PDF(Pubmed)
Abstract：
Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.
摘要：
细胞视黄醛结合蛋白（CRALBP）支持11-顺式视黄醛的产生及其向光感受器的递送。在视网膜色素上皮（RPE）和Müller胶质细胞（MG）中发现，但这两个细胞池的相对功能重要性存在争议。这里,我们报告了RPE和MG特异性CRALBP基因敲除(KO)小鼠,并检查了它们的光感受器和视觉循环功能。RPE-KO小鼠的大量视觉发色团再生比对照组慢15倍，考虑到它们延迟的杆暗适应和对视网膜光毒性的保护，而MG-KO小鼠具有正常的视觉生色团再生和视网膜光损伤易感性。锥形色素再生在RPE-KO小鼠中明显受损，但在MG-KO小鼠中受到轻度影响，揭示了视锥光感受器对基于RPE的视觉周期的出乎意料的强烈依赖。这些数据揭示了RPE-CRALBP在支持视杆和视锥功能中的主导作用，并突出了RPE细胞靶向对CRALBP基因治疗的重要性。
