Featured Research

from universities, journals, and other organizations

Critical Switch In Eye Development Discovered

Date:
March 15, 2009
Source:
Johns Hopkins Medical Institutions
Summary:
Researchers have identified a key to eye development -- a protein that regulates how the light-sensing nerve cells in the retina form. While still far from the clinic, the latest results could help scientists better understand how nerve cells develop.

Researchers at the Johns Hopkins University School of Medicine and Washington University School of Medicine have identified a key to eye development — a protein that regulates how the light-sensing nerve cells in the retina form. While still far from the clinic, the latest results, published in the Jan. 29 issue of Neuron, could help scientists better understand how nerve cells develop.

"We've found a protein that seems to serve as a general switch for photoreceptor cell development," says 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."

Blackshaw's laboratory is trying to understand the steps necessary for developing light-sensitive eye cells to transition into one of two types: rod or cone cells. Any breakdown in the development of either type of cell can lead to impaired eyesight and, says Blackshaw, "the loss of cone cells in particular can lead to irreversible blindness." Rod cells help us see in dim or dark light, and cone cells help us see bright light and color.

The research team was 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. So they took a closer look 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.

To determine whether Pias3 orchestrates rod cell development, the researchers used mice. First, they 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.

Next they wanted to know if Pias3 works the same in eye cells as it does in other cells, through SUMOylation. 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 team also found that Pias3 SUMOylates a protein, Nr2e3, already known to influence rod and cone cell development, and showed that SUMOylation is critical for its ability to repress cone development.

Blackshaw hopes that his basic research results will contribute to translational and clinical research to generate more treatment options for blinding conditions such as macular degeneration, which arise from rod and cone cell death. "Future treatments might be designed to pharmacologically manipulate Pias3-dependent SUMOylation and potentially convert photoreceptors to a cone fate, thus providing a treatment for forms of inherited blindness that selectively result in the death of cone photoreceptors," says Blackshaw.

This research was funded by the National Institutes of Health, the Alfred P. Sloan Foundation, the W.M. Keck Foundation, the Japan Society for the Promotion of Science, and Research to Prevent Blindness.

Authors on the paper are A. Onishi, U. Alexis and S. Blackshaw of the Johns Hopkins University School of Medicine and G. Peng, C. Hsu and S. Chen of the Washington University School of Medicine.


Story Source:

The above story is based on materials provided by Johns Hopkins Medical Institutions. Note: Materials may be edited for content and length.


Journal Reference:

  1. Akishi Onishi, Guang-Hua Peng, Chengda Hsu, Uel Alexis, Shiming Chen, Seth Blackshaw. Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development. Neuron, 2009; 61 (2): 234 DOI: 10.1016/j.neuron.2008.12.006

Cite This Page:

Johns Hopkins Medical Institutions. "Critical Switch In Eye Development Discovered." ScienceDaily. ScienceDaily, 15 March 2009. <www.sciencedaily.com/releases/2009/03/090309162117.htm>.
Johns Hopkins Medical Institutions. (2009, March 15). Critical Switch In Eye Development Discovered. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2009/03/090309162117.htm
Johns Hopkins Medical Institutions. "Critical Switch In Eye Development Discovered." ScienceDaily. www.sciencedaily.com/releases/2009/03/090309162117.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins