首页> 外文期刊>The Journal of Physiology >Retinol dehydrogenase 8 and ATP-binding cassette transporter 4 modulate dark adaptation of M-cones in mammalian retina
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Retinol dehydrogenase 8 and ATP-binding cassette transporter 4 modulate dark adaptation of M-cones in mammalian retina

机译:视黄醇脱氢酶8和ATP结合盒转运蛋白4调节哺乳动物视网膜中M-锥体的暗适应。

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Rapid recycling of visual chromophore and regeneration of the visual pigment are critical for the continuous function of mammalian cone photoreceptors in daylight vision. However, the molecular mechanisms modulating the supply of visual chromophore to cones have remained unclear. Here we explored the roles of two chromophore-binding proteins, retinol dehydrogenase 8 (RDH8) and photoreceptor-specific ATP-binding cassette transporter 4 (ABCA4), in dark adaptation of mammalian cones. We report that young adult RDH8/ABCA4-deficient mice have normal M-cone morphology but reduced visual acuity and photoresponse amplitudes. Notably, the deletion of RDH8 and ABCA4 suppressed the dark adaptation of M-cones driven by both the intraretinal visual cycle and the retinal pigmented epithelium (RPE) visual cycle. This delay can be caused by two separate mechanisms: direct involvement of RDH8 and ABCA4 in cone chromophore processing, and an indirect effect from the delayed recycling of chromophore by the RPE due to its slow release from RDH8/ABCA4-deficient rods. Intriguingly, our data suggest that RDH8 could also contribute to the oxidation of cis-retinoids in cones, a key reaction of the retina visual cycle. Finally, we dissected the roles of rod photoreceptors and RPE for dark adaptation of M-cones. We found that rods suppress, whereas RPE promotes, cone dark adaptation. Thus, therapeutic approaches targeting the RPE visual cycle could have adverse effects on the function of cones, making the evaluation of residual cone function a critical test for regimens targeting the RPE.
机译:视觉生色团的快速回收和视觉色素的再生对于哺乳动物视锥光感受器在日光下的连续功能至关重要。但是,尚不清楚调节视色团向视锥细胞供应的分子机制。在这里,我们探讨了两种发色团结合蛋白,视黄醇脱氢酶8(RDH8)和感光受体特异性ATP结合盒转运蛋白4(ABCA4)在哺乳动物视锥细胞的暗适应中的作用。我们报告说,年轻的成年RDH8 / ABCA4缺陷小鼠具有正常的M锥形态,但降低了视敏度和光响应幅度。值得注意的是,RDH8和ABCA4的缺失抑制了视网膜内视觉周期和视网膜色素上皮(RPE)视觉周期驱动的M-锥体的暗适应。这种延迟可能是由两种独立的机制引起的:RDH8和ABCA4直接参与锥发色团的处理,以及由于RPE从RDH8 / ABCA4缺陷棒中缓慢释放而导致发色团延迟回收,从而产生间接影响。有趣的是,我们的数据表明RDH8还可促进视锥细胞中顺式维甲酸的氧化,这是视网膜视觉周期的关键反应。最后,我们剖析了杆状感光体和RPE对M锥的暗适应的作用。我们发现棒抑制,而RPE促进,锥暗适应。因此,针对RPE视觉周期的治疗方法可能会对视锥细胞功能产生不利影响,从而使残余视锥细胞功能的评估成为针对RPE的治疗方案的关键测试。

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