Blue light compromises cellular fate of intrinsically photosensitive M&uumlller glial cells in the developing chicken retina.

Abstract

M&uumlller glial cells (MCs), the predominant glial population in the retina, interface with all neuronal types to form the structural and functional core of the tissue. Beyond their established homeostatic roles, MCs have emerged as promising endogenous neural stem cells with remarkable regenerative potential. Our recent work identified MCs as novel photosensitive elements of the vertebrate inner retina that express non-visual opsins and respond to brief light stimuli. Direct photic responses manifest as a sustained increase in intracellular calcium levels driven by a G protein-mediated signaling cascade that primarily recruits calcium from the endoplasmic reticulum, highlighting MC photoreception and its roles in retinal physiology. In the present work, we characterize expanded light-directed responses in primary chicken MC cultures, identifying a blue light (BL)-triggered signaling cascade. BL stimulation induces a peak in cAMP levels at 10 min, followed by CREB activation (p-CREB) within 30 min, a temporal profile consistent with observations in ex vivo retinal explants. BL exposure (1 h) at the onset of each cell cycle dampens proliferative capacity and migration while lengthening the cell cycle in both primary chicken MCs and an immortalized human MC cell line compared to dark controls. Furthermore, over time (24, 48, and 72 h), BL exposure reduces the proportion of pluripotent cells (Sox2 positive cells), concomitant with an increase in neuronal progenitors (Tbr2) and no change in glial markers (GS, RGR, GFAP). Finally, mature neuronal markers (TUJ-1 and Brn3) increase in MC cultures 120 h post-BL stimulation. Overall, this work broadens our understanding of BL-triggered signaling cascades in MCs and uncovers photoreception as a potential mechanism driving cell fate in the developing retina.