Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa
Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa
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DOI：
10.1167/iovs.02-0615
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
McCall, MA
中科院分区：
文献类型：
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作者：
Sagdullaev, BT;Aramant, RB;McCall, MA
目的.绘制转基因S334 terline-3大鼠上级丘（SC）视网膜驱动活动的时空下降图，转基因S334 terline-3大鼠表达突变的视紫红质，导致感光细胞变性。目的：探讨将胚胎视网膜片移植到这些大鼠的视网膜下腔是否能恢复SC中的视觉活动。向眼睛提供视觉刺激，并记录28 - 288日龄未给药S334 terline-3大鼠SC的反应。这些数据被用来绘制暗点发展图。将来自胚胎第19天大鼠的完整视网膜片移植到21至28天龄的S334 ter-line-3大鼠的视网膜下腔中。手术后78至163天，在移植和假手术对照大鼠的SC中绘制对视网膜刺激的反应。检查所有组中视网膜的形态。未处理大鼠的感光细胞损失与SC中视觉活动的下降相匹配。在第28天，代表中央视网膜的SC区域中存在暗点，并且在第63天，它已经扩大到覆盖整个视网膜表示。64%的视网膜移植大鼠诱发了视觉反应。这些视网膜驱动的反应局限于SC的一个小的连续区域，该区域代表了放置移植物的视网膜部分。在移植受者的SC中，在该区域以外的SC中不存在视觉反应，而在未治疗和假手术对照大鼠的整个SC中也不存在视觉反应。在此RP模型中，胚胎视网膜片移植诱导SC中视觉活动的恢复。这种功能恢复的机制仍有待解决，但这些结果表明，移植应进一步探讨作为RP的治疗。
PURPOSE. To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334terline-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can recover visual activity in the SC.METHODS. A visual stimulus was presented to the eye, and responses were recorded across the SC of untreated S334terline-3 rats aged 28 to 288 days. These data were used to draw a map of the developing scotoma. Intact retinal sheets from embryonic day 19 rats were transplanted into the subretinal space of S334ter-line-3 rats between 21 and 28 days of age. Responses to retinal stimulation were mapped in the SC of transplanted and sham control rats 78 to 163 days after surgery. The morphology of the retinas in all groups was examined.RESULTS. Photoreceptor cell loss in untreated rats matched the decline in visual activity in the SC. At 28 days, there was a scotoma in the area of the SC that represents the central retina and, by 63 days, it had enlarged to cover the entire retinal representation. Visual responses were evoked in 64% of rats with retinal transplants. These retinally driven responses were confined to a small, contiguous region of the SC that represents the sector of the retina where the transplant was placed. Visual responses were absent in the SC outside this area in transplant recipients and throughout the SC of untreated and sham control rats.CONCLUSIONS. Transplantation of fetal retinal sheets induced recovery of visual activity in the SC in this model of RP. The mechanisms underlying this functional recovery remain to be resolved, but these results suggest that transplantation should be further explored as a therapy for RP.