Inflammation as a Trigger of Age Related Macular Degeneration

Bruce Ksander, PhD
The Schepens Eye Research Institute (Boston, MA, United States)
Year Awarded:
2011
Grant Duration:
July 1, 2011 to June 30, 2013
Disease:
Macular Degeneration
Award Amount:
$99,836
Grant Reference ID:
M2011069
Award Type:
Standard
Award Region:
US Northeastern

NALP3 Activation Triggers Development of AMD

Summary

Age related Macular Degeneration (AMD) causes loss of vision and blindness in elderly patients when two types of cells are damaged (i) RPE (called retinal pigment epithelial cells), and (ii) photoreceptors. We discovered a gene (called NALP3) is expressed in retinal cells during development of AMD. We predict this gene is important in triggering this disease via the activation of localized inflammation.

Details

Retinal pigment epithelial (RPE) cells support the light‐detecting photoreceptor cells by recycling and removing waste products. If RPE cells are unhealthy, then this waste can build‐up and damage the retina. Inflammation is an important part of the AMD disease process, and RPE cells have their own special type of proteins—called the “inflammasome”—to monitor and determine if the RPE are working properly. In fact, if this RPE waste recycling and removal process isn't functioning properly, the inflammasome sends out signals for the immune system to swoop in and kill the malfunctioning RPE cells. Dr. Ksander and collaborators have discovered a new risk gene—called NALP3— that is expressed in retinal cells and is suspected to be important in triggering AMD via the inflammasome. These researchers will determine whether this gene is involved in the death of RPE cells and, if so, whether it will be a new target for treatment of AMD.

Publications

Tseng WA, Thein T, Kinnunen K, Lashkari K, Gregory MS, D'Amore PA, Ksander BR. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013 Jan 7;54(1):110-20. doi: 10.1167/iovs.12-10655. PubMed Icon Google Scholar Icon