The retinal pigment epithelium of the vertebrate eyes acquires vitamin A from circulating retinol binding protein for chromophore biosynthesis. The chromophore covalently links with an opsin protein in the adjacent photoreceptors of the retina to form the bipartite visual pigment complexes. We here analyzed visual pigment biosynthesis in mice deficient for the retinol-binding protein receptor STRA6. We observed that chromophore content was decreased throughout the life cycle of these animals, indicating that lipoprotein-dependent delivery pathways for the vitamin cannot substitute for STRA6. Changes in the expression of photoreceptor marker genes, including a downregulation of the genes encoding rod and cone opsins, paralleled the decrease in ocular retinoid concentration in STRA6-deficient mice. Despite this adaptation, cone photoreceptors displayed absent or mislocalized opsins at all ages examined. Rod photoreceptors entrapped the available chromophore but exhibited significant amounts of chromophore-free opsins in the dark-adapted stage. Treatment of mice with pharmacological doses of vitamin A ameliorated the rod phenotype but did not restore visual pigment synthesis in cone photoreceptors of STRA6-deficient mice. The imbalance between chromophore and opsin concentrations of rod and cone photoreceptors was associated with an unfavorable retinal physiology, including diminished electrical responses of photoreceptors to light, and retinal degeneration during aging. Together, our study demonstrates that STRA6 is critical to adjust the stoichiometry of chromophore and opsins in rod and cone photoreceptors and to prevent pathologies associated with ocular vitamin A deprivation.

中文翻译：

---

维生素 A 转运蛋白 STRA6 在视觉色素合成和回收中调节生色团和视蛋白的化学计量

脊椎动物眼睛的视网膜色素上皮从循环的视黄醇结合蛋白中获取维生素 A，用于生色团的生物合成。发色团与视网膜相邻光感受器中的视蛋白共价连接，形成二分视觉色素复合物。我们在这里分析了缺乏视黄醇结合蛋白受体 STRA6 的小鼠的视觉色素生物合成。我们观察到，在这些动物的整个生命周期中，发色团含量都在下降，这表明维生素的脂蛋白依赖性递送途径不能替代 STRA6。光感受器标记基因表达的变化，包括编码视杆蛋白和视锥蛋白的基因的下调，与 STRA6 缺陷小鼠的眼类视黄醇浓度降低平行。尽管有这种适应，在所检查的所有年龄段，视锥细胞都显示出缺失或错误定位的视蛋白。杆状光感受器捕获了可用的生色团，但在暗适应阶段表现出大量的无生色团视蛋白。用药理学剂量的维生素 A 治疗小鼠改善了视杆表型，但没有恢复 STRA6 缺陷小鼠视锥细胞的视觉色素合成。视杆和视锥细胞的生色团和视蛋白浓度之间的不平衡与不利的视网膜生理有关，包括光感受器对光的电反应减弱以及衰老过程中的视网膜退化。一起，