However, we also did not find a downregulation of VEGF as has been observed in some models of neurodegeneration, in which VEGF deficiency can impair neuronal survival. Neurotrophic factors expressed in neuroglial cells of the retina, such FGF2, CNTF, and NGF,SCH727965 may play an important role in retinal neurodegeneration. NGF injection rescues photoreceptor degeneration in the RCS rat model of retinitis pigmentosa, involving secondary effects by other neurotrophins such as FGF2 and VEGF. NGF also inhibits retinal degeneration in the C3H mouse. 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 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 indirect rather than a direct effect,SCH772984 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.