Armed with a new ability to find retinal anomalies at the cellular
level, neurobiologists at St. Jude Children's Research Hospital have
made a discovery they hope will ultimately lead to a treatment for
cancer of the retina.
While much work remains, Oak Ridge National Laboratory's specialized
tracing algorithm allows researchers to analyze thousands of cells
instead of just a few dozen. This tool has helped reveal a previously
undiscovered role of Rb, the retinoblastoma tumor suppressor gene in the
developing retina. The findings are detailed in a paper published in
the Proceedings of the National Academy of Sciences, available at http://www.pnas.org/content/early/2011/12/08/1108141108.abstract.
"Our paper shows that horizontal neurons known to be deficient in
this gene exhibited abnormalities in the way their dendrites – the arms
that connect to other cells – were organized after a certain number of
days after birth," said the Department of Energy lab's Ryan Kerekes, one
of the authors. The images of mouse retinas were acquired using
confocal microscopy while The Jackson Laboratory provided the mice.
To make their discovery, Kerekes, ORNL colleague Shaun Gleason and
postdoc Mahmut Karakaya developed a computer program and automated tool
that traces the very complex and intricate dendritic arbor. This tool
allows scientists to draw a line along each branch in the neuron's tree
of connectors so the branch can be measured in terms of length, angle
and other parameters.
"Previously, this was a very time-consuming and labor-intensive
process," Kerekes said. "Existing commercial software tools were not
tuned to this particular data and, as a result, produced too many
tracing errors."
As a result, only a handful of cells could be analyzed in sufficient
detail, according to Kerekes, who noted that the ORNL tracing
algorithms achieves the level of accuracy required to analyze thousands
of developing neurons.
Retinoblastoma is caused by a mutation in a gene controlling cell
division, causing cells to grow out of control and become cancerous. It
is most commonly found in children 2 and younger.
While this paper focused on cancer of the retina, Gleason noted that
this research focuses on a number of retinal developmental issues.
