Small RNAs as signaling molecules between the RPE and choroid

Jiyang Cai, PhD
Vanderbilt University (Nasville, TN)
Year Awarded:
2012
Grant Duration:
July 1, 2012 to June 30, 2015
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2012012
Award Type:
Standard
Award Region:
International

Exosomal microRNA from the RPE

Summary

Interactions between the retinal pigment epithelium (RPE,) the cell layer that nourishes and detoxifies the retina, and their underlying choroidal blood vessels are critical in maintaining the structure and functions of the outer retina. Dr. Jiyang Cai and colleagues are examining how RPE cell delivery bubbles (called microvesicles) can transfer genetic materials to the choroidal blood vessel cells and alter their functions. Results from this study could reveal a new cause of age-related macular degeneration (AMD).

Details

Dr. Jiyang Cai and colleagues will use integrated genetics tools to study animals engineered to have age-related macular degeneration (AMD). Specifically for this project, they are investigating the hypothesis that the RPE and blood vessel cells communicate with each other by transferring small genetic fragments (called microRNAs) that then change the functions of the recipient cells.

Recent studies suggest that not only are there problems with the RPE, but that the choroidal blood vessels underneath the RPE also degenerate early in AMD. The RPE and the choroidal endothelial cells are separated by a thin barrier known as Bruch's membrane. It is unclear what signals are exchanged between the two types of cells and how their normal communication is interrupted during early AMD. Preliminary work completed by this research group has shown that microvesicles released from the RPE contain various small RNA fragments. The proposed studies will further examine how stress conditions related to AMD may change the content of these RPE microvesicles that, in turn, may alter functions of the choroidal endothelial cells.

This proposal will use various innovative approaches, such as a new mouse engineered to have AMD and a technique called high throughput gene array. Cai is studying a mechanism that accounts for the early dysfunction of RPE and choroid—perhaps chronic oxidative injury is a major factor of RPE degeneration and dry AMD. The results from this research could lead to a new AMD treatment with emphasis on strengthening the protection and repair mechanisms of the RPE. Hopefully, this can be achieved by target-based nutritional intervention combined with a healthy lifestyle.