Department of Pharmacology, Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 ; Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio 44106.
Department of Pharmacology, Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Annu Rev Vis Sci. 2016 Oct;2:197-234. doi: 10.1146/annurev-vision-111815-114407. Epub 2016 Jul 18.
Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions.
近年来，对哺乳动物视网膜视黄醛循环的分子理解的进展源于艰苦的生化重建研究，这些研究得到了具有已知遗传缺陷的天然或工程动物模型的支持，以及对具有特定遗传致盲疾病的人类的研究。结构和膜生物学已被用于检测关键的视网膜酶和蛋白质及其底物和配体，并将它们置于细胞环境中。这些研究得到了分析化学方法的补充，这些方法通过其光谱特征识别小分子，通常与评估动物视网膜疾病模型结合使用。正是在这种背景下，确定了纠正遗传缺陷或环境损伤的合理治疗干预措施。因此，目前大多数被接受的视黄醛循环调节剂已经在视网膜变性的动物模型中显示出有希望的结果。这些令人鼓舞的迹象表明，一些人类致盲疾病可以通过药物干预来缓解。
