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Clues to development of eye's light-sensitive cells found

ke up almost 95% of the photoreceptors in human retina. Much less is known about cones, including the important but puzzling question as to why they do not generally survive without rods in diseases like RP.

Swaroop believes that the Nrl knockout mouse - that is, the mouse bred to have only cone cells - can be used to investigate this behavior. Even though the mice do not have a well-defined macula (a region of the retina that is richer in cones than other parts of the retina), Kellogg researchers hope that this mouse model will allow them to identify the molecules needed for cone function and survival. This knowledge holds promise for developing treatments for macular degeneration, a disease in which photoreceptors in the macular area of the retina die off.

As part of the study, researchers also examined the effect of age on cone function in the absence of rods, recording electrical activity in the retina of Nrl knockout mice at different times after birth. The responses did not change significantly up to 31 weeks, suggesting that cones can survive without rod function. This finding has encouraged Swaroop and colleagues to continue to explore how to keep cones alive longer.

The Nrl gene was discovered by Swaroop's group in 1991 at the Kellogg Eye Center. Over the years, his laboratory has shown that Nrl is a key molecule, which controls the expression of rod-specific genes, including rhodopsin, the visual pigment contained in rods.

Recently, Prabodha K. Swain, Ph.D., a post-doctoral fellow at Kellogg, working with investigators at University of Pennsylvania and in France, showed that Nrl is present only in rods and not in cones. While these investigations were in progress, Mears started to develop the Nrl-knockout mouse to study the role of Nrl in a living animal.

During development, retinal stem cells differentiate into photoreceptors in response to external and internal cues. Since Nrl is needed for rods to develop, it w
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Contact: Kara Gavin
kegavin@umich.edu
734-764-2220
University of Michigan Health System
6-Nov-2001


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