An Opsin 5-dopamine pathway mediates light-dependent vascular development in the eye

During mouse postnatal eye development, the embryonic hyaloid vascular network regresses from the vitreous as an adaption for high acuity vision. This process occurs with precisely controlled timing. Here we show that an Opsin 5 (OPN5, Neuropsin)-dependent retinal light response regulates vascular development in the postnatal eye. In Opn5 null mice hyaloid vessels regress precociously. We demonstrate that 380 nm light stimulation via OPN5 and VGAT (the vesicular GABA/glycine transporter) in retinal ganglion cells enhances activity of inner retinal DAT/SLC6A3 (a dopamine reuptake transporter) and thus suppresses vitreal dopamine. In turn, dopamine acts directly on hyaloid vascular endothelial cells to suppress activity of VEGFR2 and promote hyaloid vessel regression. With OPN5 loss-of-function, vitreous dopamine is elevated and results in premature hyaloid regression. These investigations identify violet light as a developmental timing cue that, via an OPN5-dopamine pathway, regulates optic axis clearance in preparation for visual function.