Research defines eye cancer gene's role in retinal development

A genetic discovery led by scientists at St. Jude Children’s Research Hospital helps answer a long-standing mystery about the eyes of vertebrates, and may translate into a deeper understanding of how genes coordinate the complex process of eye formation and how a rare pediatric eye cancer progresses.

“A series of complex developmental processes must be carefully orchestrated for the eye to form correctly,” said Michael Dyer, Ph.D., associate member in the St. Jude Department of Developmental Neurobiology. “One important aspect of this coordination is that retinal thickness be the same, irrespective of eye size. For example, the mouse eye is about 5,000 times smaller than that of the elephant eye, but the retinal thickness in these two species is comparable.”

Working with mice, the researchers found that a gene called N-myc coordinates the growth of the retina and other eye structures to ensure the retina has the proper thickness necessary to convert light from the lens into nerve impulses that the brain transforms into images. Until their study, reported in the Jan. 15 issue of “Genes & Development,” almost nothing was known about the molecular mechanisms responsible for properly sizing the retina. Dyer is the paper’s senior author.

“This represents the first example of a role for a Myc gene in retinal development,” Dyer said. “On the basis of our data, we propose that N-myc plays a central role in coordinating retinal proliferation with eye growth during development.”

Genes in the Myc family carry out vital roles during prenatal development by regulating the proliferation, size, differentiation and survival of cells. Myc genes are also proto-oncogenes—genes in which a mutation enables them to transform normal cells into cancerous ones. Malfunctioning N-myc genes are often associated with pediatric neural cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Recently, Dyer and his team identified the specific type of cell that gives rise to retinoblastoma, a potentially fatal malignant tumor in the retina that affects about 300 children in the United States annually. “The determination of N-myc target genes during retinal development may also contribute to the current understanding of retinoblastoma progression,” he said.

In the course of their study, the researchers discovered that N-myc is not involved in regulating cell survival or neuronal differentiation in the developing retina. However, the gene is crucial for the proper proliferation of retinal cells. In mice in which the scientists inactivated N-myc, the volume of the retina was significantly smaller than in mice with normally functioning N-myc.

The team found no evidence of an increase in progenitor cell deaths between normal and N-myc-deficient retinas. The investigators then concluded the smaller retinas likely resulted from an N-myc-related proliferation defect in the progenitor retinal cells.

The researchers hypothesize that N-myc’s activity occurs early in the cascade of reactions that control development of the retina and other eye components. Therefore, when something inactivates the gene, the result is both a reduction in retinal progenitor cell proliferation and a reduction in the signaling cues that coordinate the growth of the eye and retina.

“Importantly, for retinas to maintain nearly constant thickness across species that have different sizes of eyes, the total number of retinal cells must change several-fold,” Dyer said. “The identification of N-myc as a key regulator of these processes allows us to begin to understand the coordination of complex developmental programs in the developing eye and how these processes have evolved.”

Source: St. Jude Children's Research Hospital

Related stories:

Protein transports nutrients believed to protect against eye disease
Scientists have identified the protein responsible for transporting nutrients to the eye that are believed to protect against the development of age-related macular degeneration, a leading cause of vision loss in elderly Americans.
'Snapshots' of eyes could serve as early warning of diabetes
A new vision screening device, already shown to give an early warning of eye disease, could give doctors and patients a head start on treating diabetes and its vision complications, a new study shows.
Retina transplants show promise in patients with retinal degeneration
Preliminary research shows encouraging results with transplantation of retinal cells in patients with blindness caused by retinitis pigmentosa (RP) and age-related macular degeneration (AMD), according to a report in the August issue of American Journal of Ophthalmology.
Microchip is helping restore vision to the blind
Last year, Wentai Liu watched as surgeons implanted a microchip he had designed into the eye of a blind patient. For Liu, a professor of electrical engineering in the Baskin School of Engineering at the University of California, Santa Cruz, it was a major milestone in two decades of work on an artificial retina to restore vision to the blind.
Perfect Vision But Blind To Light
Mammals have two types of light-sensitive detectors in the retina. Known as rod and cone cells, they are both necessary to picture their environment. However, researchers at the Salk Institute for Biological Studies have found that eliminating a third sensor — cells expressing a photopigment called melanopsin that measures the intensity of incoming light —makes the circadian clock blind to light, yet leaves normal vision intact.
Gene therapy involving antibiotics may help patients with Usher syndrome
A new approach to treating vision loss caused by Type 1 Usher syndrome (USH1), the most common condition affecting both sight and hearing, will be unveiled by a scientist at the annual conference of the European Society of Human Genetics today. Ms Annie Rebibo Sabbah, from the Genetics Department of the Rappaport Faculty of Medicine, Technion, Haifa, Israel, will tell the conference that preliminary results using a class of drugs called aminoglycosides, commonly used as antibiotics, had had promising effects in vitro and in cell culture.
Anti-HIV drugs reduce the cause of some forms of vision loss
A potential new therapeutic use for anti-HIV drugs known as protease inhibitors has been suggested by a team of researchers from Harvard Medical School, Boston, and Inserm U848, France, as a result of their work in a mouse model of retinal detachment.
Sight Recovery After Blindness Offers New Insights on Brain Reorganization
Studies of the brains of blind persons whose sight was partially restored later in life have produced a compelling example of the brain's ability to adapt to new circumstances and rewire and reconfigure itself.

News discussion:

Medicine & Health news