Researches On The Change Of Visual Pathway In Ad Model Mice

Objective: To compare the pathological change of the retina,opticnerve and visual cortex between APP/PS1double transgenic mice and wildtype mice.Method: Retina were removed from APP/PS1double transgenic miceand wild-type controls in different ages. Immunohistochemical stainingwas performed to observe the expression of APP and Aβ in the retina andvisual cortex of both groups of mice; Immunofluorescent stainingcombined with retinal stretched preparation was undertaken to observe themorphological and density changes of astrocytes in the retina of bothgroups; Electron microscopy was performed to observe the pathologicalchange of the retina, optic nerve and visual cortex of both groups.Computerimage analysis system was used to analyze the data.Result: APP positive cells were observed in the retina of both APP/PS1double transgenic mice and wild-type mice, while a significant i ncrease of APP expression was seen in the APP/PS1double transgenic mice, when compared with that of wild-type controls（P=0.018<0.05, t=3.232; P=0.001<0.05, t=5.797). Aβ deposition was hardly observed in the retina of wild-type mice; however, its depositions were significantly increased in the retina of APP/PS1double transgenic micewith an age-dependant manner; Aβ deposition was hardly observed in the visual cortex of wild-type mice, while a small amount of senile plques were observed in the3months APP/PS1double transgenicmice（P=0.001<0.05,t=10.156）,and a mass of senile plques were observed in the12months APP/PS1double transgenic mice（P=0.002<0.05,t=10.633）. A significant increase of numbers and density of astrocytes were observed in the retina of APP/PS1double transgenic mice,as compared with wild type mouse. The optic nerve ultrastructure ofAPP/PS1double transgenic mice shows: a small amount of axons with demyelinating lesions at3months, and widespread demyelinatinglesions at12months. Visual cortex ultrastructure of APP/PS1doubletransgenic mice shows: neurons were shrinkage, dim, chromatin condensed and margination at3months APP/PS1double transgenic mice,12months APP/PS1double transgenic mice more serious and appeared many vacuoles and lipofuscins. Retinal ultrastructure of APP/PS1double transgenic mice shows: the structure of the membrane plate fuzzy, and the space were widen. Ganglion cell morphological disorder, protuberant swelling significantly.Conclusion: Aβ deposition is increased with age in the retina ofAPP/PS1double transgenic mice and accompanys with reactiveastrogliosis，which maybe lead to retinal membrane plate and ganglion cellslesions. In the visual cortex of APP/PS1double transgenic mice, thenumber of SP increases with the age, and closely associates with neuronalapoptosis. Optic nerve axons demyelinating obvious in APP/PS1doubletransgenic mice, but the mechanism is unknown. Objective:To examine the pathological changes of retina inchronicbrain ischemia model mice.Method:C57mice were used to establish chronic brain ischemiamodel. According to different ischemia time, divided into ischemia120dayand180day group, sham-operation as control group. Use immunohistoche-mical staining and immunofluorescent staining combined with retinalstretched preparation to observe the distribution and expression of Aβ、GFAP、AQP4、HIF-1α、VEGF、Bax、Bcl-2、Caspase-9in the mice retinaat different ischemic time period.Result: The expression level of Aβ、GFAP、AQP4、HIF-1α、VEGFand Caspase-9were very low or not expression in the sham operatedgroup,while in the operated group，the expression were significantlyincreased. The expression of Bcl-2was significantly increased in controlgroup than surgery group, and the expression of Bax was significantlyincreased in the surgery group than control group. Immunofluorescentstaining combined with retinal stretched preparation shows astrocytes lostnormal structure, the morphological were abnormal, the number were increased, cell axon became longer,and some cells were stacked.Conclusion: The expression of Aβ、GFAP、AQP4、HIF-1α、VEGF andCaspase-9were increased in the retina of chronic cerebral ischemia modelmice. The expression of Bcl-2was increased in control group than surgerygroup, and the expression of Bax was increased in the surgery group thancontrol group.The present study indicated that all of them are involved inthe pathological changes of the retinal ischemia injury process and plays animportant role in the mechanism of retinal ischemia injury.