Identifying New Drug Targets to Lower Eye Pressure via Outflow

Yutao Liu, MD, PhD
Augusta University Research Institute, Inc. (Augusta, GA)
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2019
Disease:
Glaucoma
Award Amount:
$150,000
Grant Reference ID:
G2016023
Award Type:
Standard
Award Region:
US Southeastern
Yutao Liu, MD, PhD

miR-182 and Trabecular Meshwork Dysfunction in High Tension Glaucoma

Summary

Primary open-angle glaucoma (POAG) is the most common type of glaucoma and lowering eye pressure is the main approach to treating POAG in the clinic. The purpose of this project is to study how a short RNA molecule known as miR-182 may affect the outflow of aqueous humor, which is the clear liquid circulating in the front part of human eyes to bathe its lens and other delicate tissue. We will examine how this short RNA affects eye pressure using an integrative approach. This study may generate therapeutic targets to control eye pressure in human glaucoma patients with high eye pressure.

Details

Our goal is to study how a short RNA molecule called microRNA-182 (miR-182) may affect the exit of the clear liquid in the front part of human eyes (i.e., aqueous humor). Our preliminary studies have indicated that elevated expression of miR-182 may be associated with primary open-angle glaucoma (POAG) with high eye pressure. First, using human ocular cells derived from eye tissue, we will study how the increased expression of miR-182 affects the cellular functions related to the exit of aqueous humor. We will use high throughput RNA sequencing to identify the potential targets of miR-182 in these cells since these targets may play a role in POAG. Second, we will study how the increased expression of miR-182 may affect the secretion of nanoparticles known as exosomes from human ocular cells. We will characterize any potential alterations in the contents of these secreted exosomes, which are secreted directly into the aqueous humor. This project applies an integrative approach by combining multiple experimental technologies to examine the secretion of nanoparticles from glaucoma-related human cells. Successful completion of this comprehensive study will further reveal the role of miR-182 in glaucoma pathogenesis and may provide therapeutic targets for this common eye disorder.

About the Researcher

Yutao Liu, MD, PhD, is an associate professor of Cellular Biology and Anatomy at the Medical College of Georgia, Augusta University, and an adjunct assistant professor of medicine at Duke University School of Medicine. He is an active member of the James and Jean Culver Vision Discovery Institute at Augusta University. His research aims to identify and characterize genetic factors associated with human eye disorders, such as keratoconus and glaucoma. His research has been funded by NIH/NEI, private foundations, and institutional supports. He has been an active Investigator of the NEIGHBORHOOD consortium for glaucoma genetics research since 2010. His research has led to more than 70 peer-reviewed publications. He also enjoys interacting with graduate students and medical students through course lectures and other education-related events.

Personal Story

Originally from China, I trained as a medical doctor in the Department of Nuclear Medicine at Beijing Medical University, Beijing, China. After a few years in clinical practice, I was motivated to discover potential therapies for patients suffering from different disorders. It was during my graduate training in the U.S., that I became fascinated with the genetic aspects of glaucoma.

In 2010, I received the Thomas R. Lee Award from BrightFocus Foundation (previously called American Health Assistance Foundation) to fund my first faculty research project to study the role of a genomic deletion in the GALC gene. Ours was some of the first research to demonstrate that DNA copy number variations (deletions or duplications) have an impact on glaucoma. With my expertise in DNA copy number analysis, and as a co-investigator in the NEIGHBOR glaucoma genetics consortium since 2010, I was able to lead a sub-project on the role of DNA copy number variants in primary open angle glaucoma (POAG). Those results were published in 2014. Research into DNA copy number variants continues to be an important part in my research group. In addition, by establishing our expertise in the area of DNA copy number analysis, BrightFocus funding indirectly but significantly advanced our ability to secure NIH-NEI funding for research into another eye disorder. 

Clearly, support from BrightFocus has been a critical pillar to my academic growth. And now we are very grateful that our newest research project is being supported by BrightFocus Foundation. As background, around 2014, I led a sub-project within the NEIGHBORHOOD consortium to study the contribution of small non-coding RNAs to POAG. We successfully identified a significant association between POAG and a variant in the miR-182 gene, and a potential role for elevated miR-182 expression in glaucoma.

BrightFocus Foundation support will allow us to continue this work in collaboration with Dr. W. Daniel Stamer and Dr. Pedro Gonzalez at Duke University Eye Center. Through it, we hope to describe the molecular mechanisms behind miR-182’s contribution to glaucoma so that potential drug targets can be identified to lower eye pressure.

Without generous donations from donors, we could not make progress in glaucoma genetics. By working together as a community, we are confident that we will be able to identify new therapeutic approaches to treat this common and severe blinding disorder.

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