Restoration of visual responses following transplantation of intact retinal sheets in rd mice
Restoration of visual responses following transplantation of intact retinal sheets in rd mice
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DOI：
10.1016/j.exer.2004.05.013
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发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Sadda, SR
中科院分区：
文献类型：
--
作者：
Arai, S;Thomas, BB;Sadda, SR
目的。目的：探讨胚胎视网膜片移植后小鼠视觉功能恢复的机制。21只出生后31-38天的小鼠（C3H/HeJ）单眼移植视网膜片(1)。0 × 0（.）4 mm)，从胚胎日(E) 17增强绿色荧光蛋白（eGFP）小鼠中获得。5只小鼠接受了不植入组织的假手术。移植后4至5周，记录了7只角膜和晶状体清晰的移植小鼠的7只眼睛和所有5只假手术小鼠的上丘（SC）对闪光的视觉反应。SC记录后，将眼睛去核，进行免疫组织化学处理，并用共聚焦显微镜检查。在7只眼睛中的3只（43%）中，在与移植体在宿主视网膜上的位置相对应的区域的SC中记录了阳性反应。未治疗的5周龄和9周龄rd/rd小鼠以及9周龄假手术小鼠的眼睛均无反应记录。相比之下，正常眼睛的整个SC都记录了视觉反应。3只有反应的移植小鼠的反应开始潜伏期与正常对照小鼠相似。移植物的组织似乎与电生理结果并不像预期的那样相关，因为有组织良好的叠层移植物的眼睛没有反应，而三个有光反应的眼睛有玫瑰花状或无组织的移植物。与未治疗的年龄匹配的rd/rd小鼠相比，移植后覆盖在宿主视网膜上的三只光反应眼均表现出更高水平的恢复免疫反应性。在rd小鼠中，SC视觉反应的恢复似乎并不依赖于组织良好的移植。光反应动物的宿主视网膜恢复染色增加，提示该移植模型中，宿主视锥细胞恢复可能是视力恢复的机制。(C) 2004 Elsevier Ltd.版权所有。
Purpose. To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration.Methods. Twenty-one postnatal day 31-38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1(.)0 x 0(.)4 mm) obtained from embryonic day (E) 17 enhanced-green-fluorescent protein (eGFP) mice. Five mice underwent sham surgery without insertion of tissue. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven transplanted mice that had clear corneas and lenses, and in all five sham surgery mice. Following the SC recording, the eyes were enucleated and processed for inummohistochemistry and examined using confocal microscopy.Results. In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5-week-old and 9-week-old rd/rd mice, and in the 9-week-old sham surgery mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies of the 3 transplanted mice with responses were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well-organized, laminated grafts showed no response whereas the three light-responsive eyes had rosetted or disorganized grafts. All three light-responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age-matched rd/rd mice.Conclusion. Restoration of the SC visual response does not appear to depend on a well-organized transplant in the rd mouse. Increased recoverin-staining in the host retina in light-responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model. (C) 2004 Elsevier Ltd. All rights reserved.