroscience" 25(5): 1447-1459
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Sponsor(s)
MiUR, PRIN, grant # 2005052312