A novel study conducted by an international team of researchers has identified a protein that plays key role in eye development.
Scientists from John Hopkins University School of Medicine and Washington University School of Medicine have found a protein called Pias3 that regulates how the light-sensing nerve cells in the retina form.
Advertisement"We've found a protein that seems to serve as a general switch for photoreceptor cell development," said Seth Blackshaw, Ph.D., an assistant professor in the Solomon H. Snyder Department of Neuroscience at Johns Hopkins.
"This protein coordinates the activity of multiple proteins, acting like a conductor of an orchestra, instructing some factors to be more active and silencing others, and thus contributing to the development of light-sensitive cells of the eye," he added.
During the study, the researchers were interested in how other genes that are active in the developing retina can act to promote the development of rod cells while suppressing the development of cone cells.
While rod cells help us see in dim or dark light, and cone cells help us see bright light and color, the loss of cone cells in particular can lead to irreversible blindness.
They looked at the candidate protein Pias3, short for protein inhibitor of activated Stat3.
Pias3 was known to alter gene control in cells outside of the eye. In these cells, Pias3 doesn't directly turn genes on and off, but instead adds a chemical tag, through a process called SUMOylation, to other proteins that do switch genes on and off.
And, since Pias3 also is found in developing rod and cone and no other cells in the eye, the team hypothesized that it might act to help these cells "decide" which type to become.
In the new study, scientists engineered mice to make more Pias3 than normal in the eye and counted rod and cone cells.
Those eyes contained more rod cells than eyes from mice containing a normal amount of Pias3 protein. When they reduced the amount of Pias3 in developing mouse eyes, they found that the cells that might otherwise have been rod cells instead developed into conelike cells. So the team concluded that Pias3 promotes rod cell development and suppresses cone cell development.
For further analysis, the team altered the Pias3 protein to disrupt its SUMOylation activity.
They found that eyes containing altered Pias3 did not develop the correct number of rod cells, suggesting that Pias3's SUMOylation activity was the key to its ability to promote rod and suppress cone cell development in the eye.
The study appears in journal Neuron.