22 May 2009

One Gene, One Vision

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New genetic discoveries explain how it is possible to build very different kinds of eyes with the same genes

Since his seminal 1994 discovery of the Pax-6 gene as the universal master switch of eye formation, Professor Walter Gehring had to prove his point by expressing the mouse gene on the wings and legs of the fruit fly. It worked wonders: not only could he induce extra eyes in funny places on the insect’s body, but he could show they were fully functional. “The mouse gene substituted the fly gene completely, which was amazing”, he recalls.

The Pax-6 gene is at the top of a gene hierarchy working “like a computer program”. Within the “Cells into Organs” project he actually succeeded in deciphering the whole eye development program of the fruit fly. “We have compared this with the mouse and, surprisingly, we found out that 65% of the mouse retina genes are also in the fly. This means you can build very different kinds of eyes with the same genes”.

This is further proof, Professor Gehring adds, that there is only one eye prototype. All the master control genes, including the supporting ones at the next level, “are shared and you can find them all the way down to jellyfish”. This gene hierarchy was firmly established within the “Cells into Organs” project. The purpose of such a research is obviously therapeutic: it’s about finding out how an eye is formed and maintained.

By what he calls “genetic tricks” Professor Gehring can take out the Pax-6 gene in the adult mouse and see that the retina degenerates quite rapidly. It’s as if some eye cells always had to have the input of Pax-6 to signal to the others that they are eye cells. So, a disease like age-related macular degeneration, which strikes older people with a previously good eyesight, “could possibly be cured by activating Pax-6 again or by reinforcing it”, he says.

So, Pax-6 and other genes become weaker with age, but since Pax-6 is at the top of the hierarchy, Professor Gehring is confident that you can reach down to all the subordinate genes by switching it on. Now he wants to “give the mice a shot of Pax-6 to prevent or maybe postpone this degeneration in humans”, perhaps by 20-odd years, in which case old people would not be losing their eyesight anymore. His team is now preparing for an experiment in which they are going to inject Pax-6 behind the retina or into the corpus vitreus of the eye via an absolutely innocuous carrier virus most of us have.



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