In mouse retinal explants, octreotide, a somatostatin (SRIF) receptor 2 (sst2) agonist, prevents the hypoxia-induced vascular endothelial growth factor upregulation. In mice with oxygen induced retinopathy (OIR), a model of retinopathy of prematurity, either sst2 overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst2 influences retinal degeneration in response to hypoxia in wild type (WT), sst1- and sst2- knockout (KO) mice. In retinal explants, we determined the role of sst2 on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst1-KO than in WT, but higher in sst2-KO than in WT retinas. In all strains, a comparable increase in caspase-3 activity and the Bax/Bcl-2 ratio was observed after hypoxia. The hypoxia-induced increase in apoptotic signals was recovered by octreotide in both WT and sst1-KO retinas. To investigate the role of sst2 on retinal function, we recorded electroretinogram (ERG) in response to light flashes in OIR mice. ERG responses did not differ between WT and KO mice with the exception of oscillatory potentials (OPs), which in sst1-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst1-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst1-KO mice. Neither apoptotic signals nor ERG were affected by octreotide in sst2-KO mice. These results show that sst2 may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst2 pharmacology.
|Autori:||DAL MONTE M; LATINA V; CUPISTI E; BAGNOLI P|
|Titolo:||Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia|
|Anno del prodotto:||2012|
|Digital Object Identifier (DOI):||10.1007/s00210-012-0735-1|
|Appare nelle tipologie:||1.1 Articolo in rivista|