The Role of Long Non-Coding RNAs in HTRA1 Regulation

Michael Farkas, PhD
The Research Foundation for SUNY on behalf of University at Buffalo Sponsored Projects Services (Buffalo, NY)
Year Awarded:
2019
Grant Duration:
July 1, 2019 to June 30, 2021
Disease:
Macular Degeneration
Award Amount:
$200,000
Grant Reference ID:
M2019108
Award Type:
Standard
Award Region:
US Northeastern
Michael Farkas, PhD

Defining the Functional Role of RPE-Expressed AMD Risk-Associated Long Non-Coding RNAs

Summary

We aim to elucidate the role two novel long non-coding RNAs play in the regulation of HTRA1, a gene associated with high risk of developing AMD. The long non-coding RNAs are predicted, and our data demonstrates, to decrease HTRA1 levels. The data obtained in this proposal will be used to advance our knowledge of AMD pathogenesis, and ultimately, toward a therapeutic intervention.

Details

The goal of our project is to study the expression and function of two novel long non-coding RNAs (lncRNAs) that are located in the HTRA1/ARMS2 risk loci. We hypothesize that these novel lncRNAs control the expression of ARMS2 and HTRA1, and this expression is affected in individuals with AMD.  We will test this hypothesis by studying the expression of the novel lncRNAs in the retina from AMD-affected donor eyes and compare this expression to normal donor eyes. Bioinformatic analysis of the novel lncRNAs suggests they are processed into short interfering RNAs, which are known to repress gene expression. We will test their function by over-expressing them in induced pluripotent stem cell-derived retinal pigment epithelial cells and quantify the change in expression of HTRA1 and ARMS2.

This study is unique in that it is the first to identify the expression of lncRNAs in any of the AMD risk loci. Since none of the protein-coding genes have been proven to be causative for AMD pathogenesis, this study will begin to shed light on the role played by non-coding RNAs.

About the Researcher

Michael Farkas is an Assistant Professor of Ophthalmology at the State University of New York at Buffalo.  He trained at the F.M. Kirby Center for Molecular Ophthalmology at the University of Pennsylvania and the Ocular Genomics Institute at the Massachusetts Eye and Ear and Harvard Medical School.  The focus of his research is to study the causes of and treatments for vision loss. Specifically, his interests lie in the function of long non-coding RNAs and how they either cause disease or could be used for treatment. In addition to the aims of this study, he is also studying the role of lncRNAs for developing transplantable RPE to be used as a treatment for AMD.

Personal Story

I would first like to thank the donors, the BrightFocus Foundation, and the reviewers for their support.  This is especially meaningful to me because lncRNAs are understudied in the retina, in both normal and disease cases.  BrightFocus Foundation was the first to recognize its importance. I hope that our research provides meaningful insights into the pathogenesis AMD, and stimulates lncRNA research in vision as a whole.

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