Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia.
In mouse retinal explants, octreotide, a somatostatin [somatotropin release-inhibiting factor (SRIF)] receptor 2 (sst(2)) agonist, prevents the hypoxia-induced vascular endothelial growth factor upregulation. In mice with oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity, either sst(2) overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst(2) influences retinal degeneration in response to hypoxia in wild-type (WT), sst(1)- and sst(2)-knockout (KO) mice. In retinal explants, we determined the role of sst(2) on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst(1)-KO than in WT, but higher in sst(2)-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 sst(1)-KO retinas. To investigate the role of sst(2) 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 sst(1)-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst(1)-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst(1)-KO mice. Neither apoptotic signals nor ERG was affected by octreotide in sst(2)-KO mice. These results show that sst(2) may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst(2) pharmacology.
Dipartimento di Biologia, Università di Pisa, Via San Zeno, 31, Pisa, Italy.
Massimo
M
Dal Monte
Valentina
V
Latina
Elena
E
Cupisti
Paola
P
Bagnoli
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015282:Octreotide / Q000494:pharmacology; D010100:Oxygen; D017481:Receptors, Somatostatin / Q000502:physiology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000503:physiopathology*
D020533:Angiogenesis Inhibitors; D017481:Receptors, Somatostatin; C570769:somatostatin receptor 2, mouse; D053148:Caspase 3; D015282:Octreotide; D010100:Oxygen