bioRxiv2019
Sensory stimulation plays a critical role in the maturation of sensory organs and systems. For example, when deprived of light before birth, foetal mouse pups in utero exhibit altered ocular vascular development. Normal vascular development depends on light excitation of melanopsin, a non-rod, non-cone photopigment that is expressed in a subset of ganglion cells (mRGCs) in the retina. However, there is no direct evidence that mRGCs in foetal eyes are light-responsive. Very little is known about how light absorption leads to excitation in these foetal neurons. Using mRGC-specific expression of the calcium indicators GCaMP3 and GCaMP6, we report that foetal mouse mRGCs respond to light as early as 4 days before birth. Further, two distinct Gq/11-G protein family antagonists, FR9000359 and YM-254890, abolish these light responses. TTX, a blocker of voltage-activated sodium channels, reversibly represses light responses, and FPL6417 and L-cis-diltiazem, which modify L-type calcium channels, respectively increase and reduce light responses. Electrophysiological patch pipette recordings show that embryonic mRGCs respond to light of intensity as low as 2.9 x 1012 photons/cm2/s. The present findings demonstrate a heretofore unproven but postulated light sensitivity in the retinas of foetal mice and identify the transduction pathways involved. Surprisingly, mRGCs do not function as completely independent photoreceptors but are electrotonically coupled with other mRGCs. Given that melanopsin is expressed in foetal human retinas, these findings support the idea that the eyes of foetal and early preterm infants are likely to exhibit functional photosensitivity.\n\nKey pointsO_LIMelanopsin is a light-excitable photopigment expressed in a subset of ganglion cell neurons (mRGCs) in the retinas of many different species of vertebrates. In mature animals, light activation of mRGCs modulates many visual adaptive functions including pupil constriction, entrainment of circadian rhythms, mood and learning. In neonatal pups at ages prior to the developmental onset of visual signalling from rods and cones, melanopsin cells mediate photoaversive behaviour. In foetal pups, light activation of melanopsin cells accelerates maturation of the ocular vasculature. Here, we describe and physiologically characterize the light responses of melanopsin ganglion cells in the retinas of foetal pups.\nC_LIO_LIMRGCs in embryonic retinas respond to light at least four days prior to birth and exhibit responses to light of intensity as low as 3 x 1012 photons/cm2/s.\nC_LIO_LIPhototransduction mechanisms include melanopsin activation of Gq/11 - G proteins, voltage-activated sodium currents, and voltage-gated L-type calcium currents.\nC_LIO_LIMRGCs are electrotonically coupled to other mRGCs in foetal retinas.\nC_LIO_LIWe propose that melanopsin-expressing ganglion cells are excited by light while in utero and that this excitation relies, for the most part, on phototransduction pathways that have been described in postnatal retinas. Furthermore, we propose that foetal mRGCs have the requisite properties to modulate light-regulated maturation of the ocular vasculature and, perhaps, the development of visual pathways.\nC_LI