New vision of a common pest

Former biological sciences doctoral student Jason Meyer understands what's going on behind the beady eyes of a mouse

In mice with a class of neurological diseases called neuronal ceroid lipofuscinoses, or NCLs for short, degeneration of the retina and the entire central nervous system is occurring behind that beady sheen.

Luckily, Jason Meyer knows how to slow it down. With his former mentor, Mark Kirk, professor of biological sciences, Meyer and colleagues Martin Katz, professor of ophthalmology, and Joel Maruniak, associate professor of biological sciences, have used transplanted mouse embryonic stem cells to retard retinal neuron degeneration.

Mice are the model used to understand human NCLs — often referred to as Batten disease. More common to children than adults, some forms of the disease produce symptoms in infants as young as six months of age. Cell death contributes to loss of vision and motor function, seizures, dementia and ultimately premature death.

Thanks to some promising research by Meyer and colleagues, recently published in the journal Stem Cells, treatment options are in sight.

Adult stem cells aren't easy to locate in many tissues, including the eye, Kirk says. They usually develop into the mature cells of the tissue from which they originate. But in this card game of development, embryonic stem cells are wild and have the power to transform into any cells of the body under the correct conditions.

For the study, mouse embryonic stem cells were subjected to conditions that caused them to begin developing into neurons, which are found in the eye. The researchers injected about 45,000 of those cells behind the lens and into the fluid center of a young, diseased mouse's eye, in the hopes that the healthy donor cells would incorporate into the retina, survive and prevent degradation of the retinal neurons.

The eye is the most easily accessible part of the central nervous system, Kirk says. "It's much easier to manipulate because it's out there in the periphery." Vision loss, he says, is also one of the earliest symptoms of the disorder.

After transplant, the researchers examined the mouse retinas at different stages and found promising, colorful results. Cells that had been transplanted into a mouse's eye resembled a fluorescent kids' cereal with yellow blotches, red smudges and green globs. Yellow was the color the researchers wanted to see, says Meyer, now a postdoctoral researcher at the University of Wisconsin-Madison Waisman Center.

Yellow meant not only that the transplanted donor cells were surviving in the host retina long-term, but that the donor cells actually looked and acted like mature retinal neurons. This suggests that embryonic stem cells could possibly be used to replace lost neurons.

Meyer, who completed the research as part of his doctoral dissertation, says there are no other embryonic stem cell studies focused on Batten disease.

The researchers hope their work will eventually allow the development of treatment options for children and adults with NCL using stem cell and gene therapy. "At present there are no effective therapies for any of the NCLs," Kirk says on his lab's Web site.

Thanks to cutting-edge research, this study is an important step toward treating neurodegenerative disease.

Links:

article abstract

Kirk Lab
Joel Maruniak
Division of Biological Sciences

Martin Katz
Department of Ophthalmology