National Glaucoma Research
Shunbin Xu, M.D., Ph.D.
Rush University Medical Center
Chicago, IL, United States
Title: MicroRNAs in Glaucomatous Neurodegeneration
Non-Technical Title: microRNAs in glaucoma
Acknowledgements: Recipient of the Thomas R. Lee award for National Glaucoma Research.
Duration: July 1, 2011 - March 31, 2014
Award Type: Standard
Award Amount: $100,000
- microRNAs are newly recognized regulators of gene expression, playing important roles in both normal functions and diseases in almost all organ systems.
- Glaucoma is the result of malfunction and death of retinal ganglion cell.
- This research will identify the microRNAs involved in the malfunction and death of retinal ganglion cells during the development of glaucoma, which may be novel therapeutic targets for the treatment of the disease.
There are recently discovered gene-expression controllers—called microRNAs—that play important roles in both health and disease. However, the roles that microRNAs play in glaucoma are completely unknown. Dr. Shunbin Xu and colleagues plan to use mice that have human-like glaucoma to gather microRNAs from the "optic nerve head," a region often first affected during glaucoma development. By comparing the presence and activities of different microRNAs at various stages of disease in the optic nerve head, they will discover those that change in correlation with the start and progression of the disease. These microRNAs may be used as new drug targets for the prevention and treatment of glaucoma.
MicroRNAs (miRNAs) are gene-expression controllers that play important roles in health and disease. However, their role in glaucoma remains unclear. This project uses mice with human-like glaucoma as a source of miRNAs from the retina and the optic nerve head, often the region first affected in glaucoma. Dr. Xu’s team is identifying those miRNA that change their activity at the start and during the progression of the disease. Ultimately, knowing their identities may translate into new drug targets for the prevention and treatment of glaucoma. Since receiving funding, the team has made progress, as follows:
They isolated total retinal RNA from glaucoma mice and their age-matched controls. The three stages of disease development on which they focused their studies were: four months, where the mice are pre-glaucoma with intraocular pressure (IOP) near or below the colony average; eight months, shortly after the onset of detectable glaucoma with elevated IOPs; and twelve months,, with further glaucoma development and elevated IOP. After further analysis, the team found that approximately 400 miRNAs are expressed in the retina of the glaucoma mouse and normal controls at all three ages (four, eight and twelve months old).
The team then compared these miRNA profiles and identified a series of miRNAs whose expression levels change in the glaucoma mice, but not in the normal controls. This is the first time that it has been reported that miRNAs are involved in the development of glaucoma. They also identified a series of miRNAs that are differentially expressed in the retina of different ages in both glaucoma and normal controls, suggesting that miRNAs are involved in normal retinal aging as well as glaucoma. They completed a further study that showed some of the differentially-expressed miRNAs may regulate other key proteins known to cause degeneration of retinal ganglion cells and play important roles in glaucoma.
The miRNAs identified by Dr. Xu’s team may serve as targets for new treatments. The team also established in this first year the methodology to isolate and identify miRNAs in optic nerve heads, which will help with future identification of additional miRNAs involved in early glaucoma.
Dr. Shunbin Xu, M.D./Ph.D. is an Assistant Professor of Ophthalmology and Neurological Sciences at Rush University Medical University. Dr. Xu obtained his medical doctor degree at the Peking Union Medical College and his Ph.D. degree in Human Genetics and Molecular Biology at the Johns Hopkins University. Dr. Xu completed his postdoctoral studies on retinal and neurodevelopment and stem cells at the University of Toronto. At Rush, Dr. Xu's laboratory focuses on microRNAs in normal development and functions of the retina and neurological systems, as well as in retinal and neurological diseases. His team is heavily involved in discovering new therapeutic targets and early diagnostic biomarkers for the treatment of retinal and neurological diseases, including glaucoma, diabetic retinopathy, Age-related macular degeneration and Parkinson's disease. Dr. Xu's work has been supported by the Glaucoma Research Foundation, the Juvenile Diabetes Research Foundation, Lincy foundation, and the Michael J. Fox Foundation. In addition, Dr. Xu is the director of the microRNA and Gene Expression of Core of the Rush University Translational Sciences Consortium.