Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia

Abstract

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.

Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy

“…However, the inhibitory effect of AKBA on the neovascular response does not seem to result in improved visual function, as indicated by the ERG data which are similar in vehicle-and in AKBA-treated OIR retinas. This is different from the results obtained in previous studies, where other substances with documented anti-angiogenic effects in OIR retinas were also observed to rescue, at least in part, the electroretinographic responses (Dal Monte et al, 2012a;Martini et al, 2011). However, there is also evidence indicating that treatments preventing pathological angiogenesis may not necessarily prevent retinal dysfunction (Hatzopoulos et al, 2014).…”

“…6CeE, the amplitude of a-and b-waves, as well as SOPs, at light intensity of 1 log cd-s m À2 are reported. As previously described Vessey et al, 2011;Dal Monte et al, 2012a), OIR mice displayed significantly reduced a-and b-wave amplitudes, as well as SOPs, compared with control mice (Fig. 5CeE).…”

“…The electrophysiological signals were recorded as previously described Dal Monte et al, 2012a). Briefly, mice were dark adapted overnight and anesthetized by intraperitoneal injection of Avertin.…”

β3-Adrenoceptors: a drug target in ophthalmology?

“…The present study by Dal Monte et al provides possible pathways by which β 3 -adrenoceptor agonists/antagonists may modulate VEGF release through NO in vascular endothelial cells and surrounding cells, including neuroglial cells (Dal Monte et al 2013). This work expands on previous work of the same group on hypoxia in the retina (Dal Monte et al 2012a) and other tissues .…”

Anti‐inflammatory and retinal protective effects of capsaicin on ischaemia‐induced injuries through the release of endogenous somatostatin

“…Our results indicated that pretreatment with the selective SST‐depleting agent cysteamine or using an SST receptor antagonist, such as c‐SOM, to some extent, reversed the effects of CAP, illustrating that the endogenous SST released into circulation played effective roles in anti‐inflammation and neuroprotection. Many studies have established that exogenous SST or synthetic analogues exert anti‐inflammatory and/or neuroprotective effects . Szolcsanyi et al.…”