Perusek Lindsay, Maeda Akiko, Maeda Tadao
Department of Ophthalmology and Visual Sciences, School of Medicine, Case Western Reserve University, Adelbert Road 2085, Cleveland, OH, 44106, USA.
Methods Mol Biol. 2015;1271:345-62. doi: 10.1007/978-1-4939-2330-4_22.
The perception of light begins when photons reach retinal tissue located at the back of the eye and photoisomerize the visual chromophore 11-cis-retinal to all-trans-retinal within photoreceptor cells. Isomerization of 11-cis-retinal activates the protein rhodopsin located in photoreceptor outer segments, thereby inducing a phototransduction cascade leading to visual perception. To maintain vision, 11-cis-retinal is regenerated in the retinal pigmented epithelium (RPE) via the visual cycle and delivered back to the photoreceptor cells where it may again bind to rhodopsin. Distinct pathological mechanisms have been observed to contribute to inherited retinal degenerative diseases including severe delay in 11-cis-retinal regeneration and delayed clearance of all-trans-retinal, which leads to the accumulation of harmful retinoid by-products. In the last decade, our group has conducted several proof-of-concept (POC) studies with retinoid derivatives aimed at developing treatments for retinal degenerative diseases caused by an impaired visual cycle. Here, we will introduce experimental procedures, which have been developed for POC studies involving retinoid biology.
当光子到达位于眼球后部的视网膜组织,并使光感受器细胞内的视觉发色团11-顺式视黄醛光异构化为全反式视黄醛时,光感知过程便开始了。11-顺式视黄醛的异构化激活了位于光感受器外段的视紫红质蛋白,从而引发一个光转导级联反应,最终导致视觉感知。为了维持视觉,11-顺式视黄醛通过视觉循环在视网膜色素上皮(RPE)中再生,并被输送回光感受器细胞,在那里它可能再次与视紫红质结合。已观察到不同的病理机制会导致遗传性视网膜退行性疾病,包括11-顺式视黄醛再生严重延迟和全反式视黄醛清除延迟,这会导致有害类视黄醇副产物的积累。在过去十年中,我们团队进行了多项使用类视黄醇衍生物的概念验证(POC)研究,旨在开发针对因视觉循环受损而导致的视网膜退行性疾病的治疗方法。在此,我们将介绍为涉及类视黄醇生物学的POC研究而开发的实验程序。