Little C W, Cox C, Wyatt J, del Cerro C, del Cerro M
Department of Neurobiology, University of Rochester School of Medicine, New York 14642, USA.
Exp Neurol. 1998 Jan;149(1):151-60. doi: 10.1006/exnr.1997.6642.
This study uses a water maze paradigm as a tool to assess posttransplantation changes in behavior associated with a visual stimulus. A set of dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received subretinal injections of vehicle. All animals were immunosuppressed. At 2 months posttransplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the tank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during 10 consecutive trials. The swimming paths and times for all rats were recorded and statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologic analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. The water escape data indicated the differences between the sham and experimental groups changed significantly over time (P = 0.0017). Over time, the transplanted animals learned to use light as a clue (P < 0.0001), whereas the sham animals did not (P = 0.73). Transplanted eyes had a significantly greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and compared with either region of sham-injected eyes (P = 0.0023). Statistical analyses demonstrated a functional advantage for visually guided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at 2 months after transplantation.
本研究采用水迷宫范式作为工具，以评估与视觉刺激相关的移植后行为变化。一组营养不良的RCS大鼠在赤道上半球的视网膜下间隙接受双侧新鲜分离的人胎儿视网膜色素上皮（RPE）细胞注射。五只年龄匹配的对照营养不良RCS大鼠接受视网膜下注射赋形剂。所有动物均接受免疫抑制。移植后2个月，每只大鼠在水迷宫装置中进行测试。大鼠利用随机位于水箱边缘的单个光源来定位直接位于光源前方的水下平台。每只大鼠在连续10次试验中被计时并录像。记录所有大鼠的游泳路径和时间并进行统计分析。水迷宫试验后，将眼睛包埋进行组织学分析，包括对预定义视网膜区域的光感受器细胞进行定量评估。水迷宫数据表明，假手术组和实验组之间的差异随时间显著变化（P = 0.0017）。随着时间的推移，移植动物学会将光作为线索（P < 0.0001），而假手术动物则没有（P = 0.73）。移植眼在上方移植区域的光感受器平均数量明显多于同一只眼的下方区域，且与假注射眼的任何一个区域相比均有显著差异（P = 0.0023）。统计分析表明，移植人胎儿RPE细胞的RCS大鼠在视觉引导行为方面具有功能优势，且在移植后2个月有统计学显著的光感受器细胞拯救效应。
