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. Richard.Lang@cchmc.org.
13 Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Richard.Lang@cchmc.org.
14 Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Richard.Lang@cchmc.org.
15 Department of Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, OH, USA. Richard.Lang@cchmc.org.

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/KDR/Flk-1) 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.

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