Neurotrophins in High-tension Glaucoma

Xiaorong Liu, PhD
Northwerstern University (Evanston, IL, United States)
Year Awarded:
2011
Grant Duration:
July 1, 2011 to June 30, 2014
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2011033
Award Type:
Standard
Award Region:
US Midwestern

Co-principal Investigators

Liang Feng, PhD
Northwestern University
Recipient of the Dr. Douglas H. Johnson award for glaucoma research

Neurotrophic Mechanisms in Ocular Hypertension Mice

Summary

Our primary goal is to investigate how BDNF and NT-3 protect ganglion cells and visual function against IOP elevation. By combining transgenic mouse systems with laser-induced model of OHT, our experimental design allows neurotrophin signaling to be manipulated in vivo and the glaucomatous condition to be achieved at the same time. The results obtained from these experiments will reveal the roles of neurotrophin signaling in shaping retinal structure and visual function in glaucoma.

Details

A group of nerve survival factors, called neurotrophins, will be tested in a mouse model of glaucoma to see if they can rescue the structure and function of the optic nerve cells before their death. Dr. Xiaorong Liu and colleagues will use mice with high eye pressure to mimic the human high-tension glaucoma in their tests. They will use genetic techniques to specifically examine how two neurotrophins—called BDNF and NT- 3—contribute to protect retinal cell structure and visual behaviors in mice with high eye pressure. The results will thus provide insight into whether BDNF and NT-3 are good candidates for drug targeting to prevent the optic nerve cell damage that occurs in glaucoma.

Research Updates

The long-term goal of this proposal is to test whether neurotrophins, a group of nerve survival proteins, can rescue the structure and function of the optic nerve cells before their death in a mouse model of glaucoma. Drs. Liu’s and Liang Feng’s team used mice with high eye pressure to mimic the human high-tension glaucoma in their tests. They have successfully established a laser-induced mouse model of ocular hypertension and further showed that the optic nerve cell degeneration is location- and subtype-dependent. Using a visual behavioral test, the team found a decrease in visual acuity (sharpness) and contrast sensitivity in mice with ocular hypertension. Their study introduces a new model system to investigate how the destruction of optic nerve cells leads to visual impairments in glaucoma patients. Next, they will use genetic techniques to specifically examine how two neurotrophins—called BDNF and NT-3—help protect retinal cell structure and the related visual behaviors in mice with high eye pressure. The results will provide insight into whether BDNF and NT-3 are good candidates for drug targeting to prevent the optic nerve cell damage that occurs in glaucoma.

About the Researcher

Dr. Liu is a Research Assistant Professor in the Department of Neurobiology and Physiology at the Northwestern University. She completed her doctoral studies at the University of Virginia Charlottesville and her postdoctoral research at the University of California San Francisco. Dr. Liu's laboratory focuses on understanding the regulation and misregulation of neural structures and functions in normal and diseased retinas. Her research team is investigating how neurotrophins, the survival factors of neurons, modulate the normal development of mouse retinal ganglion cells and protect their structure and functions in glaucoma.

Publications

Feng, L., Chen, H., Suyeoka, G., Cang, J. and Liu, X. (2013) A Laser-induced Mouse Model of Chronic Ocular Hypertension to Characterize Visual Defects J Vis Exp (accepted)

Feng, L.,  Zhao, Y., Yoshida, M.,  Chen, H., Yang, J.F., Kim, T.S., Cang, J., Troy, J.B. and Liu, X. (2013) Sustained Ocular Hypertension Induces Dendritic Degeneration of Mouse Retinal Ganglion Cells that Depends on Cell-type and Location. Invest Ophthalmol Vis Sci (revision).