Department of Neurobiology, Northwestern University, Evanston, IL, USA.
Neural Dev. 2019 Aug 30;14(1):8. doi: 10.1186/s13064-019-0132-2.
Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light and have been shown to mediate a broad variety of visual behaviors in adult animals. ipRGCs are also the first light sensitive cells in the developing retina, and have been implicated in a number of retinal developmental processes such as pruning of retinal vasculature and refinement of retinofugal projections. However, little is currently known about the properties of the six ipRGC subtypes during development, and how these cells act to influence retinal development. We therefore sought to characterize the structure, physiology, and birthdate of the most abundant ipRGC subtypes, M1, M2, and M4, at discrete postnatal developmental timepoints.
We utilized whole cell patch clamp to measure the electrophysiological and morphological properties of ipRGC subtypes through postnatal development. We also used EdU labeling to determine the embryonic timepoints at which ipRGC subtypes terminally differentiate.
Our data show that ipRGC subtypes are distinguishable from each other early in postnatal development. Additionally, we find that while ipRGC subtypes terminally differentiate at similar embryonic stages, the subtypes reach adult-like morphology and physiology at different developmental timepoints.
This work provides a broad assessment of ipRGC morphological and physiological properties during the postnatal stages at which they are most influential in modulating retinal development, and lays the groundwork for further understanding of the specific role of each ipRGC subtype in influencing retinal and visual system development.
表达黑视蛋白的光敏感视网膜神经节细胞（ipRGC）直接对光起反应，并已被证明在成年动物中介导广泛的各种视觉行为。ipRGC 也是发育中视网膜中的第一光敏感细胞，并且已经涉及到许多视网膜发育过程，如视网膜血管系统的修剪和视网膜投射的细化。然而，目前对于发育过程中六种 ipRGC 亚型的特性以及这些细胞如何影响视网膜发育知之甚少。因此，我们试图在离散的出生后发育时间点表征最丰富的 ipRGC 亚型 M1、M2 和 M4 的结构、生理学和出生日期。
我们利用全细胞膜片钳技术测量 ipRGC 亚型在出生后的发育过程中的电生理和形态特性。我们还使用 EdU 标记来确定 ipRGC 亚型终末分化的胚胎时间点。
我们的数据表明，ipRGC 亚型在出生后的早期就可以彼此区分开来。此外，我们发现虽然 ipRGC 亚型在相似的胚胎阶段终末分化，但它们达到成人样形态和生理学的时间点不同。
这项工作提供了在最能调节视网膜发育的出生后阶段对 ipRGC 形态和生理学特性的广泛评估，并为进一步了解每个 ipRGC 亚型在影响视网膜和视觉系统发育中的具体作用奠定了基础。
