The Müller glial cells: are specialized glia for light detection in the retina?

MARCHESE, NATALIA A.; RIOS, MAXIMILIANO N.; GUIDO, MARIO E.

Buenos AIres- formato híbrido

Encuentro; FIRST MEETING GLIA CLUB SOUTHERN CONE; 2022

The retina of vertebrates captures ambient light for image and non-image forming (NIF) functions through two sets of specialized photoreceptors: cones and rods responsible for day/night vision, and intrinsically photosensitive retinal ganglion and horizontal cells expressing melanopsin (Opn4). Interestingly, Müller glial cells (MCs), which are derived from neuronal progenitors and represent the most abundant retinal glial cell type, have been shown to express different blue- and uv-light sensitive opsins (Opn3 and Opn5) and the photoisomerase retinal G protein-coupled receptor (RGR). Here we resume our most recent results showing intrinsic cellular responses in primary cultures of avian MCs elicited by blue light stimulation (peak at 480 nm). By means of intracellular calcium level detection with fluorescent probes and real-time microscopy, we identified a subpopulation of MCs (40% of recorded cells) showing direct photic responses, observed as a ˃20% increase in intracellular calcium levels and maintained for several minutes after the stimulus. The calcium response was shown to be dependent on opsin activation and specific to blue light stimulation. Light-evoked responses in MC cultures were suppressed by up to 50% after depleting endoplasmic reticulum calcium stores with thapsigargin; no significant inhibition was achieved by modifying extracellular calcium availability with the calcium chelator EGTA. Further testing were performed with the inhibitors for IP3 receptors (2-APB), protein kinase C (U73122) and G protein-coupled receptors (Suramin). Under these conditions, the subpopulation of MCs responding to light with calcium increase was diminished. This would indicate that blue light stimulation in MCs promotes increases in calcium intracellular levels by G-protein signaling towards calcium mobilization from internal stores, pointing at the possibility of a higher level of complexity for light detection in the retina involving photic activation of MCs in light-regulated circuits and pathways.