Insight into our sight: A new view on the evolution of the eye lens

The evolution of complex and physiologically remarkable structures such as the vertebrate eye has long been a focus of intrigue and theorizing by biologists. In work reported this week in Current Biology, the evolutionary history of a critical eye protein has revealed a previously unrecognized relationship between certain components of vertebrate eyes and those of the more primitive light-sensing systems of invertebrates. The findings help clarify our conceptual framework for understanding how the vertebrate eye, as we know it, has emerged over evolutionary time. The work is reported by Sebastian Shimeld at the University of Oxford and colleagues at the University of London and Radboud University in The Netherlands.

Our sight relies on the ability of our eye to form a clear, focused image on the retina. The critical component in focusing is the eye lens, and the physical properties that underlie the transparency of the lens, as well as its ability to precisely refract light, arise from the high concentrations of special proteins called crystallins found in lens cells. Fish, frogs, birds and mammals all experience image-forming vision, thanks to the fact that their eyes all express crystallins and form a lens; however, the vertebrates’ nearest invertebrate relatives, such as sea squirts, have only simple eyes that detect light but are incapable of forming an image. This has lead to the view that the lens evolved within the vertebrates early in vertebrate evolution, and it raises a long-standing question in evolutionary biology: How could a complex organ with such special physical properties have evolved?

In their new work, Shimeld and colleagues approached this question by examining the evolutionary origin of one crystallin protein family, known as the betagamma-crystallins. Focusing on sea squirts, invertebrate cousins of the vertebrate lineage, the researchers found that these creatures possess a single crystallin gene, which is expressed in its primitive light-sensing system. The identification of the sea squirt’s crystallin strongly suggests that it is the single gene from which the vertebrate betagamma-crystallins evolved.

The researchers also found that, remarkably, expression of the sea squirt crystallin gene is controlled by genetic elements that also respond to the factors that control lens development in vertebrates: The researchers showed that when regulatory regions of the sea squirt gene are transferred to frog embryos, these regulatory elements drive gene expression in the tadpoles’ own visual system, including the lens. This strongly suggests that prior to the evolution of the lens, there was a regulatory link between two tiers of genes: those that would later become responsible for controlling lens development, and those that would help give the lens its special physical properties. This combination of genes appears to have then been co-opted in an early vertebrate during the evolution of its visual system, giving rise to the lens.

Source: Cell Press
October 11, 2005

Original web page at


Dietary supplementation of docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations. Baboons were randomized to 5 groups, a breastfed (B) and four formula-fed groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no DHA/ARA (P-); preterm, DHA/ARA supplemented (P+). At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry.

DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus, and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations.

Conclusions: 1) DHA and ARA are found at high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia, 2) DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, however ARA levels are relatively immune to ARA in the diet, 3) supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA.

BioMed Central
July 19, 2005

Original web page at BioMed Central


Artificial retina gets diamond coating

A bionic eye that allows blind people to see has now got a protective coat of diamond that should significantly improve its performance. The silicon chip retinal implant is being developed by Second Sight, a company based in Sylmar, California, along with a consortium of university researchers. The device needs a hermetic case to prevent it from reacting with fluids in the eye. “It’s as if you’re throwing a television into the ocean and expecting it to work,” says the company’s president, Robert Greenberg. “The approach until now has been to lock it in a big waterproof can, but it’s very big and bulky,” he explains.

So researchers have developed an ultrananocrystalline diamond (UNCD) film that is guaranteed to be safe, long-lasting, electrically insulating and extremely tough. The coating can also be applied at low temperatures that do not melt the chip’s microscopic circuits. The UNCD film is the first coating to meet all the necessary criteria for the implant, says Xingcheng Xiao, a materials scientist at Argonne National Laboratory, Illinois, who developed the film. The tiny diamond grains that make up the film are about 5 millionths of a millimetre across. They grow from a mixture of methane, argon and hydrogen passing over the surface of the five-millimetre-square chip at about 400 °C. Xiao and his colleagues have already tested the implants in rabbits’ eyes, and saw no adverse reaction after six months. He will present the results on 1 April at the Materials Research Society meeting in San Francisco, California.

