Pigment Epithelium-derived Factor Is Helpful In Treatment Of A Murine Model Of Oxygen-induced Ischemia Retinopathy

PrefaceAberrant blood vessel growth in retina that underlied the pathology of prolif-erative diabetic retinopathy and retinopathy of prematurity ( ROP) was the result of the ischemia - derived disruption of the normally antiangiogenic environment of the retina. Pigment epithelium -derived factor (PEDF) was a potent inhibitor of angiogenesis found naturally in the normal eye. In this study, we showed that PEDF could inhibit such aberrant blood vessel growth in a murine model of ischemia - induced retinopathy and PEDF may be beneficial in the treatment of a variety of retinal vasculopathies.Materials and MethodsWe needed 110 neonates Wister rats. They were put into an oxygen supply glass box and fed with their mother from postnatal day (P)7 to P12 and returned to room air, during this period the concentration of oxygen was measured 3 times a day to keep at about 75%. At P17 mice were killed and their eyes were enucleated for quantitation of retinal neovascularization.Air control group were maintained in room air throughout the experiment without any administration. Air PEDF group received an intravitreal injection of PEDF at P12,P14,P16 and were maintained in room air throughout the experiment . Hyperxia control group received nothing and were maintained in hyperxia condition. Hyperxia PBS group and hyperxia PEDF group received an intravitreal injection of PEDF and vehicle respectively at P12,P14,P16 and both weremaintained in hperxia condition. Ten eyes from each group were observed the vessels of retina. Four eyes form each group were detected their vessels newly generated.Results1. The concentration of oxygen Oxygen concentration was (75 ± 2) %.2. Vessels of the retinaIn air control group the main vessels of retina were thick, there could be seen retinal capillaries around optic papilla and the retinal capillaries were mature. In air PEDF group the growth of vessels was identical with blank control group. In Hyperxia control group, the main vessels of retina were thin, retinal capillaries hyperplasied and many leakage points could be found. The main vessels of retina and'the development of retinal capillaries were approximately identical in the hyperxia control group and hyperxia PBS group. In hyperxia PEDF group , the main vessels of retina thinned and neovascularization was reduced obviously compared with hyperxia control group.3. Pathologic changes of retinaHyperxia PEDF group & newly generated capillaries obviously reduced compared with hyperxia control group.CommentsRetinal neovascularization underlied the pathology of proliferative diabetic retinopathy and retinopathy of prematurity. The pathological growth of new blood vessels in the eye and the leaks and tissue disruption it causes were responsible for most cases of vision loss. In the study, we used a highly reproducible mouse model of ischemia - induced retinal neovascularization.The major natural inhibitor in the vitreous and cornea of the eye was pigment epithelium - derived factor ( PEDF) , a protein produced by retinal pig-ment epithelial cells and found at high concentrations within the retina as well as in the vitreous, where it was responsible for the antiangiogenic activity of this fluid. PEDF was a member of serine protease inhibitor family, although it did not have protease inhibitory activity. PEDF has been demonstrated to protect photoreceptors from degeneration and to inhibited neovascularization.In hyperxia PEDF group, the consistent suppression of retinal neovascularization by PEDF across all animals offered independent confirmation of PEDF s inhibitory action on retinal neovascularization. In addition, the finding that PEDF given intravitreally was effective may have important clinical implications, because an intravitreal mode of treatment may help to minimize any possible side effects associated with systemic PEDF administration.But PEDF played a complicated function on it's inhibitory activity which need further investigation.ConclusionPEDF was helpful in treatment of murine model of oxygen - induced ische-mic retinopathy and there emerge a new view that PEDF may be helpful to other neovascular retinopathy.