IGF 1 can mediate VEGF expression by mechanisms independent in addition to dependent of HIF 1, including tension and cytokine induced production. Furthermore, transgenic mice overexpressing IGF 1 in the retina develop vascular alterations that resemble human diabetic retinopathy. Both placenta growth factor e3 ubiquitin and VEGF increase Akt phosphorylation and activate downstream substrates. Fresh blockade of PI3K service and transmission by over-expression of adenovirus mediated phosphatases that disrupt Akt phosphorylation also disrupt angiogenesis. Therefore, several growth facets that have shown a role in the development of the characteristic of human proliferative diabetic retinopathy are from the PI3K/ Akt/mTOR pathway for the regulation of these expression and activity. The mTOR path in addition has been implicated in other pathobiology of the retina. The dedifferentiation of RPE and subsequent photoreceptor degeneration is associated with mTOR service. The inhibition of mTOR pathway can suppress RPE dedifferentiation together with availability of photoreceptor Urogenital pelvic malignancy functionality in rats. The recognition that mTOR is involved in hypoxia and that oxygen levels manage mTOR function assisted vasoproliferative answers suggests a somewhat novel downstream useful link between hypoxia and mitogenic signaling involved in proliferation of vascular cells. These collective findings suggest that PI3K/Akt/mTOR pathway inhibition would be suited to handle the advanced proliferative stages of diabetic retinopathy where hypoxia driven vasoproliferative mechanisms predominate in adding to the vasculopathy. 7. PI3K/Akt/mTOR Inhibitors as Potential Therapeutics The inhibition of the PI3K/Akt/mTOR pathway is a nice-looking therapeutic target for diabetic retinopathy because functionally it’s a convergent MAP kinase inhibitor pathway for an assortment of growth facets, pro inflammatory mediators, and downstream substrates which can be regulators of cellular survival techniques necessary to the initiation and progression of the angiogenic cascade. Novel results concerning the regulation of VEGF expression in the retina of animals claim that hyperglycemia induces VEGF protein expression via eukaryotic initiation factor 4E and its binding proteins. Mice null for these proteins did not display increases in VEGF protein started by hyperglycemia. The 4E BP1 proteins and eIF4E are downstream effectors of the regulatory mTOR complex 1, thereby, implicating a functional role of this pathway inside the pathobiology of diabetic retinopathy. Several inhibitors of the PI3K superfamily have been described. The pharmacologic agents LY294002 and wortmannin both target the p110 catalytic subunit of PI3K.