Green E S, Menz M D, LaVail M M, Flannery J G
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
Invest Ophthalmol Vis Sci. 2000 May;41(6):1546-53.
To determine the extent to which rhodopsin mis-sorting and constitutive activation of the phototransduction cascade contribute to retinal degeneration in a transgenic rat model of retinitis pigmentosa.
Retinas from transgenic rats expressing truncated rhodopsin (Ser334ter) were examined by light and electron microscopic immunocytochemistry at several time points. Retinal degeneration in transgenic rats raised in darkness was evaluated by quantification of outer nuclear layer thickness and by electroretinography.
Mutant rhodopsin was found at inappropriately high levels in the plasma membrane and cytoplasm of Ser334ter rat photoreceptors. When the cell death rate was high this mis-sorting was severe, but mis-sorting attenuated greatly at later stages of degeneration, as the cell death rate decreased. The distributions of two other outer segment proteins (the cGMP-gated channel and peripherin) were examined and found to be sorted normally within the photoreceptors of these rats. Raising Ser334ter transgenic rats in darkness resulted in minimal rescue from retinal degeneration.
Because dark rearing Ser334ter rats results in little rescue, it is concluded that constitutive activation of the phototransduction cascade does not contribute significantly to photoreceptor cell death in this rat model. The nature of the rhodopsin sorting defect and the correlation between the severity of mis-sorting and rate of cell death indicate that truncated rhodopsin may cause apoptosis by interfering with normal cellular machinery in the post-Golgi transport pathway or in the plasma membrane.
在视网膜色素变性转基因大鼠模型中，确定视紫红质错误分选和光转导级联的组成性激活对视网膜变性的影响程度。
在多个时间点，通过光镜和电镜免疫细胞化学检查表达截短视紫红质（Ser334ter）的转基因大鼠的视网膜。通过定量外核层厚度和视网膜电图评估在黑暗中饲养的转基因大鼠的视网膜变性。
在Ser334ter大鼠光感受器的质膜和细胞质中发现突变型视紫红质水平异常高。当细胞死亡率高时，这种错误分选很严重，但随着细胞死亡率降低，在变性后期错误分选大大减弱。检查了另外两种外段蛋白（cGMP门控通道和外周蛋白）的分布，发现它们在这些大鼠的光感受器内分选正常。在黑暗中饲养Ser334ter转基因大鼠对视网膜变性的挽救作用极小。
由于在黑暗中饲养Ser334ter大鼠几乎没有挽救作用，得出的结论是，在该大鼠模型中，光转导级联的组成性激活对光感受器细胞死亡没有显著影响。视紫红质分选缺陷的性质以及错误分选的严重程度与细胞死亡率之间的相关性表明，截短的视紫红质可能通过干扰高尔基体后运输途径或质膜中的正常细胞机制而导致细胞凋亡。
