In a hindlimb ischemia model, NGF induced angiogenesis, suggesting that NGF upregulation is protective against both, neurodegeneration and vascular regression. Our previous data suggest that NGF treatment of diabetic rats prevents both, early neuroglial damage and the development of pericyte loss and vasoregression. Our present data indicate that NGF is only upregulated after the onset of vasoregression, and after substantial neuronal cell loss has occurred. In contrast, the two other neurotrophic factors studied, CNTF and FGF2, were upregulated prior to LDC000067 vasoregression and are found to be in close relationship with neurodegeneration. CNTF can delay photoreceptor degeneration in several models of genetic degeneration and ischemic injury. It is known that endogenous CNTF is upregulated in response to retinal injury, but the effect might be FIPI indirect rather than a direct effect, since the presence of CNTF-receptors on photoreceptors has not been unequivocally demonstrated. CNTF belongs to the CNTF/LIF group of cytokines. These have been extensively studied for their role in photoreceptor development. However, much less is known about the impact on vascular function. Recently, Kubota et al have demonstrated that LIF is involved in regulating microvessel density by regulating VEGF expression in mice. LIF-/- mice had a denser capillary network with sustained tip cell activity, and despite resistance to hyperoxic vasoregression, they developed more neovascular tufts. These data suggest that there may be a link between the vasoregressive phenotype and increased expression of the CNTF/LIF family of cytokines in the retina of TGR. CNTF expression parallels that of FGF2 in our TGR model. FGF2 knockout mice develop photoreceptor degeneration suggesting that FGF2 plays an important role in photoreceptor development and survival. Multiple degenerative and injurious retina models yield upregulation of FGF2 suggesting the pleiotropic and essential role for FGF2 in survival of retinal cells.The lack of functional FGF2 could be a factor that causes the impaired protection of the diabetic retina from progressive vasoregression during the non-proliferative phase.