The Role of Microglia Activation in Retinal Ganglion Cell Degeneration

Christopher Kai-shun Leung, MD
The Chinese University of Hong Kong (Hong Kong, China)
Year Awarded:
2011
Grant Duration:
July 1, 2011 to June 30, 2013
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2011007
Award Type:
Standard
Award Region:
International

Role of CX3CR1 in Microglia Activation and Retinal Ganglion Cell Degeneration in Glaucoma - An in Vivo Imaging Study

Summary

This study is designed to address the role of microglia activation in relation to retinal ganglion cell degeneration by directly visualizing the interaction between microglia and RGCs with live imaging with confocal scanning laser ophthalmoscopy in experimental glaucoma. We investigate if knocking out the CX3CR1 gene, a gene implicated in mediating the communication between retinal ganglion cells and microglia, could reduce the activation of microglia and enhance the survival of retinal ganglion cells in glaucoma.

Details

Physical changes happen to the retina during glaucoma. However, these changes can be too small to see with a magnifying device in an eye doctor's office. Dr. Christopher Kai-shun Leung and collaborators will use a machine, called a confocal laser scanning ophthalmoscope, to take live pictures of the retinas in mice before and after they've been given glaucoma through increasing their eye pressure. They suspect that immune cells of the retina, called microglia, could promote damage to retinal neurons. To track their activity, they will specifically make these cells glow in the dark. This is the first study to use live imaging to directly examine the interactions between retinal neurons and microglial cells in glaucoma. In the future, the results from this study could be used to design drugs to prevent the damage to the retina caused by microglia.

Research Updates

With the objective of investigating the impact of microglia activation on retinal ganglion cell degeneration in glaucoma, Dr. Leung’s team has successfully engineered mice that can allow direct visualization of both microglial and retinal ganglion cells, as well as their interaction. They have collected preliminary baseline data regarding the density (number) and the morphology (shape) of microglial and retinal ganglion cells in the retinas of normal healthy animals. The team will then analyze these same changes to the cells in animals with glaucoma. A comparison of the results will allow the team to determine the role of CX3CR1, a gene that is implicated in mediating the communication between retinal ganglion cells and microglia. Therefore, Cx3CR1 could be a potential therapeutic target to enhance retinal ganglion cell survival in glaucoma.

About the Researcher

Dr. Christopher Leung is Associate Professor of the Department of Ophthalmology & Visual Sciences, the Chinese University of Hong Kong (CUHK). He completed clinical and research fellowship training at the Hamilton Glaucoma Center of the University of California, San Diego. He is a clinician-scientist with research interest in retinal nerve fiber layer and retinal ganglion cells imaging. Among his research awards include Hong Kong Medical Association Prize, National Best Paper on Prevention of Blindness in the World Ophthalmology Congress 2006, Schanzlin Research Award, World Glaucoma Association Science Award – the Promise, AAO Achievement Award, ARVO/Alcon Clinician-Scientist Research Award and the APAO Nakajima Award. Dr Leung currently serves on the Associate Advisory Board of the World Glaucoma Association (WGA), and as reviewer of over 20 peer-reviewed journals in ophthalmology and visual sciences.