Involvement of Beclin-1 in axonal protection by short-term hyperglycemia against TNF-induced optic nerve damage

Beclin-1 serves a pivotal role in autophagosome formation. A previous study demonstrated that streptozotocin-induced hyperglycemia (HG) ameliorates axonal loss induced by tumor necrosis factor (TNF) with upregulation of autophagy in rats. The aim of present study was to examine whether Beclin-1 is involved in this autophagy machinery. Immunoblot analysis of optic nerves demonstrated that HG upregulated Beclin-1 protein expression when compared with normoglycemia (NG). Intravitreal administration of TNF did not alter the optic nerve Beclin-1 expression in NG nor in HG. Beclin-1 immunoreactivity was revealed to be mainly in astrocytes in optic nerves; however, it was also observed in the neurofilaments of the HG group. Morphometric analysis revealed that HG appeared to have substantial ameliorative effects on axon loss and this ameliorative effect was partially prevented by Beclin-1 small interfering RNA. These results indicated that Beclin-1 may exist in neurons and glia in optic nerves and increased Beclin-1 expression may be at least partially associated with axonal protection by HG.