Light Exposure During Pregnancy Key to Normal Eye Development

New research in Nature concludes the eye – which depends on light to see – also needs light to develop normally during pregnancy.

Scientists say the unexpected finding offers a new basic understanding of fetal eye development and ocular diseases caused by vascular disorders – in particular one called retinopathy of prematurity that can blind premature infants. The research, led by scientists at Cincinnati Children’s Hospital Medical Center and the University of California, San Francisco (UCSF), appears online Jan. 16 ahead of print publication.

“This fundamentally changes our understanding of how the retina develops,” says study co-author Richard Lang, PhD, a researcher in the Division of Pediatric Ophthalmology at Cincinnati Children’s Hospital Medical Center. “We have identified a light-response pathway that controls the number of retinal neurons. This has downstream effects on developing vasculature in the eye and is important because several major eye diseases are vascular diseases.”

Lang is a principal investigator on the ongoing research along with project collaborator, David Copenhagen, PhD, a scientist in the departments of Ophthalmology and Physiology at UCSF. The scientists say their current study, conducted in mouse models, includes several unexpected findings.

"Several stages of mouse eye development occur after birth," says Copenhagen. "Because of this, we had always assumed that if light played a role in the development of the eye, it would also happen only after birth."

But researchers in the current study found that activation of the newly described light-response pathway must happen during pregnancy to activate the carefully choreographed program that produces a healthy eye. Specifically, they say it is important for a sufficient number of photons to enter the mother’s body by late gestation, or about 16 days into a mouse pregnancy.

Researchers were also surprised to learn that photons of light activate a protein called melanopsin directly in the fetus – not the mother – to help initiate normal development of blood vessels and retinal neurons in the eye.

One purpose of the light-response pathway is to suppress the number of blood vessels that form in the retina. These vessels are critical to retinal neurons, which require large amounts of oxygen to form and to function. When retinopathy of prematurity occurs in infants, retinal vessels grow almost unchecked. This continued expansion puts intense pressure on the developing eye and in extreme cases causes severe damage and blindness.

The research team led by Lang and Copenhagen conducted several experiments in laboratory mouse models that allowed them to identify the light-response pathway’s specific components and function.

Mice were reared in the dark and in a normal day-night cycle beginning at late gestation to observe the comparative effects on vascular development of the eye. The researchers verified the function of the light response pathway by mutating an opsin gene in mice called Opn4 that produces melanopsin, in essence preventing activation of the photo pigment.

Both mice reared under dark conditions from late gestation, and those with mutated Opn4, exhibited nearly identical promiscuous expansion of hyaloid vessels and abnormal retinal vascular growth. The unchecked vascular growth was driven by the protein vascular endothelial growth factor (Vegfa). When the light response pathway is properly engaged, it modulates Vegfa to help prevent promiscuous vascular growth, according to researchers.

The melanopsin protein is present in both mice and humans during pregnancy. Lang said the research team is continuing to study how the light-response pathway might influence the susceptibility of pre-term infants to retinopathy of prematurity and also be related to other diseases of the eye.

Human Eye Gives Researchers Visionary Design for New, More Natural Lens Technology

Drawing heavily upon nature for inspiration, a team of researchers has created a new artificial lens that is nearly identical to the natural lens of the human eye. This innovative lens, which is made up of thousands of nanoscale polymer layers, may one day provide a more natural performance in implantable lenses to replace damaged or diseased human eye lenses, as well as consumer vision products; it also may lead to superior ground and aerial surveillance technology.

This work, which the Case Western Reserve University, Rose-Hulman Institute of Technology, U.S. Naval Research Laboratory, and PolymerPlus team describes in the Optical Society’s (OSA) open-access journal Optics Express, also provides a new material approach for fabricating synthetic polymer lenses.

The fundamental technology behind this new lens is called “GRIN” or gradient refractive index optics. In GRIN, light gets bent, or refracted, by varying degrees as it passes through a lens or other transparent material. This is in contrast to traditional lenses, like those found in optical telescopes and microscopes, which use their surface shape or single index of refraction to bend light one way or another.

“The human eye is a GRIN lens,” said Michael Ponting, polymer scientist and president of PolymerPlus, an Ohio-based Case Western Reserve spinoff launched in 2010. “As light passes from the front of the human eye lens to the back, light rays are refracted by varying degrees. It’s a very efficient means of controlling the pathway of light without relying on complicated optics, and one that we attempted to mimic.”

Using the Eye as a ‘Window Into the Brain’

An inexpensive, five-minute eye scan can accurately assess the amount of brain damage in people with the debilitating autoimmune disorder multiple sclerosis (MS), and offer clues about how quickly the disease is progressing, according to results of two Johns Hopkins studies.

“The eye is the window into the brain and by measuring how healthy the eye is, we can determine how healthy the rest of the brain is,” says Peter A. Calabresi, M.D., a professor of neurology at the Johns Hopkins University School of Medicine, and leader of the studies described in recent issues of The Lancet Neurology and the Archives of Neurology. “Eye scans are not that expensive, are really safe, and are widely used in ophthalmology, and now that we have evidence of their predictive value in MS, we think they are ready for prime time. We should be using this new quantitative tool to learn more about disease progression, including nerve damage and brain atrophy.”

Calabresi and his colleagues used optical coherence tomography (OCT) to scan nerves deep in the back of the eye, applying special software they co-developed that is capable of assessing previously immeasurable layers of the light-sensitive retinal tissue. The scan uses no harmful radiation and is one-tenth the cost of an MRI. The software will soon be widely available commercially.

Reverse-Engineered Irises Look So Real, They Fool Eye-Scanners

The work goes a step beyond previous work on iris-recognition systems. Previously, researchers have been able to create wholly synthetic iris images that had all of the characteristics of real iris images — but weren’t connected to real people. The images were able to trick iris-recognition systems into thinking they were real irises, though they couldn’t be used to impersonate a real person. But this is the first time anyone has essentially reverse-engineered iris codes to create iris images that closely match the eye images of real subjects, creating the possibility of stealing someone’s identity through their iris.

“The idea is to generate the iris image, and once you have the image you can actually print it and show it to the recognition system, and it will say ‘okay, this is the [right] guy,’” says Javier Galbally, who conducted the research with colleagues at the Biometric Recognition Group-ATVS, at the Universidad Autonoma de Madrid, and researchers at West Virginia University.

Caption: Brain and eye anatomy. Computer artwork of the brain from below, with the front of the brain and the eyeballs (both sectioned) at top. Nerves (yellow) include the optic nerves, the olfactory nerves (between the optic nerves), and the upper part of the spinal cord (lower centre). The cerebellum has been removed, and the brain made transparent to show the limbic structures (centre). The brainstem is above the spinal cord. At bottom are the occipital lobes (red), the visual processing centres at the rear of the brain. The optic nerves cross at the optic chiasma (centre), allowing the images from both eyes to be combined.

Credit: SPRINGER MEDIZIN/SCIENCE PHOTO LIBRARY