Federal grant holds promise for macular degeneration and other retinal diseases

A five-year, $2.4 million federal grant will support Buck researchers who hope to develop a “special sauce” that would promote the eye’s ability to heal itself. The new therapy would enhance the use of stem cell-based cell replacement therapies for those suffering from macular degeneration and other retinal-based diseases. And as a bonus, researchers are hoping that the new therapy would slow disease progression so that many patients suffering from macular degeneration would never need to undergo transplantation in the first place.

The work involves a joint project in the Lamba and Jasper labs and focuses on immune modulation to promote a healthy stress response rather than a deleterious inflammatory response to protect neurons in the retina.  

The initial discovery that fueled the project was made in fruit flies in the Jasper lab. Joana Neves, PhD, a postdoctoral research fellow who shares an appointment in both the Jasper and Lamba labs, found that immune cells in the fly secrete a factor that promotes retinal repair in the simple animals. Buck’s Chief Scientific Officer Henri Jasper, PhD, took the discovery to Deepak Lamba, PhD, who is developing stem cell technologies for vision disorders.  Together, they found that mice also secrete this factor and that it promotes retinal repair in three different mouse models of retinal disease.

“Immune modulation helps the eye to repair itself,” said Lamba. “It converts inflammatory immune cells into repairing immune cells.” Lamba explained that inflammatory immune cells often become “bad actors” in the eye because there is not that much debris for the cells to clear up. “These cells get stuck in the inflammatory state, causing degeneration and creating a less-than-optimal environment for stem cell-based replacement therapies.”    

That less-than-ideal environment in the retina causes real problems. Even though researchers around the world have successfully transplanted retinal stem cells in mice, that success has not benefited the millions of people who suffer from vision problems related to retinal degeneration. Lamba says that’s because only about 1% of the transplanted cells survive over time.  “There are many roadblocks that stand in the way of successful transplantation,” said Lamba. “Hopefully therapies that involve immune modulation will turn that statistic around by creating a welcoming niche for the transplanted retinal stem cells.”

Both Lamba and Jasper are excited about the larger potential of immune modulation in regenerative medicine. “Our best hope is that we can develop therapies that can be used early in the disease process so that the eye can repair itself before serious symptoms become an issue,” said Jasper. “This could be a game-changer when it comes to treating retinal degeneration.”

The project highlights the power of the Buck’s collaborative research environment.  There are not many places where a fruit fly geneticist can easily take a discovery to someone who is developing stem cell- based treatments for retinal diseases. It further highlights the benefits of a focus on collaborative work by the newly renewed ‘Glenn Center for Biology of Aging Research at the Buck Institute’. Neves was and is funded by the Glenn Foundation for Medical Research, and the fact that the two faculty members were able to hire a joint postdoc allowed them to fast-track the project. She led the project from its 

inception through development and execution, and collaborated with members of both labs to establish the crucial findings that served as preliminary data for the new grant. 

The work also emphasizes the value of Buck’s basic research in simple organisms like the fruit fly. “That early work in the fly allowed us to identify genes that led us to an immune modulator that is conserved among many species,” said Jasper.  “We were able to do that work relatively quickly at a low cost and it helped us set up the work that is now taking place in mice and human cells.”  Jasper added, “Don’t discount the relevance of the fruit fly when it comes to studying human disease. We have more in common with them than most people appreciate.” 

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