PDF(Pubmed)
Abstract：
Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP\'s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.
摘要：
色素性视网膜炎（RP）是一种遗传性视网膜疾病，其中视锥介导的日光视力丧失。因为有超过100个疾病基因，我们的目标是以疾病基因不可知的方式保持视锥视力.以前我们显示过表达TXNIP，α-抑制蛋白，RP小鼠模型中延长的视锥视觉，使用AAV仅在锥体中表达。这里,我们在视网膜色素上皮（RPE）中表达了Txnip的不同等位基因，锥体的支撑层。我们的目标是了解更多的TXNIP的结构-功能关系为锥生存，以及确定视锥细胞存活的最佳细胞类型表达模式。发现TXNIP的C末端一半足以从细胞表面去除GLUT1，并提高了RP锥的存活率，当以RPE表示时，但不是在锥体。HSP90AB1是一种调节新陈代谢的TXNIP相互作用物，单独改善视锥细胞的存活率，并且与TXNIP结合使用时，视锥细胞的存活率是相加的。从这些和其他结果来看，TXNIP可能与RPE中的几种蛋白质相互作用，间接支持视锥细胞存活，这些相互作用中的一些与仅在视锥细胞中表达时导致视锥细胞存活的相互作用不同。
