The Study On The Inhibitive Effects Of Genistein On The Ocular Neovascularization

(Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical Universit 210029)Neovascular diseases of the retina are one of the major causes of blindness in the world. Vision loss in pathological conditions such as diabetic retinopathy, retinopathy of prematurity, ischemic retinal-vein occlusion, and age-related macular degeneration is characterized by the extensive proliferation of new blood vessels in the retina. Hypoxia is the common stimulus of these pathologic states associated with uncontrolled angiogenesis. Recently, it is widely accepted by the researchers that a specific cytokine, vascular endothelial growth factor ( VEGF ) plays a primary role in angiogenic processes~[1-3]. It is an endothelial cell-specific mitogen which is stimulated by hypoxia and required for proliferation in some tumors. In ocular tissues, studies have demonstrated that VEGF production is increased by hypoxia in retinal cells, retinal pericytes. VEGF is expressed in the retina prior to the onset of neovascularization in a mouse model of proliferative retinopathy. Finally, there is a high correlation between VEGF expression and the retinal neovascularization associated with a variety of ocular diseases. Cultured human retinal cells such as pigmentepithelial cells and pericytes secrete VEGF and increase VEGF gene and protein expression in response to hypoxia. Zhang et al ~[4,5] reported that hypoxia could induce the proliferation of RPE cells and the up-regulation of the expression of VEGF. Furthermorem, bFGF has close relation with hypoxia and can stimulate the growth of endothelium cells, which plays a great role in the course of hypoxia-induced ocular neovascularization which coorperates with VEGF and EGF. Research had found that there were bFGF and its receptors on the surface of RPE cells. The researchers also found that bFGF accelerated neovascularization, rehabilitation of damnification, the development of embryo, the function of differentiated nerve,and the degeneration of the nerve tissue~[7-9]. The over expression of bFGF can induce the tumor ~[10,11], uncontrolling neovascularization and the proliferation of cells. Inhibition of the produce of VEGF, bFGF in RPE cells can reduce neovascularization, than provide a new way for the therapy of Neovascular diseases of the retina. On the other side, reactive species were concerned with both the damage and singal transfer. In the different cells, Oxidative stress regulate many physiological and biochemical raaction with the participation of reactive species, such as the proliferation, differentiation, apopotiat of cells, and the neovascularization caused by it.Current therapies such as panretinal photocoagulation and cryotherapy, are only partially effective and are destructive to the retina. Alternative, nondestructive modes of therapy could be of benefit to patients with these blindness-causing diseases. We found genistein, a naturally occurring isoflavoneisolated from soybean~[12], provide a viable therapy for diseases characterized by retinal neovascularization . Recently it has been reported that genistein could inhibit neovascularization in a surgical model of choriocapillaris atrophy by surgical debriding the retinal pigment epithelium (RPE) in rabbits and in a model of retina ischemia in mice~[13]. Our previous~[14] study found that genistein could concentration-dependently inhibit VEGF protein expression induced by CoCl2 and hypoxia in cultured rabbit retinal pigment epithelium(RPE) cells. Furthermore, genistein markedly inhibited the number of nuclei protruding above the inner limiting membrane and the VEGF and HIF-1 α expression under relative hypoxia condition. Moreover, it has less toxicity than conventional chemical anti angiogenesis agents.Here we have a study on the inhibitive effect of genistein on the oclur neovascularization: (1)the establish of the model of retinal neovascularization in habbits and the inhibitive effect of genistein on the retinal neovascularization in habbits;(2) observed the time course changes of VEGF expression induced by hy...