On the other hand, we observed that the expression of a series of inflammation-related genes was altered by ethanol treatment and Smad7 deletion. Chemokines and a number of proinflammatory cytokines were all elevated by either ethanol treatment or Smad7 deletion. Furthermore, ethanol treatment and Smad7 deletion had a synergistic effect to induce expression of F4/ 80, IFN-c and IL-6, indicating that these factors may underlie the aggravated liver dysfunction in Smad7-deleted mice upon ethanol administration. Combining these results, we propose that the alteration of ethanol metabolism, lipogenesis and inflammatory response caused by Smad7 deletion may act together to contribute to severe alcoholic liver injury and steatosis in Smad7-deleted mice. In this regard, our model of liver-specific deletion of Smad7 can serve as a useful tool to comprehend the biological function of endogenous Smad7 in the liver as well as in liver diseases. Pathogenic events in diabetic retinopathy include capillary basement membrane thickening, loss of microvascular intramural pericytes and leaky dilation. At more advanced stages, capillary occlusion induces retinal ischemia and subsequent retinovitreal neovascularization causing bleeding and traction retinal detachments. Since its discovery in ocular fluids from patients with proliferative diabetic retinopathy, VEGF has been recognized as a major pro angiogenic factor produced in response to hyperglycaemia and ischemia. Even though few animal models reproduce one or more of the DR lesions with unquestionable validity, non-diabetic animal models have been exploited to study retinal neovascularization pathogenesis. The retinopathy of prematurity model is commonly used to study ischemic-related retinal diseases. The angiogenic effects of VEGF have also been analyzed in transgenic mice models of ocular neovascularizations or using viral VEGF gene transfer. Whilst VEGF blockade has been demonstrated to efficiently reduce neovascularization progression and leakage in age-related macular degeneration, its exact place in the management of DR Sorafenib remains to be clarified. Intravitreal anti- VEGFs do improve vitrectomy outcome in cases of severe PDR but should be administered shortly before surgery to avoid traction retinal detachments, and may potentially Pazopanib aggravate retinal ischemia. The effectiveness of anti VEGF therapies in patients with diabetic macular edema remains disputable and suggests that other hypoxia-induced molecular factors may be involved such as PDGF, IGF-1, HGF, bFGF/FGF- 2. Among them, placental growth factor found at high levels in the vitreous and the retina of diabetic patients may have particular interest.