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A recently awarded $1.5 million听grant from the U.S. 鈥檚 (NIH) will support ongoing research into retinal degenerative diseases led by , a professor in the molecular, cellular and biomedical sciences department and the director of the Center of Integrated Biomedical and Bioengineering Research (CIBBR) at 91制片厂. This latest grant extends three decades of continuous funding from NIH to support Cote鈥檚 research program examining the visual signaling pathways in rod and cone photoreceptor cells that are responsible for the very first events in the vision process.

has long studied the visual signaling pathway鈥檚 central enzyme, called (PDE6), including how this enzyme is activated by light and subsequently how it returns to its dark-adapted state. The current grant supports research into determining the atomic-level structure of PDE6, as well as the activating and inactivating proteins that bind to PDE6 during visual signaling. This structural knowledge of PDE6 and its binding partners is critical for improving our ability to predict whether genetic mutations of PDE6 and/or the proteins that regulate PDE6 are likely to cause visual disorders or blindness.

鈥淓ach of us has a multitude of mutations in our genes, and many of these mutations are silent or benign,鈥� described Cote. 鈥淲e鈥檙e trying to predict which mutations in PDE6 are pathogenic and prevent the visual signaling pathway from responding properly to light, ultimately leading to rod photoreceptor cell death and the progressive degeneration of the entire retina.鈥�

"We鈥檙e trying to predict which mutations in PDE6 are pathogenic and prevent the visual signaling pathway from responding properly to light, ultimately leading to rod photoreceptor cell death and the progressive degeneration of the entire retina."

Cote鈥檚 current research focuses on understanding the molecular defects that cause , an inherited retinal degenerative disease that typically presents symptoms that begin in childhood or early adulthood and can result in total blindness. Approximately 1 in 3,500 people in the United States have the disease.

鈥淥ne of the things that distinguishes retinitis pigmentosa from other blinding diseases is that the onset of symptoms occurs in late childhood or adolescence, and are not apparent at birth,鈥� said Cote. 鈥淭he vision of a person with retinitis pigmentosa begins to deteriorate as they age, starting with night blindness (an inability to see at night), a gradual loss of peripheral vision and eventually total or near-total blindness.鈥�

With the advent of inexpensive DNA sequencing technologies, people at risk of inheriting retinitis pigmentosa or related eye diseases鈥攐r children starting to display loss of visual function鈥攃an have their genome sequenced to determine whether they harbor pathogenic mutations in the rod and cone PDE6 genes.

鈥淕enetic screening of at-risk individuals will allow us to intervene early on with treatments鈥揵efore their vision deteriorates 鈥� and hopefully prevent the degenerative process,鈥� said Cote.

Therapeutic treatments may take the form of administering drugs that can preserve photoreceptor function or use gene editing to permanently correct the mutation. By mapping known PDE6 mutations to the enzyme鈥檚 three-dimensional structure, Cote鈥檚 lab will improve our ability to distinguish pathogenic from harmless mutations and give ophthalmologists greater precision in diagnosing and treating retinal diseases.

You can learn more about Cote鈥檚 research on his .