Animal study reveals 'unexpected' role of horizontal cells in photoreceptor rod and cone cell development of retina
Scientists are developing a clearer picture of how visual systems develop in mammals. The findings offer important clues to the origin of retinal disorders later in life.
In research published this week in the Journal of Neuroscience, University at Buffalo scientists and colleagues focused on a particular protein, called a transcription factor, that regulates gene activity necessary for the development of one type of retinal neuron, the horizontal cells.
The paper is at http://www.jneurosci.org/content/33/32/13053.full.
Horizontal cells process visual information by integrating and regulating input from rod and cone photoreceptors, which allow eyes to adjust to see well in both bright and dim light conditions.
"We have found that activation of the transcription factor named Onecut1 is essential for the formation of horizontal cells," explains Xiuqian Mu, PhD, assistant professor in the departments of Ophthalmology and Biochemistry in the UB School of Medicine and Biomedical Sciences.
The researchers came to this conclusion after creating mice that lacked Onecut1. In these knockout mice, the number of horizontal cells was 80 percent lower than in normal mice.
The researchers were surprised to find that the removal of Onecut1 also had an impact on photoreceptor cells, the rods and cones that absorb light in the retina and convert that energy to an electrical impulse eventually conveyed to the brain.
During development, Mu explains, the removal of Onecut1 only appeared to impact the horizontal cells. However, by the time these mice reached adulthood, around 8 months old, the level of photoreceptor cells in these knockout mice was less than half the normal level.
"Because degradation of photoreceptors is believed to be a major factor in retinal diseases, such as retinitis pigmentosa and Leber's congenital amaurosis, this finding, that horizontal cells are necessary for the normal survival of photoreceptor cells, is novel and significant," says Mu. "Many retinal diseases are manifested by the degeneration of photoreceptor cells."
This finding was unexpected, Mu explains, because most investigations into the degeneration of photoreceptor cells have involved genes that directly affect photoreceptor cell development.
"People haven't been looking at horizontal cells," he says. "We didn't think that they'd be involved in photoreceptor cell degradation.