Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Departments of Clinical Genetics and Ophthalmology, University of Amsterdam, Amsterdam UMC, AMC, Amsterdam, The Netherlands.
J Biol Rhythms. 2022 Oct;37(5):567-574. doi: 10.1177/07487304221112845. Epub 2022 Jul 31.
Daily biological rhythms are fundamental to retinal physiology and visual function. They are generated by a local circadian clock composed of a network of cell type/layer-specific, coupled oscillators. Animal models of retinal degeneration have been instrumental in characterizing the anatomical organization of the retinal clock. However, it is still unclear, among the multiple cell-types composing the retina, which ones are essential for proper circadian function. In this study, we used a previously well-characterized mouse model for autosomal dominant retinitis pigmentosa to examine the relationship between rod degeneration and the retinal circadian clock. This model carries the P23H mutation in rhodopsin, which induces mild rod degeneration in heterozygous and rapid loss of photoreceptors in homozygous genotypes. By measuring PER2::LUC bioluminescence rhythms, we show that the retinal clock in heterozygous mice displays circadian rhythms with significantly increased robustness and amplitude. By treating retinal explants with L-α aminoadipic acid, we further provide evidence that this enhanced rhythmicity might involve activation of Müller glial cells.
昼夜节律是视网膜生理学和视觉功能的基础。它们是由一个由细胞类型/层特异性耦合振荡器组成的局部生物钟产生的。视网膜变性的动物模型在描述视网膜生物钟的解剖组织方面发挥了重要作用。然而，在构成视网膜的多种细胞类型中，哪些对正常的昼夜节律功能至关重要，目前仍不清楚。在这项研究中，我们使用了一种先前经过充分表征的常染色体显性遗传性视网膜色素变性的小鼠模型，研究了 rod 变性与视网膜昼夜节律钟之间的关系。该模型携带视紫红质中的 P23H 突变，该突变导致杂合子中 rod 轻度变性，纯合子中光感受器迅速丧失。通过测量 PER2::LUC 生物发光节律，我们表明杂合子小鼠的视网膜钟具有显著增强的稳健性和振幅的昼夜节律。通过用 L-α 氨基酸己二酸处理视网膜外植体，我们进一步提供了证据表明这种增强的节律性可能涉及 Muller 胶质细胞的激活。
