“Three Blind Mice”…
Three blind mice. Three blind mice.
See how they run. See how they run.
They all ran after the farmer's wife,
Who cut off their tails with a carving knife,
Did you ever see such a thing in your life,
As three blind mice?

THREE BLIND MICE: SEE HOW THEY SEE You’re probably familiar with the nursery rhyme



This nursery rhyme from merry old England actually had nothing to do with mice running after the farmer’s wife and getting their tails whacked off. It was about Catholics murdering Protestants in Great Britain. The farmer’s wife was Queen Mary I—“Bloody Mary”—an ardent Catholic with vast real estate holdings. She didn’t dismember three blind mice. Rather, she burned three Protestant noblemen at the stake after they were caught plotting against her.

But that’s not the subject of this column. It’s also not about:

* The HSUS filing a ballot issue to protect mice
* Governor Strickland pardoning the mice in his last days in office
* The Ohio Livestock Animal Welfare Board establishing mice welfare guidelines

Instead, I’m writing to share some encouraging news for mice and men.

Scientists have found a way to use biotechnology to restore sight in blind mice afflicted with retinal and macular degeneration – conditions that affect millions of Americans.

Think about it! Blind mice can see where they run. What will this mean for us humans?

Problem Solved

A retinal prosthesis has been developed for blind mice. Combined with gene therapy, the prosthesis—grafted into the eye—deciphers visual stimuli from the eye to the brain, enabling once blind mice to see clearly. (In case you were wondering, I will report later in this column how one tests a mouse’s vision.)

In a healthy eye, light stimulates the photoreceptors of the retina, in the back of the eye, to process and send the information to the nerve transport (ganglion) cells. Ganglion cells carry these signals to the brain as a specific pattern of chemo-electrical activity.

Mice and people with retinal and macular degeneration, because of a loss of the photoreceptors contained in the retina, lose the ability to transmit visual messages to the brain.

Early versions of the retinal prosthesis only stimulated nerve transport cells directly and produced no visual code for the brain. A subject with these early implants was only able to distinguish light from dark and, perhaps, walls and corners. The brain couldn’t interpret these visual stimuli because they weren’t accompanied by a chemo-electrical code for the brain to interpret.

The Research

Sheila Nirenberg and her colleagues at Weill Cornell Medical College in New York compared the signals generated in healthy, sighted mice and blind mice. With this comparison the researchers produced a copy of the complex formula (algorithm) that sighted mice sent to the brain for interpretation into visual cues.

It was discovered that blind mice lacked the chemical trigger, channelrhodopsin, which makes ganglion cells respond to light and send chemo-electrical stimuli to the brain. Nirenberg used gene transfer therapy to stimulate blind mouse eyes to produce channelrhodopsin.
One last step was needed to confirm that the researchers’ strategy would work. They outfitted the mice with glasses, equipped with a tiny, embedded camera to fire rapid pulses of light through LEDs into the mice’s eyes. This stimulated channelrhodopsin in the retina prostheses to send the coded signal cues for sight to the test subjects’ brains.

The Test

To find out if it worked, the researchers showed sighted mice a photo of a cat so they could observe their reactions. They compared the reactions of blind mice as they wore their newly engineered glasses after gene therapy. The blind mice reacted to the cat photo just as the sighted mice did—pretty much like you’d expect a mouse to react to a mouser. Voilà! The blind mice could see!

Nirenberg reported that the “system provides enough information to demonstrate sight being restored to reconstruct face images, newsprint, landscapes, essentially anything.”

Next up is testing the system on primates. Nirenberg has teamed up with a University of Florida geneticist who developed a method for the required gene therapy in primates and humans. If the primate research goes well, next up is humans. A California company, Second Sight, already has a human retinal implant waiting in the wings for this new technology to catch up.

As far as the mice at our house, their vision is already too sharp. Every fall they scope out the silverware drawer in Judy’s kitchen. I don’t get any rest until I trap those little scamps. It is hard enough keeping up with normally sighted mice. All I need is to have super-sighted, spectacle-wearing mice scoping out every last crumb to chew.