A healthy retina contains rod and cone cells that convert light into electrical impulses, which fly to the brain through the optic nerve. But for millions of people with diseases such as retinitis pigmentosa or macular degeneration, these cells do not work properly. The retinal implant bypasses these diseased cells by electrically stimulating healthy cells that sit beneath them at the back of the eyeball. The patient ‘sees’ using a pair of glasses carrying a tiny video camera that sends digitized images to the implant using radio waves.

The first human trial of Second Sight’s artificial retina has been running since 2002, and it has enabled a formerly blind patient to distinguish between objects such as cups and plates, and even to make out large letters. But with only 16 electrodes, the device does not allow the patient to see a clear picture. For that, thousands of electrodes are needed on the same size of chip, making it even more delicate.

In the first trial, the electronics package was separated from the electrodes and implanted behind the patient’s ear because its casing was so bulky, explains Greenberg. The team’s goal is to integrate everything into a single unit that fits neatly into the eye. Xiao adds that a UNCD coating could be equally useful for other implantable devices, such as biosensors to monitor a patient’s health.

“They’ve managed to create a diamond film that is of considerably higher quality than other methods have managed,” says Doug Shire, a materials engineer at Cornell University in Ithaca, New York, who is part of the Boston Retinal Implant Project. “But the ultimate potential of these devices will only be told in long-term trials,” he adds. Second Sight is planning clinical trials of a 60-electrode device this year, but it may be several more years before the diamond-coated chip is used in humans, says Greenberg.

April 12, 2005

Original web page at Nature


Severed optical nerves can be made to grow again

Damaged optic nerves – which run from the eye to the brain – have been regrown for the first time by scientists working with mice. The researchers believe the technique might one day restore sight to people whose optic nerves have been damaged by injury or glaucoma. It could even help regenerate other nerves in the body, they say.

A team led by Dong Feng Chen, at the Schepens Eye Research Institute in Boston, US, combined two genetic modifications to regrow the optic nerve after it was damaged. First they turned on a gene called BCL-2, which promotes growth and regeneration of the optic nerve in young mice. This gene is normally turned off shortly before birth. They then bred those animals with other mice carrying genetic mutations that reduce scar tissue in injured nerves. The researchers crushed the optic nerves shortly after birth, and found that in young mice – less than 14 days old – between 40% and 70% of the injured optic nerve fibres regrew to reach their target destinations in the brain. No regrowth was seen in injured mice without the genetic modifications. That suggests the mice may have regained some vision, Chen told New Scientist, although the study cannot prove it did.

However, the approach did not work on mice more than two weeks old. This may be because the effect of BCL-2 begins to weaken, and scarring – which takes time to set in – starts to inhibit healing. The study could offer some insight into why mammals tend to lose their ability to regrow nerves after a certain age – a phenomenon that remains largely a mystery, suggest the authors. “Unfortunately, the fountain of youth doesn’t last forever,” says Jerry Silver, a nerve regeneration expert at Case Western Reserve University in Ohio, US, who is not part of the team. “You can only give them two extra weeks” before the regeneration stops. But Silver was impressed by the breakthrough, saying the study had the potential to become a “classic” in the field.

Chen says the relatively simple structure of the optic nerve may shed light on how to repair damage to more complicated systems, such as the spinal cord. To apply the genetic technique to humans, a form of gene therapy would have to be developed, or drugs developed that manipulate gene expression. Chen and her colleagues have applied for two patents on the methods they have developed to stimulate neural cell regeneration and prevent degeneration.

Journal reference: Journal of Cell Science (March 2005 issue)

New Scientist
March 15, 2005

Original web page at New Scientist