Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.
Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, UK.
Int J Mol Sci. 2020 Aug 22;21(17):6055. doi: 10.3390/ijms21176055.
Retinitis pigmentosa (RP) is a generic term for a group of genetic diseases characterized by loss of rod and cone photoreceptor cells. Although the genetic causes of RP frequently only affect the rod photoreceptor cells, cone photoreceptors become stressed in the absence of rods and undergo a secondary degeneration. Changes in the gene expression profile of cone photoreceptor cells are likely to occur prior to observable physiological changes. To this end, we sought to achieve greater understanding of the changes in cone photoreceptor cells early in the degeneration process of the mouse model. To account for gene expression changes attributed to loss of cone photoreceptor cells, we normalized PCR in the remaining number of cones to a cone cell reporter (). Gene expression profiles of key components involved in the cone phototransduction cascade were correlated with tests of retinal cone function prior to cell loss. A significant downregulation of the photoreceptor transcription factor was observed, which preceded a significant downregulation in cone opsin transcripts that coincided with declining cone function. Our data add to the growing understanding of molecular changes that occur prior to cone dysfunction in a model of rod-cone dystrophy. It is of interest that gene supplementation of by adeno-associated viral vector delivery prior to cone cell loss did not prevent cone photoreceptor degeneration in this mouse model.
色素性视网膜炎（RP）是一组以杆状和锥状光感受器细胞丧失为特征的遗传疾病的统称。尽管 RP 的遗传原因通常仅影响杆状光感受器细胞，但在没有杆状细胞的情况下，锥状细胞会受到压力并发生继发性变性。锥状光感受器细胞的基因表达谱变化可能在可观察到的生理变化之前发生。为此，我们试图在小鼠模型的变性过程早期更深入地了解锥状光感受器细胞的变化。为了说明归因于锥状光感受器细胞丧失的基因表达变化，我们将剩余的锥状细胞数量的 PCR 归一化为锥状细胞报告基因 ()。与细胞丢失前的视网膜锥体细胞功能测试相关联，对参与锥状光转导级联的关键成分的基因表达谱进行了分析。观察到光感受器转录因子 的显著下调，这先于与锥状功能下降同时发生的锥状视蛋白转录本的显著下调。我们的数据增加了对模型中锥体细胞功能障碍之前发生的分子变化的理解，这与 rod-cone dystrophy。有趣的是，在锥状细胞丢失之前，通过腺相关病毒载体传递进行 的基因补充并没有阻止这种小鼠模型中锥状光感受器细胞的变性。
