Neuronal injury plays a major role in diabetic retinopathy (DR). Our hypothesis was that the balance between neuronal death and survival may depend on a similar equilibrium between apoptosis and autophagy and that a neuroprotectant may act by influencing this equilibrium. Ex vivo mouse retinal explants were treated with high glucose (HG) for 10 days and the somatostatin analog octreotide (OCT) was used as a neuroprotectant. Chloroquine (CQ) was used as an autophagy inhibitor. Apoptotic and autophagic markers were evaluated using western blot and immunohistochemistry. HG-treated explants displayed a significant increase of apoptosis paralleled by a significant decrease of the autophagic flux, which was likely to be due to increased activity of the autophagy regulator mTOR (mammalian target of rapamycin). Treatment with OCT rescued HG-treated retinal explants from apoptosis and determined an increase of autophagic activity with concomitant mTOR inhibition. Blocking the autophagic flux with CQ completely abolished the anti-apoptotic effect of OCT. Immunohistochemical observations showed that OCT-induced autophagy is localized to populations of bipolar and amacrine cells and to ganglion cells. These observations revealed the antithetic role of apoptosis and autophagy, highlighting their equilibrium from which neuronal survival is likely to depend. These data suggest the crucial role covered by autophagy, which could be considered as a molecular target for DR neuroprotective treatment strategies.
Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy / R. Amato, E. Catalani, M. Dal Monte, M. Cammalleri, I. Di Renzo, C. Perrotta, D. Cervia, G. Casini. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 128(2018 Feb), pp. 167-178.
|Titolo:||Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy|
|Parole Chiave:||amacrine cells; apoptosis; autophagic flux; bipolar cells; ganglion cells; somatostatin; pharmacology|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||feb-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.phrs.2017.09.022|
|Appare nelle tipologie:||01 - Articolo su periodico|