In diabetic retinopathy, the arteries in the retina weaken and leak, causing retinal ischaemia. New vessels develop to improve oxygenation but these haemorrhage easily and many patients eventually lose their eyesight. Paradoxically, endothelial cell apoptosis is increased in diabetic retinopathy, even though the endothelial survival factor VEGF is upregulated. On p. 243, Azza El-Remessy et al. suggest that the high glucose concentrations present in diabetic individuals block the pro-survival effects of VEGF by simultaneously decreasing the activity of Akt1, a kinase acting in an anti-apoptotic pathway downstream of VEGF, and increasing the activity of pro-apoptotic p38 MAP kinase. They show that apoptosis in retinal endothelial cells in vitro increases after treatment with glucose or peroxynitrite, a product of glucose-induced oxidative stress. These treatments decrease Akt1 phosphorylation through tyrosine nitration of the PI 3-kinase that phosphorylates Akt1 and increase phosphorylation of p38 MAP kinase. The authors conclude that upregulation of the Akt1 anti-apoptotic signalling pathway through blockade of tyrosine nitration could provide a way to control early diabetic retinopathy.