Neuropsin-expressing cells in the retina affect melanopsin expression and response to light in mice

Neuropsin (OPN5) is an opsin involved in several non-image forming functions in the retina, such as the photoentrainment of the retinal circadian clock. These roles were previously attributed to melanopsin (OPN4) which prompted the hypothesis that OPN4 and OPN5 functionally interact. However, the specific cells expressing OPN5 and their interactions with the broader photoreception system remain unclear. This study aims to characterize OPN5-expressing cells and assess how their absence influences the photoresponses of OPN4-expressing cells. Through the use of genetically encoded reporters, confocal microscopy and serial blockface electron microscopy, we identified and reconstructed OPN5-cells and their processes. OPN5 expression was found in a small number of various retinal ganglion cell (RGC) subtypes, without overlap with OPN4-expressing cells, and presented distinct dendritic arborization patterns. In parallel, we measured the retinal electrical response to light in mice lacking either OPN4 or OPN5 to determine the contribution of each opsin and the consequences of their absence. Mice deficient in OPN5 exhibited reduced maximal discharge rates upon stimulation of light, though response duration remained unchanged. No specific electrical response to UV light was detected in OPN5-expressing cells suggesting that the response of OPN5 cells to light is translated in non-electrical pathway.