Polgenix, Cleveland, Ohio, USA.
Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA.
Nat Med. 2014 Jul;20(7):785-9. doi: 10.1038/nm.3590. Epub 2014 Jun 22.
Two-photon excitation microscopy can image retinal molecular processes in vivo. Intrinsically fluorescent retinyl esters in subcellular structures called retinosomes are an integral part of the visual chromophore regeneration pathway. Fluorescent condensation products of all-trans-retinal accumulate in the eye with age and are also associated with age-related macular degeneration (AMD). Here, we report repetitive, dynamic imaging of these compounds in live mice through the pupil of the eye. By leveraging advanced adaptive optics, we developed a data acquisition algorithm that permitted the identification of retinosomes and condensation products in the retinal pigment epithelium by their characteristic localization, spectral properties and absence in genetically modified or drug-treated mice. This imaging approach has the potential to detect early molecular changes in retinoid metabolism that trigger light- and AMD-induced retinal defects and to assess the effectiveness of treatments for these conditions.
双光子激发显微镜可以在体成像视网膜的分子过程。在称为视脂体的亚细胞结构中，内源性荧光视黄酯是视觉色素再生途径的一个组成部分。全反式视黄醛的荧光缩合物随年龄的增长在眼睛中积累，并且也与年龄相关性黄斑变性（AMD）有关。在这里，我们报告了通过眼睛的瞳孔对活体小鼠中这些化合物的重复，动态成像。通过利用先进的自适应光学，我们开发了一种数据采集算法，该算法可以通过其特征定位、光谱特性以及在基因修饰或药物处理的小鼠中不存在来识别视网膜色素上皮中的视脂体和缩合物。这种成像方法有可能检测到触发光和 AMD 诱导的视网膜缺陷的视黄醇代谢的早期分子变化，并评估这些疾病的治疗效果。
