“…In fact, hyperglycemia induces, through various routes, an enhanced generation of diacylglycerol, [10,13] the physiological activator of PKC, that at the retinal level seems to predominantly stimulate the beta isoform of the kinase [15], although, as already mentioned, other PKC isoenzymes are also activated [16,17]. The crucial involvement of PKCβ is further emphasized, on the one hand, by a A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 13 dramatic increase in the angiogenic response to retinal ischemia in transgenic mice overexpressing PKCβ and, on the other hand, by a significant decrease in retinal neovascularization in PKCβ null mice [38]. Moreover, besides the retina, it has been observed that the lack of PKCβ can protect against diabetic-induced dysfunctions and augment VEGF expression in other tissues affected by this pathology [39].…”