Ophthalmology

After discovering a light-dependent molecular pathway that regulates how blood vessels develop in the eye, scientists at Cincinnati Children’s suggest it may be possible to use light therapy to help preterm infants avoid life-long vision problems.

A study in mouse models reveals that normal function of the Opsin 5-dopamine pathway is needed to ensure the correct balance of blood vessel development in the eye. This process can be disrupted in medically fragile preterm infants, with significant consequences.

“Our study indicates that the Opsin 5-dopamine pathway is part of a light-dependent disease process for retinopathy of prematurity” says Richard Lang, PhD, director of the Visual Systems Group and the study’s senior author. “It raises the interesting possibility that we might be able to use light exposure to treat this disease and save the sight of thousands of premature infants.”

Minh-Thanh Nguyen, PhD, formerly a research associate in Lang’s lab, was the study's lead author. Co-authors included Mike Iuvone, PhD, Emory University, as well as Russell Van Gelder, MD, PhD, and Ethan Buhr, PhD, from the University of Washington.

The collaborators used a variety of methods to study eye development and the influence of the Opsin 5-dopamine pathway in postnatal mice. The gene OPN5 and the protein it expresses are highly conserved among species, which makes the mouse findings potentially relevant to human development, Lang says.

Vision requires vascular balance

During postnatal eye development, an embryonic network of hyaloid blood vessels regresses in a process that requires precise timing to allow mice to develop high-acuity vision.

The researchers demonstrate that eye development depends on light responses in the retina that are controlled by Opsin 5, a protein expressed in a subset of retinal ganglion cells. Opsin 5 and the neurotransmitter dopamine—which promotes blood vessel regression—work in unison to regulate vascular development.

The team developed a line of OPN5 knockout mice to show its effect. Without Opsin 5, dopamine levels rose within the vitreous (the clear, gel-like substance in the eye). This caused hyaloid blood vessels to regress very quickly, hindering normal eye development.

Light therapy restored the balance

The researchers also showed that 380-nanometer violet-colored light normally activates signaling via Opsin 5. This suppressed dopamine levels and produced other molecular changes in the eye that produced normal timing and appropriately balanced vascular development.

"From an evolutionary perspective, it may not be surprising that biological pathways use 380 nm light, because it is present in the natural sunlight spectrum,” Nguyen says. “However, artificial lighting systems that do not produce this wavelength may be insufficiently activating this response."

Lang says more preclinical study is required before these mouse-based findings can be evaluated in a human clinical trial.

Citation

Nguyen MT, Vemaraju S, Nayak G, Odaka Y, Buhr ED, Alonzo N, Tran U, Batie M, Upton BA, Darvas M, Kozmik Z, Rao S, Hegde RS, Iuvone PM, Van Gelder RN, Lang RA. An opsin 5-dopamine pathway mediates light-dependent vascular development in the eye. Nat Cell Biol. 2019 Apr;21(4):420-429.