视网膜色素上皮特异性65kDa蛋白功能减退对视杆和视锥光感受器的影响

The Consequences of Hypomorphic RPE65 for Rod and Cone Photoreceptors.

作者信息

Samardzija Marijana, Barben Maya, Geiger Philipp, Grimm Christian

机构信息

Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, Wagistr. 14, 8952, Schlieren, Switzerland.

出版信息

Adv Exp Med Biol. 2016;854:341-6. doi: 10.1007/978-3-319-17121-0_45.

DOI:10.1007/978-3-319-17121-0_45

PMID:26427430

Abstract

RPE65 is essential for both rod- and cone-mediated vision. So far, more than 120 disease-associated mutations have been identified in the human RPE65 gene. Differential clinical manifestations suggested that some patients suffer from null mutations while others retain residual RPE65 activity and some useful vision. To understand the mechanism of retinal degeneration or dysfunction caused by such hypomorphic RPE65 alleles, we generated an Rpe65 (R91W) knock-in mouse (R91W) that expresses a mutant RPE65 protein with reduced function. Data obtained suggested that the R91W mouse is highly suitable to study the impact of RPE65 insufficiency on rod pathophysiology. To study the impact on cones, we combined the R91W with the Nrl (-/-) mouse that develops an all-cone retina. Here we summarize the consequences of hypomorphic RPE65 function (reduced 11-cis-retinal synthesis) for rod and cone pathophysiology.

摘要

RPE65对于视杆细胞和视锥细胞介导的视觉都至关重要。到目前为止，已在人类RPE65基因中鉴定出120多种与疾病相关的突变。不同的临床表现表明，一些患者存在无效突变，而另一些患者则保留了残余的RPE65活性和一些有用的视力。为了了解由这种低表达RPE65等位基因引起的视网膜变性或功能障碍的机制，我们构建了一种Rpe65（R91W）基因敲入小鼠（R91W），该小鼠表达功能降低的突变型RPE65蛋白。获得的数据表明，R91W小鼠非常适合研究RPE65功能不足对视杆细胞病理生理学的影响。为了研究对视锥细胞的影响，我们将R91W与发育成全视锥细胞视网膜的Nrl（-/-）小鼠进行了杂交。在此，我们总结了低表达RPE65功能（11-顺式视黄醛合成减少）对视杆细胞和视锥细胞病理生理学的影响。