Understanding how connections between cells facilitate disease

John O'Brien, PhD
The University of Texas Health Science Center at Houston (Houston, TX)
Year Awarded:
2006
Grant Duration:
April 1, 2006 to March 31, 2009
Disease:
Macular Degeneration
Award Amount:
$200,000
Grant Reference ID:
M2006025
Award Type:
Standard
Award Region:
US Southern

Physiological Uncoupling of Cone Gap Junctions

Summary

This project will examine the physiological mechanisms that close cone to cone 'gap junctions', preventing spread of cell death. The investigators will use these studies to identify the signaling pathways that change the functional state of cone gap junctions in order to develop pharmacological interventions that close the junctions, reducing the exchange of small molecules between photoreceptors.

Details

Photoreceptors are joined to each other by gap junctions, channels that permit exchange of small molecules between adjacent cells. During cell death, such as occurs in macular degeneration, death-promoting factors may pass through gap junctions to adjacent cells and trigger death in otherwise healthy adjacent photoreceptors. This process can speed the progression of disease and hasten vision loss. Treatments that close these gap junctions may delay the progression of disease. This project will examine the physiological mechanisms that close cone-cone gap junctions. By studying biochemical properties of the cone photoreceptor gap junction protein, connexin35, we can estimate the functional state of the gap junctions. We will now use these studies to identify the signaling pathways that change the functional state of cone gap junctions. This information will be used to develop pharmacological interventions to close cone gap junctions, reducing the exchange of small molecules between photoreceptors. It is hoped that these studies will identify drugs that can be used to close cone gap junctions selectively. Such drugs could provide a treatment strategy that is complementary to existing treatments for macular degeneration by reducing the rate at which the degeneration spreads.

Don't miss out.
Receive research updates, inspiring stories, and expert advice
Please enter your first name.
Please enter your last name.
Keep me informed about: *
Please select at least one.
You must select at least one disease category.