Choi Elliot H, Daruwalla Anahita, Suh Susie, Leinonen Henri, Palczewski Krzysztof
Department of Ophthalmology, Gavin Herbert Eye Institute, Center for Translational Vision Research, University of California, Irvine, CA, USA; Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA; Departments of Physiology and Biophysics, and Chemistry, University of California, Irvine, CA, USA.
J Lipid Res. 2021;62:100040. doi: 10.1194/jlr.TR120000850. Epub 2021 Feb 6.
Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans-cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)-retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.
在光子能量的驱动下，视杆和视锥光感受器细胞中的视觉色素将11-顺式视黄醛异构化为全反式构型。这种光化学反应启动了信号转导通路，最终导致视觉信号传递至大脑，并使视蛋白对进一步的光刺激不敏感。为了使眼睛恢复光敏感性，视蛋白需要重新与11-顺式视黄醛结合。这种反-顺式的逆向转化是通过一系列构成类视黄醇（视觉）循环的酶促反应实现的。尽管经典的类视黄醇循环对视觉至关重要这一点很明显，但11-顺式视黄醛再生的辅助途径的存在多年来一直存在争议。视网膜色素上皮（RPE）-视网膜G蛋白偶联受体（RGR）先前已被鉴定为一种与在无脊椎动物中发现的视紫红质同源的哺乳动物视黄醛光异构酶。研究人员现在使用药理学、遗传学和生物化学方法，确定了RGR在11-顺式视黄醛再生中的生理相关性。RGR在RPE和Müller胶质细胞中的光异构酶活性解释了眼睛在日光下如何保持反应能力。在这篇综述中，我们将重点关注眼睛中的类视黄醇代谢以及由RGR介导的视觉发色团再生。
