The Role of MicroRNAs in Regulating Aqueous Humor Outflow
The most effective therapy for glaucoma is reducing eye pressure, but it is not understood how the pressure in the eye is regulated. MicroRNAs (miRNAs) are very small genetic sequences that can regulate the expression of many genes. In fact, a single miRNA is so powerful that it can modulate several genes. The aim of this project is to understand the role of a very important miRNA in regulating intraocular pressure (IOP). This may be a very effective new way to treat elevated eye pressure in glaucoma.
Primary open angle glaucoma (POAG) is an irreversible eye blinding disease. Schlemm’s canal (SC) inner wall and juxtacanalicular (JCT) tissue are thought to be the sites of major aqueous outflow resistance, which is responsible for elevated eye pressure characteristic of many cases of POAG. Therefore it is important to understand how SC cells regulate eye pressure. Our early work suggest that miRNAs participate eye pressure regulation, it this project we will use molecular biology and pharmacology techniques to understand the mechanism of such regulations. This work might pave the way to the discovery of a new pathway that controls IOP.
About the Researcher
The principal investigator, Yuan Lei, PhD, is well trained in the field of aqueous humor outflow physiology. She did her postdoctoral training with Prof. CR Ethier and Prof. WD Stamer, and has worked in the area of anterior segment aqueous humor outflow physiology since 2008. Dr. Lei was the first to report a method for isolating, culturing and characterizing porcine angular aqueous plexus cells (AAP) cells (ie, the human equivalent of Schlemm’s canal endothelial cells). She also set up the first mouse eye perfusion rig in Prof. Ethier's laboratory and is very experienced with this technique. Dr. Lei has made significant contributions to the understanding of aqueous humor outflow physiology and the role of eNOS signaling pathway in regulating intraocular pressure. In this field, the applicant has published 11 first or corresponding author papers in IOVS and ACS Applied Materials and Interfaces.
I decided to do a PhD in glaucoma because my grandmother and my father both suffered from this disease. I have seen how glaucoma gradually affected the vision of my family members, and there is not a real cure for it. As a glaucoma patient, one is expected to take pressure-lowering drugs for life, but current medication cannot always lower the eye pressure enough to the desired level. From our earlier work, we identified a special microRNA (miRNA) from high throughput data that is relevant to eye pressure regulation. Although miRNAs are very small genetic sequences, they are so very powerful that a single miRNA can modulate several genes. We hope that by using this miRNA tool, we can target several important genetic pathways at the same time that lead to high eye pressure, and therefore preserve eyesight of glaucoma patients.
Hu C, Sun J, Zhang Y, Chen J, Lei Y, Sun X, Deng Y. Local Delivery and Sustained-Release of Nitric Oxide Donor Loaded in Mesoporous Silica Particles for Efficient Treatment of Primary Open-Angle Glaucoma. Adv Healthc Mater. 2018 Dec;7(23):e1801047. doi: 10.1002/adhm.201801047. Epub 2018 Nov 2. PubMed PMID: 30387326
First published on: July 27, 2018
Last modified on: June 30, 2020