Cellular properties of intrinsically photosensitive retinal ganglion cells during postnatal development

Jasmine A Lucas,Tiffany M Schmidt

doi:10.1186/s13064-019-0132-2

Abstract

BackgroundMelanopsin-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.MethodsWe 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.ResultsOur 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.ConclusionsThis 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.

Highlights

Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells respond directly to light and have been shown to mediate a broad variety of visual behaviors in adult animals. Intrinsically photosensitive retinal ganglion cells (ipRGC) are 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
Morphological properties of ipRGC subtypes during development In order to assess the morphological and physiological properties of ipRGC subtypes during development, we first needed to confirm that we could reliably identify each subtype at early postnatal stages using criteria available to differentiate the adult subtypes
IpRGC subtypes are identifiable in early postnatal development via dendritic stratification and SMI-32 immunohistochemistry As with adult animals, we found that we were able to use dendritic stratification and SMI-32 to differentiate between M1, M2, and M4 ipRGCs. ipRGC stratification could be clearly identified at P6, and all of the ipRGCs in this dataset were clearly monostratified, even at P6

Summary

Introduction

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 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. Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a class of non-canonical, ganglion cell photoreceptors These cells influence a variety of visual behaviors including contrast sensitivity [1], circadian photoentrainment [2,3,4], sleep [5, 6], and even mood [7, 8]. IpRGCs have been categorized based on their adult characteristics, they are light sensitive from embryonic stages [10,11,12] and begin to exhibit diverse light response properties at early postnatal stages [13, 14] These unique photoreceptors are light sensitive long before the rest of the retinal circuitry is able to functionally relay rod/cone signals around ~P12 when the eyes open [15, 16]. Light and melanopsin can even drive a light avoidance behavior in neonatal mice as young as 6 days old [19]

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Conclusion