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视网膜色素上皮(RPE)移植后RCS营养不良大鼠视蛋白和S抗原基因表达的维持

Maintenance of opsin and S-antigen gene expression in RCS dystrophic rats following RPE transplantation.

作者信息

Gaur V, Agarwal N, Li L, Turner J E

机构信息

Department of Neurobiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.

出版信息

Exp Eye Res. 1992 Jan;54(1):91-101. doi: 10.1016/0014-4835(92)90073-2.

Abstract

The effects of retinal pigment epithelium (RPE) transplantation in rescuing photoreceptor cells (PRC) were studied in RCS rats bearing the rdy mutation. RPE preparations from Long-Evans rats were transplanted into the subretinal space of post-natal (P) 17-19-day-old RCS rats. Age-matched RCS animals in the control group received injections of the transplantation vehicle buffer alone. The animals were killed at various post-natal ages after RPE transplantation. Immunocytochemical studies using antibodies to opsin and S-antigen indicated intact photoreceptor cells in the transplanted retinas. In contrast age-matched sham-injected animals did not show any rescue of photoreceptor cells at P90. Single RPE transplantation of 60,000 cells in each eye resulted in restoration of near normal mRNA levels for opsin, and S-antigen proteins. Comparisons of mRNA levels of two visual proteins using cDNA probes demonstrated a therapeutic effect of RPE transplantation in preventing a progressive decline in mRNA levels due to retinal degeneration. In contrast, P109 sham-injected controls showed no detectable mRNA levels for these proteins. In vitro protein synthesis in RPE-transplanted retinas implied further competence of these retinas. These data suggest that RPE transplantation not only rescues photoreceptors from degeneration, but more importantly, it allows normal transcription and translation in these cells rendering them capable of participating in the visual and signal transduction cascade.

摘要

在携带rdy突变的RCS大鼠中,研究了视网膜色素上皮(RPE)移植对挽救光感受器细胞(PRC)的作用。将来自Long-Evans大鼠的RPE制剂移植到出生后(P)17 - 19日龄的RCS大鼠的视网膜下间隙。对照组中年龄匹配的RCS动物仅接受移植载体缓冲液注射。在RPE移植后的不同出生后年龄处死动物。使用视蛋白和S抗原抗体进行的免疫细胞化学研究表明,移植的视网膜中有完整的光感受器细胞。相比之下,年龄匹配的假注射动物在P90时未显示光感受器细胞的任何挽救情况。每只眼睛单次移植60,000个RPE细胞可使视蛋白和S抗原蛋白的mRNA水平恢复到接近正常水平。使用cDNA探针比较两种视觉蛋白的mRNA水平表明,RPE移植具有治疗作用,可防止因视网膜变性导致的mRNA水平逐渐下降。相比之下(此处原文有误,根据前文应是“相比之下”),P109假注射对照组中这些蛋白的mRNA水平检测不到。RPE移植视网膜中的体外蛋白质合成意味着这些视网膜具有进一步的功能。这些数据表明,RPE移植不仅能使光感受器免于退化,更重要的是,它能使这些细胞进行正常的转录和翻译,使其能够参与视觉和信号转导级联反应。

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