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

Nat Cell Biol. 2019 Apr;21(4):420-429. doi: 10.1038/s41556-019-0301-x. Epub 2019 Apr 1.

Abstract

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 opsin 5 (OPN5; also known as neuropsin)-dependent retinal light responses regulate 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 the activity of inner retinal DAT (also known as SLC6A3; a dopamine reuptake transporter) and thus suppresses vitreal dopamine. In turn, dopamine acts directly on hyaloid vascular endothelial cells to suppress the activity of vascular endothelial growth factor receptor 2 (VEGFR2) and promote hyaloid vessel regression. With OPN5 loss of function, the vitreous dopamine level 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Dopamine Plasma Membrane Transport Proteins / chemistry
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Endothelium, Vascular / metabolism
  • Eye / blood supply*
  • Eye / enzymology
  • Eye / growth & development
  • Eye / metabolism
  • Light*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Opsins / genetics
  • Opsins / metabolism*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / radiation effects
  • Threonine / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / physiology
  • Vitreous Body / metabolism

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Proteins
  • OPN5 protein, mouse
  • Opsins
  • Slc6a3 protein, mouse
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • Threonine
  • Dopamine