The Molecular Mechanism Of Retinal Degeneration And The Therapeutic Effects Of EGb761 On This Disease

Objective: To observe the influence of the photoreceptor apoptosis in the course of retinal degeneration to 17 region of visual cortex and its mechanism with the RCS rats as the animal model, and to observe the therapeutic effects of Ginaton (EGb761) on retinal dystrophy, and to explore the possible protective mechanism of EGb761. Methods: Choose RCS rats and SD rats at postnatal 9,15,20,25,30,35,40,60 days respectively. Observe the change of neurons of 17 region of visual cortex with Nissl staining and the expression of FasL and bcl-2 are detected by immunohistochemistry. A total of 48 male RCS rats were divided into control and EGb761 groups randomly. EGb761(100mg/kg/3d)was injected intraperitoneally in EGb761 group from postnatal 5 days. Similarly, saline was injected intraperitoneally in control group. The protective effects of EGb761 to retinal degeneration was assessed by the method of HE and TUNEL staining. The expression of FasL and bcl-2 were detected by immunohistochemistry.Results: (1) Nissl staining: Compared with SD rats, section areas of neurons of 17 region of visual cortex of RCS rats were smaller, and there were obvious difference at postnatal 20,25,30,35 days groups. The decreasing tendency of cell number of 17 region of visual cortex of RCS rats is lower than SD rats and there are more cells than SD rats. The difference has obvious significance at postnatal 30 and 35 days groups.(2) FasL and bcl-2 staining: Compared with SD rats, there are more FasL immunohistochemically positive cells in 17 region of visual cortex of RCS rats at postnatal 25,30,35,40 days groups and the optical density value(OD value) of the cells are higher at the four stage groups. There are more bcl-2 immunohistochemically positive cells and the OD value of these cells are higher at postnatal 30,35,40 days groups.( 3 ) HE staining: Compared with the control group, the inner nucleus layer(INL) of EGb761 group is thicker and the there are more cells in ganglion cell layer(GCL) and INL and more photoreceptors at postnatal 20 and 25 days groups. There is no obvious difference between the EGb761 and the control group after postnatal 30 days.(4) FasL and bcl-2 staining show that the EGb761 and control groups have similar expression pattern in FasL staining. From postnatal 15 to 25 days, there are less positive cells in the GCL and INL in EGb761 group than control group. Bcl-2 staining show that EGb761 group and control group are similar in expression pattern. TUNEL detectation show there are more positive cells in the outer nucleus layer(ONL) in EGb761 group than control group at postnatal 20 and 25 days groups. There is no obvious difference between EGb761 and control group at other stage groups. Conclusion: ( 1 ) EGb761 has therapeutic effect on the early stage of retinal degeneration. It might preserve more photoreceptors .(2)EGb761 might preserve degenerated neurons in the early stage by inhibiting the expression of FasL, but its protective effect may have no relationship with theexpression of bcl-2.( 3 ) In the early stage of retinal degeneration of RCS rats there are more cells in 17 region of visual cortex than control group, and the section area of the cells are bigger. The expression of FasL in early stage might have relationship with the differentiation and maturation of cells of visual cortex. The expression of FasL in visual cortex and in retina are in similar stages. It might be the adaptiveness of visual cortex to retinitis pigmentosa. The expression of bcl-2 in visual cortex may have relationship with the protective effects of itself.