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.
Minh-Thanh T Nguyen  1  2 ,  Shruti Vemaraju  1  2 ,  Gowri Nayak  1  2 ,  Yoshinobu Odaka  1  2 ,  Ethan D Buhr  3 ,  Nuria Alonzo  1 ,  Uyen Tran  1 ,  Matthew Batie  4 ,  Brian A Upton  1  2 ,  Martin Darvas  5 ,  Zbynek Kozmik  6 ,  Sujata Rao  7 ,  Rashmi S Hegde  8 ,  P Michael Iuvone  9  10 ,  Russell N Van Gelder  3  5  11 ,  Richard A Lang  12  13  14  15
Affiliations
  • 1. The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 2. Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 3. Department of Ophthalmology, University of Washington Medical School, Seattle, WA, USA.
  • 4. Clinical Engineering, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 5. Pathology, University of Washington Medical School, Seattle, WA, USA.
  • 6. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
  • 7. Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA.
  • 8. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • 9. Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA.
  • 10. Pharmacology, Emory University School of Medicine, Atlanta, GA, USA.
  • 11. Biological Structure, University of Washington Medical School, Seattle, WA, USA.
  • 12. The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. [email protected].
  • 13. Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. [email protected].
  • 14. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. [email protected].
  • 15. Department of Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA. [email protected].
PMID: 30936473 DOI: 10.1038/s41556-019-0301-x
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.