Abstract：
The retina undergoes compensatory changes in response to progressive photoreceptor loss/dysfunction; however, studies of inherited retinal diseases (IRDs) often lack a temporal connection between gene expression and visual function. Here, we used three mouse models of IRD - Cnga3-/-, Pde6ccpfl1, and Rd1 - to investigate over time the effect of photoreceptor degeneration, particularly cones, on visual function and gene expression. Changes to gene expression include increases in cell survival and cell death genes in Pde6ccpfl1 before significant cell loss, as well as an increase in cone-specific genes in the Rd1 at the peak of rod death. We show that Cnga3-/- and Pde6ccpfl1 mice maintained photopic visual acuity via optomotor responses, despite no recordable cone electroretinogram (ERG), while functional measures and photoreceptors loss were correlated in Rd1 mice. There were also significant changes to oscillatory potentials (OPs) in Cnga3-/- and Pde6ccpfl1, implying an effect on inner retinal cells as a result of cone degeneration. These results indicate a potentially malleable retinal environment following cone degeneration; however, further investigation is needed to elucidate how these changes compensate for the loss of cone function.
摘要：
视网膜发生代偿性变化，以应对进行性光感受器丧失/功能障碍；然而，遗传性视网膜疾病（IRD）的研究通常缺乏基因表达与视觉功能之间的时间联系。这里,我们使用了三种IRD-Cnga3-/-小鼠模型，Pde6ccpfl1和Rd1-随着时间的推移，研究光感受器变性的影响，尤其是锥体，视觉功能和基因表达。基因表达的变化包括在显著细胞丢失之前Pde6ccpfl1中细胞存活和细胞死亡基因的增加，以及杆死亡高峰时Rd1中视锥特异性基因的增加。我们表明，Cnga3-/-和Pde6ccpfl1小鼠通过视电机反应保持明视视力，尽管没有可记录的锥形视网膜电图（ERG），而Rd1小鼠的功能测量和光感受器丧失相关。Cnga3-/-和Pde6ccpfl1中的振荡电位（OP）也有显着变化，这意味着视锥变性会对内部视网膜细胞产生影响。这些结果表明视锥变性后可能有延展性的视网膜环境；然而，需要进一步的研究来阐明这些变化是如何补偿锥功能的损失的。
