• By Anni Griswold
    Science
    Comprehensive Ophthalmology, Retina/Vitreous

    Biologists from Johns Hopkins have exposed the origins of color vision in a developing fetus by studying the 9-month gestation of human retinas in a laboratory dish. Their study uncovers a key regulator of color vision, according to an October 12 paper in the journal Science.

    After tracing the development of photoreceptor subtypes in hundreds of human retinal organoids, scientists say thyroid hormone—delivered at precisely the right time—sparks the assembly of red-green cones. The discovery could drive new therapies for color blindness and explain why premature infants are prone to certain vision disorders.

    The underpinnings of color vision have been difficult to parse because the mechanism develops in the womb. Researchers have tried to replicate the process in mice, flies and fish, but those models lack the visual nuances seen in humans.

    To skirt these challenges, teams from Johns Hopkins and elsewhere have cultivated human retinal organoids from embryonic stem cells.

    “Everything we examine looks like a normal developing eye, just growing in a dish,” said senior author Robert Johnston, a developmental biologist at Johns Hopkins. “What’s really pushing the limit here is that these organoids take 9 months to develop, just like a human baby. So what we’re really studying is fetal development.”

    As the immature retinal cells matured into a fully functioning retina—mirroring the onset of color vision in a gestating human fetus—the researchers noticed that a surge in thyroid hormone levels acts as a molecular switch by halting formation of blue cones and provoking assembly of red-green cones.

    The researchers manually activated this switch by bathing the organoids in an active form of thyroid hormone. But the retina, they discovered, carefully schedules this surge to occur in late development after a sufficient stock of blue cones has been assembled. The switch is flipped by fine-tuning expression of the thyroid hormone receptor and of an enzyme that converts thyroid hormone to an active form.  

    The findings could help explain why preterm infants have elevated rates of visual problems. Premature birth halts the transfer of thyroid hormone from mother to fetus, leaving preterm infants with low levels of the hormone and limiting the surge that otherwise takes place in late development.   

    Solving the mystery of cone development brings scientists “closer to being able to restore color vision for people who have damaged photoreceptors,” said lead author Kiara Eldred, a graduate fellow at Johns Hopkins. “This is a really beautiful question, both visually and intellectually – what is it that allows us to see color?”