New steps towards reducing the incidence of myopia: stimulation by violet light proves effective

The global incidence of myopia (short-sightedness) has increased significantly in recent years, and the condition is estimated to be affecting one third of the human population. If the incidence continues to grow at its current pace, it is predicted that 5 billion people worldwide will have developed myopia by 2050. The increase in the incidence of myopia is especially evident in countries in Asia, with a recent survey showing that 95% of students in junior high schools in Tokyo have the condition.

In international research collaboration with Professor Machelle Pardue of the Georgia Institute of Technology and Professor Richard Lang of Cincinnati Children's Hospital, the research group made up of Professor Emeritus Kazuo Tsubota (CEO of Tsubota Laboratory, Inc.), Lecturer Toshihide Kurihara (currently a university hospital intern), PhD student Xiaoyan Jiang, and others at the School of Medicine at Keio University has discovered that the nonvisual photoreceptor OPN5 (neuropsin) expressed in retinal ganglion cells suppresses myopia progression by receiving short-wavelength visible light. In 2016, the research group reported for the first time in the world that visible light with a wavelength of 360-400 nanometers (violet light) suppresses myopia progression, and after further investigation, they discovered its mechanism in this study. Their findings were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS).

OPN5 is a photoreceptor that was discovered in recent years and has a maximum absorption wavelength of 380 nanometers in the violet light region in humans and mice. It has been reported that OPN5 does not contribute to vision, unlike the photoreceptors expressed in retinal visual cells. Rather, it is involved in the circadian rhythm in the retina, angiogenesis in the eye, and the regulation of the core body temperature. However, its full functions remain unknown. In this study, the research group managed to get OPN5-expressing mouse cells to express a fluorescent dye by mating genetically modified mice that express OPN5-specific Cre recombinase with mice carrying a fluorescent reporter. The results showed that OPN5 is expressed in some retinal ganglion cells located in the inner layer of the mouse retina.

Using a mouse model of myopia that was previously developed by the research group, axial length elongation, which is similar to myopia in humans, could be induced. Exposure of the mice to violet light for 3 hours a day resulted in the suppression of axial length elongation of the eye, which had been observed in a chick model of myopia and in human patients. However, the suppressive effect of violet light on axial length elongation (i.e., the myopia progression-suppressing effect) was not observed in mice lacking the Opn5 gene in retinal neurons specifically. These results suggest that OPN5 expressed by retinal ganglion cells in the inner layer of the retina suppresses myopia progression by receiving violet light in the eye.

Next, the research group focused on the changes in choroidal thickness. Choroidal thinning during myopia progression is well known clinically, and significantly thin choroids may be observed in patients with severe myopia. In this study, the researchers found that the choroidal thickness, which becomes thinner with the induction of myopia, could be maintained through violet light exposure, whereas the maintenance effect was absent in Opn5-knockout mice. These results indicate that the stimulation of OPN5 with violet light controls the choroidal thickness and suggest that changes in the choroidal thickness affect axial length elongation (myopia progression).

While revealing the mechanism of the action of violet light, this study also showed the novel physiological function of the nonvisual photoreceptor OPN5, thereby providing a solid basis for the future development of myopia prevention measures and treatment strategies. The study revealed that light reception in the retina plays an important role not only in vision but also in maintaining the homeostasis of the living body. By targeting nonvisual photoreceptors, we may be able to control the progression of myopia in the future, leading to a reduction in its incidence which is significantly increasing in modern society.