Encephalopsin (Opn3) is transiently expressed in Opn5+ retinal ganglion cells and regulates retinal clock dynamics

Abstract

By Reena Jacob, Biological Sciences

Advisor: Richard Lang

Abstract: The retina is a light-sensitive tissue located in the back of the eye, and aside from its role as input for image-forming vision, retinal signaling is a major input into the circadian clock system. In mammals, the master clock (suprachiasmatic nucleus; SCN) receives input from the retina, and relays time-of-day information to peripheral tissues, thus aligning local tissue clocks (skin, gut, etc.) with the light-dark cycle. However, it has become increasingly clear that peripheral tissues can synchronize their clocks with the light-dark cycle autonomously through expression of atypical opsins. One such tissue is the retina, whose clock-phase is dependent on Opn5. Curiously, in identifying the essential entrainment photopigment protein, we identified Opn3 as a putative regulator of clock dynamics in the retina. While loss of Opn3 does not alter the phase of the retinal clock, it appears to severely reduce the clock's amplitude. This led us to hypothesize that Opn3 and Opn5 reside in the same cell type, and modulate differential parameters - clock amplitude and phase, respectively. Here, we test this hypothesis and show that Opn3 is expressed in retinal ganglion cells as early as E17.5 in the mouse, but the overlap between Opn3 and Opn5 is transient. Deletion of Opn3 failed to elicit developmental alterations in cell types associated with the retinal clock, suggesting that the clock amplitude reduction is not a consequence of fewer oscillating cells. These data warrant further exploration of the means by which local clock rhythms are generated and maintain